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  • 1.
    Bajraktari, Gani
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Clinic of Cardiology and Angiology, University Clinical Centre of Kosova, Prishtina, Republic of Kosovo.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Clinic of Cardiology and Angiology, University Clinical Centre of Kosova, Prishtina, Republic of Kosovo.
    Jashari, Fisnik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Clinic of Cardiology and Angiology, University Clinical Centre of Kosova, Prishtina, Republic of Kosovo.
    Schmermund, Axel
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Coronary calcium score correlates with estimate of total plaque burden2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 167, no 3, p. 1050-1052Article in journal (Refereed)
  • 2.
    Bengrid, Tarek
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zhao, Ying
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Capital Med Univ, Beijing Anzhen Hosp, Dept Ultrasound, Beijing, Peoples R China.
    Schmermund, Axel
    Bethanien Hosp, Frankfurt, Germany.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Coronary calcium score is superior to exercise tolerance testing in predicting significant coronary artery stenosis2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 2, p. 1697-1699Article in journal (Refereed)
  • 3.
    Djekic, Demir
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Novo, Mehmed
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Metabolomics in atherosclerosis2015In: International Journal of Cardiology Metabolic & Endocrine, E-ISSN 2214-7624, Vol. 8, p. 26-30Article in journal (Refereed)
    Abstract [en]

    It is well established that atherosclerotic cardiovascular disease (ACD) is a leading cause of death in the West. There are several predisposing factors for ACD, which can be divided into two groups: firstly modifiable risk factors, including hypertension, dyslipidaemia, type 2 diabetes mellitus, obesity, smoking and a sedentary lifestyle and secondly the unmodifiable risk factors such as age, gender and heredity. Since single biomarkers are unable to provide sufficient information about the biochemical pathways responsible for the disease, there is a need for a holistic approach technology, e.g. metabolomics, that provide sufficiently detailed information about the metabolic status and assay results will be able to guide food, drug and lifestyle optimisation. Rather than investigating a single pathway, metabolomics deal with the integrated identification of biological and pathological molecular pathways. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy are the two most commonly used techniques for metabolite profiling. This detailed review concluded that metabolomics investigations seem to have great potential in identifying small groups of disturbed metabolites which if put together should draw various metabolic routs that lead to the common track pathophysiology. The current evidence in using metabolomics in atherosclerotic cardiovascular disease is also limited and morewell designed studies remain to be established, which might significantly improve the comprehension of atherosclerosis pathophysiology and consequently management.

  • 4.
    Henein, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bengrid, Tarek
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zhao, Y.
    Ultrasound Department, Capital Medical University, Beijing, China.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schmermund, A.
    Medicine, Bethanien Hospital, Frankfurt, Germany.
    Extensive coronary calcification compromises myocardial perfusion in the absence of high grade stenosis2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E68-E68Article in journal (Other academic)
  • 5.
    Henein, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schmermund, A.
    Diederichsen, A. C. P.
    Mickley, H.
    Zamorano, P.
    Gueret, P.
    Budoff, M. J.
    European Calcific Coronary Artery Disease (Euro-CCAD) study: the additional value of coronary calcification, to angiography, in investigating angina patients2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no Supplement: 1, p. 177-177Article in journal (Other academic)
    Abstract [en]

    Background and aim: This study is a part of the Euro-CCAD (CalcificCoronary Artery Disease) project, investigating the geographic prevalence of a coronary artery calcium (CAC) score of >400 in patients with no flow-limiting lesions (FLL) as a potential cause for stable angina. With the development of computerized tomographic coronaryangiography (CTCA), assessment of CAC has become less fashionable, although CTCA often fails to determine the exact cause of symptoms in the absence of FLLs.

    Methods: Data from consecutive symptomatic intermediate risk patients (as defined by guidelines), who had both CA and calcium scoring, were compared between USA and Europe as well as between Europeancountries (Denmark, Germany, France and Spain). No patient had a priorcoronary event, intervention, valve disease or kidney failure.

    Results: The inclusion criteria were fulfilled in 4,444 patients, (60% males), mean age 59.3 years (SD 11.3 years). The prevalence of FLL was higher in the USA at 53% (983/1851) than in Europe at 34% (870/2593) as a whole, (p<0.001). The FLL prevalence was also different (p<0.001) within Europe: Denmark 16%, Germany 35%, France 46% and Spain 89%. In patients with no FLL, 9% had CAC >400, with no difference in prevalence between the USA and Europe, irrespective of age and gender. However, within Europe the prevalence of patients without FLL and with a CAC score >400 differed: Spain 22%, Germany 13%, France 10% and Denmark 7%. Within the total patient population 22% of those with CAC score >400 had no FLL.

    Conclusion: Despite the known variability in the current management of symptomatic angina patients at intermediate risk between the USA andEuropean countries, a consistent proportion (nearly 10%) exhibits severe CAC in the absence of flow limiting lesions. The presence of severe CAC could explain their symptoms through compromised coronary flow reserve. These results highlight the potential value of obtaining additional anatomical information by using CAC assessment in symptomatic patients.

  • 6.
    Henein, Michael Y.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bengrid, Tarek
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Zhao, Ying
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schmermund, Axel
    Coronary calcification compromises myocardial perfusion irrespective of luminal stenosis2017In: IJC HEART & VASCULATURE, ISSN 2352-9067, Vol. 14, p. 41-45Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to evaluate the relationship between coronary artery calcification (CAC) assessed by multi-detector computed tomography (MDCT) and myocardial perfusion assessed by cardiac magnetic resonance imaging (CMR) in a group of symptomatic patients. Method: Retrospective analysis of 120 patients (age 65.1 +/- 8.9 years, 88 males) who presented with atypical chest pain to Bethanien Hospital, Frankfurt, Germany, between 2007 and 2010 and who underwent CAC scoring using MDCT, CMR, and conventional coronary angiography. Patients were divided into those with high-grade (HG) stenosis (n = 67, age 65.1 +/- 9.4 years) and those with no-HG stenosis (n = 53, age 65.1 +/- 8.6 years). Results: There were more males with HG stenosis (82.1% vs. 62.3%, p = 0.015), in whom the percentage and number of abnormal perfusion segments were higher at rest (37.3% vs. 17%, p = 0.014) but not different with stress (p = 0.83) from those with no-HG stenosis. Thirty-four patients had myocardial perfusion abnormalities at rest and 26 patients developed perfusion defects with stress. Stress-induced myocardial perfusion defects were 22.4% sensitive and 79.2% specific for detecting HG stenosis. The CAC score was lower in patients with no-HG stenosis compared to those with HG stenosis (p < 0.0001). On the ROC curve, a CAC score of 293 had a sensitivity of 71.6% and specificity of 83% in predicting HG stenosis [(AUC 0.80 (p < 0.0001)]. A CAC score of 293 or the presence of at least 1 segment myocardial perfusion abnormality was 74.6% sensitive and 71.7% specific in detecting HG stenosis, the respective values for the 2 abnormalities combined being 19.4% and 90.6%. The severity of CAC correlated with the extent of myocardial perfusion in the patient group as a whole with stress (r = 0.22, p = 0.015), particularly in those with no-HG stenosis (r = 0.31, p = 0.022). A CAC score of 293 was 31.6% sensitive and 87.3% specific in detecting myocardial perfusion abnormalities. Conclusion: In a group of patients with exertional angina, coronary calcification is more accurate in detecting high-grade luminal stenosis than myocardial perfusion defects. In addition, in patients with no stenosis, the incremental relationship between coronary calcium score and the extent of myocardial perfusion suggests coronary wall hardening as an additional mechanism for stress-induced angina other than luminal narrowing. These preliminary findings might have a clinical impact on management strategies of these patients other than conventional therapy.

  • 7.
    Henein, Michael Y.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Schmermund, A.
    Diederichsen, A. C. P.
    Mickley, H.
    Zamorano, P.
    Gueret, P.
    Budoff, M. J.
    European Calcific Coronary Artery Disease (Euro-CCAD) study: the relationship between coronary calcification and flow limiting lesion in symptomatic patients2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no Supplement: 1, p. 723-723Article in journal (Other academic)
    Abstract [en]

    Background and aim: This study is a part of the Euro-CCAD (CalcificCoronary Artery Disease) project, investigating the geographic prevalence of a coronary artery calcium (CAC) score of >400 in patients with no flow-limiting lesions (FLL) as a potential cause for stable angina. With the development of computerized tomographic coronaryangiography (CTCA), assessment of CAC has become less fashionable, although CTCA often fails to determine the exact cause of symptoms in the absence of FLLs.

    Methods: Data from consecutive symptomatic intermediate risk patients (as defined by guidelines), who had both CA and calcium scoring, were compared between USA and Europe as well as between Europeancountries (Denmark, Germany, France and Spain). No patient had a priorcoronary event, intervention, valve disease or kidney failure.

    Results: The inclusion criteria were fulfilled in 4,444 patients, (60% males), mean age 59.3 years (SD 11.3 years). The prevalence of FLL was higher in the USA at 53% (983/1851) than in Europe at 34% (870/2593) as a whole, (p<0.001). The FLL prevalence was also different (p<0.001) within Europe: Denmark 16%, Germany 35%, France 46% and Spain 89%. In patients with no FLL, 9% had CAC >400, with no difference in prevalence between the USA and Europe, irrespective of age and gender. However, within Europe the prevalence of patients without FLL and with a CAC score >400 differed: Spain 22%, Germany 13%, France 10% and Denmark 7%. Within the total patient population 22% of those with CAC score >400 had no FLL.

    Conclusion: Despite the known variability in the current management of symptomatic angina patients at intermediate risk between the USA andEuropean countries, a consistent proportion (nearly 10%) exhibits severe CAC in the absence of flow limiting lesions. The presence of severe CAC could explain their symptoms through compromised coronary flow reserve. These results highlight the potential value of obtaining additional anatomical information by using CAC assessment in symptomatic patients.

  • 8.
    Henein, Michael Y
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Zhao, Ying
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Sun, Lin
    Khir, Ashraf W
    Franklin, Karl
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The human heart: application of the golden ratio and angle2011In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 150, no 3, p. 239-242Article in journal (Refereed)
    Abstract [en]

    The golden ratio, or golden mean, of 1.618 is a proportion known since antiquity to be the most aesthetically pleasing and has been used repeatedly in art and architecture. Both the golden ratio and the allied golden angle of 137.5° have been found within the proportions and angles of the human body and plants. In the human heart we found many applications of the golden ratio and angle, in addition to those previously described. In healthy hearts, vertical and transverse dimensions accord with the golden ratio, irrespective of different absolute dimensions due to ethnicity. In mild heart failure, the ratio of 1.618 was maintained but in end-stage heart failure the ratio significantly reduced. Similarly, in healthy ventricles mitral annulus dimensions accorded with the golden ratio, while in dilated cardiomyopathy and mitral regurgitation patients the ratio had significantly reduced. In healthy patients, both the angles between the mid-luminal axes of the pulmonary trunk and the ascending aorta continuation and between the outflow tract axis and continuation of the inflow tract axis of the right ventricle approximate to the golden angle, although in severe pulmonary hypertension, the angle is significantly increased. Hence the overall cardiac and ventricular dimensions in a normal heart are consistent with the golden ratio and angle, representing optimum pump structure and function efficiency, whereas there is significant deviation in the disease state. These findings could have anatomical, functional and prognostic value as markers of early deviation from normality.

  • 9.
    Ibrahimi, Pranvera
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Jashari, Fisnik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bajraktari, Gani
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Coronary and carotid atherosclerosis: how useful is the imaging?2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 231, no 2, p. 323-333Article in journal (Refereed)
    Abstract [en]

    The recent advancement of imaging modalities has made possible visualization of atherosclerosis disease in all phases of its development. Markers of subclinical atherosclerosis or even the most advanced plaque features are acquired by invasive (IVUS, OCT) and non-invasive imaging modalities (US, MRI, CTA). Determining plaques prone to rupture (vulnerable plaques) might help to identify patients at risk for myocardial infarction or stroke. The most accepted features of plaque vulnerability include: thin cap fibroatheroma, large lipid core, intimal spotty calcification, positive remodeling and intraplaque neovascularizations. Today, research is focusing on finding imaging techniques that are less invasive, less radiation and can detect most of the vulnerable plaque features. While, carotid atherosclerosis can be visualized using noninvasive imaging, such as US, MRI and CT, imaging plaque feature in coronary arteries needs invasive imaging modalities. However, atherosclerosis is a systemic disease with plaque development simultaneously in different arteries and data acquisition in carotid arteries can add useful information for prediction of coronary events.

  • 10.
    Jashari, Fisnik
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Bajraktari, Gani
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Coronary and carotid atherosclerosis: similarities and differences2013In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 227, no 2, p. 193-200Article in journal (Refereed)
    Abstract [en]

    Although a relationship is commonly accepted between coronary and carotid arterial disease, suggesting that atherosclerosis is a systemic condition, the extent of this association and correspondence has not been fully elucidated. This review discusses recent research in this field and highlights areas for future study. The prevalence of severe carotid stenosis increases with prevalence of coronary stenosis, with the latter being found in a significant number of stroke patients, while those with carotid stenosis may be at higher risk of myocardial infarction than stroke. There also appear to be common risk factors (age, diabetes, hypertension, smoking and dyslipidemia), although the effects in both vascular systems may not be identical. Furthermore, while the degree of stenosis in the coronary artery has little ability to predict acute coronary syndrome, which is caused by local thrombosis from a ruptured or eroded plaque, severe carotid stenosis causing hypoperfusion is highly predictive of stroke, although this effect may be time-limited. This apparent difference in event mechanism in the two arteries is interesting as is the difference in the rate of development of collaterals. Overall, the evidence shows that a clear relationship exists between disease in the coronary and carotid arteries, since conventional risk factors and the extent of stenosis and/or previous events emanating from one artery have a strong bearing on the prevalence of events in the other artery. Nevertheless, the exact correspondence between the two arteries is unclear, with sometimes contradictory study results. More research is needed to identify the full extent of risk factors for severe stenosis and cardio- or cerebral vascular events, among which, inflammatory biomarkers such as hs-CRP and prior vascular events are likely to play a key role.

  • 11.
    Koulaouzidis, George
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Charisopoulou, Dafni
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    McArthur, T
    Jenkins, PJ
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Coronary artery calcification is not related to coronary heart disease isolated family history2013Article in journal (Other academic)
  • 12.
    Koulaouzidis, George
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Charisopoulou, Dafni
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Jenkins, P. J. J.
    Mcarthur, T.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Comparison of coronary heart disease in South Asian angina pantients and caucasians with the use of CT angiography2013In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 12, no Supplement: 1, p. S71-S72, Meeting Abstract: P192Article in journal (Other academic)
  • 13.
    Koulaouzidis, George
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Charisopoulou, Dafni
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    McArthur, T
    Jenkins, PJ
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Aggressive and diffuse coronary calcification in South Asian angina patients compared to Caucasians with similar risk factors2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 167, no 6, p. 2472-2476Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Ethnic differences in prevalence and severity of coronary artery disease are well established and are usually attributed to risk factors variation. This study investigates the differences in coronary artery narrowing and coronary calcification between two age- and gender-matched cohorts of South Asian and Caucasian symptomatic angina patients.

    METHODS: We identified 101 symptomatic angina patients of South Asian origin who had undergone CT angiography and calcium scoring, and compared them with 101 age and gender matched Caucasian patients.

    RESULTS: South Asians had a greater mean number of arterial segments with both obstructive and non-obstructive plaque than Caucasians (p=0.006 and p=0.0003, respectively) and higher prevalence of triple-vessel disease (p=0.0004). Similarly, South Asians had a higher mean CAC score (p<0.0001) and the percentage of South Asians with CAC>0 and in all categories of CAC score 100-1000 were also higher, as was the number of arterial segments with calcified and non-calcified plaque. These results were more marked in patients aged >50 but in those ≤50, Caucasians showed a higher mean number of diseased segments (p=0.019), with non-obstructive plaque (p=0.02), possibly suggesting that Caucasians are likely to have more diffuse atherosclerosis at an earlier age. CAC prevalence and severity in this age-group were not significantly different between South Asians and Caucasians.

    CONCLUSION: Despite similar conventional risk factors for CAD, symptomatic South Asians seem to have more aggressive and diffuse arterial calcification compared to Caucasians. These differences are more profound above the age of 50, suggesting potential genetic or other risk factors yet to be determined.

  • 14.
    Koulaouzidis, George
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    MacArthur, T.
    Jenkins, P. J.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Coronary artery calcification correlates with the presence and severity of valve calcification2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 168, no 6, p. 5263-5266Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate the prevalence of coronary artery calcification (CAC) in symptomatic individuals with CT evidence for left heart valve calcification, aortic valve (AVC), mitral valve (MAC) or both.

    METHODS: This is a retrospective study of 282 consecutive patients with calcification in either the aortic valve or mitral annulus. Calcium scoring of the coronary artery, aortic and mitral valve was measured using the Agatston score.

    RESULTS: AVC was more prevalent than MAC (64% vs. 2.5%, p<0.001), with 34% having both. Absence of CAC was noted in 12.7% of the study population. AVC+CAC were observed in 53.5%, MAC and CAC in 2.1%, and combined AVC, MAC and CAC in 31.6%. The median CAC score was higher in individuals with combined AVC+MAC, followed by those with AVC and lowest was in the MAC group. The majority (40%) of individuals with AVC had CAC score >400, and only in 16% had CAC=0. The same pattern was more evident in individuals with AVC+MAC, where 70% had CAC score >400 and only 6% had CAC score of 0. These results were irrespective of gender. There was no correlation between AVC and MAC but there was modest correlation between CAC score and AVC score (r=0.28, p=0.0001), MAC (r=0.36, p=0.0001) and with combined AVC+MAC (r=0.5, p=0.0001). AVC score of 262 had a sensitivity of 78% and specificity of 92% for the prediction of presence of CAC.

    CONCLUSION: The presence and extent of calcification in the aortic valve or/and mitral valves are associated with severe coronary artery calcification.

  • 15.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Heart centre, Umeå university.
    Correlation between coronary and valve calcification: review of current evidence2013In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 1, p. 19-24Article, review/survey (Refereed)
    Abstract [en]

    We carried out a review of the correlation between calcification of different arteries and valves and their risk factors to determine the extent of the association. We found a strong correlation between calcification presence, extent and progression between different arterial beds and the aortic valve, suggesting that calcification is a systemic diffuse disease, affecting the arterial tree as a whole. Despite this strong association, a comparison between coronary artery calcification (CAC) and calcification of other arteries may not be strictly valid, since only intimal calcification is seen in the coronary artery while other arteries may also contain medial calcification, with current scanning modalities being incapable of detecting the difference. Furthermore the pathogenesis of each type may be different.

    Calcification seems to appear first in the coronary artery in younger adults but may be more prevalent in the aorta in the elderly, although the incidence is notably higher in the abdominal aorta among women. Mitral annulus calcification (MAC) occurs less frequently than aortic valve calcification (AVC) in asymptomatic subjects only. MAC is correlated with calcification of the aorta and advanced MAC is found with higher CAC but there is little relationship with AVC and calcification of other arterial beds. As with the coronary artery, in the aorta and aortic valve, calcium begets calcium. Although age, male gender and possibly systolic hypertension are most frequently associated with arterial calcification, there is little consistency for other conventional risk factors and MAC and abdominal aortic calcification may be more prevalent among postmenopausal women. When the presence of CAC is factored in as a risk factor for calcification of the other arteries, multivariate analysis shows no additional significant risk factors except age.

    Although AVC has been viewed as a cardiac manifestation of atherosclerosis, we found little evidence to suggest that this is also true of MAC.

  • 16.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Environmental contaminants and congenital heart defects: a re-evaluation of the evidence2018In: International Journal of Environmental Research and Public Health, ISSN 1661-7827, E-ISSN 1660-4601, Vol. 15, no 10, article id 2096Article, review/survey (Refereed)
    Abstract [en]

    Congenital heart defects (CHDs) are a common birth defect of largely unknown etiology, with high fetal and neonatal mortality. A review of CHDs and environmental contaminant exposure found that meta-analyses showed only modest associations for smoking, vehicle exhaust components, disinfectant by-products and proximity to incinerators, with stronger results from the newer, larger and better quality studies masked by the typical absence of effect in older studies. Recent studies of exposure to agricultural pesticides, solvents, metals and landfill sites also showed associations. Certain contaminants have been associated with certain CHDs, with septal defects being the most common. Frequent methodological problems include failure to account for potential confounders or maternal/paternal preconception exposure, differences in diagnosing, defining and classifying CHDs, grouping of defects to increase power, grouping of contaminants with dissimilar mechanisms, exclusion of pregnancies that result in death or later life diagnosis, and the assumption that maternal residence at birth is the same as at conception. Furthermore, most studies use measurement estimates of one exposure, ignoring the many additional contaminant exposures in daily life. All these problems can distort and underestimate the true associations. Impaired methylation is a common mechanism, suggesting that supplementary folate may be protective for any birth defect.

  • 17.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Insights into the relationship between coronary calcification and atherosclerosis risk factors2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction

    Coronary artery disease (CAD) is the most common cause of death in Europe and North America and early detection of atherosclerosis is a clinical priority. Diagnosis of CAD remains conventional angiography, although recent technology has introduced non-invasive imaging of coronary arteries using computed tomographic coronary angiography (CTCA), which enables the detection and quantification of coronary artery calcification (CAC). CAC forms within the arterial wall and is usually found in or adjacent to atherosclerotic plaques and is consequently known as sub-clinical atherosclerosis.

     The conventional cardiovascular (CV) risk factors used to quantify the estimated 10-year coronary event risk comprise dyslipidaemia, hypertension, diabetes mellitus, obesity, smoking and family history of CAD. Nevertheless, their relationship with significant (>50%) stenosis, their interaction with the CAC score and their predictive ability for CAC presence and extent has not been fully determined in symptomatic patients.

     

    Methods 

     For Papers 1-4 we took patients from the Euro-CCAD cohort, an international study established in 2009 in Umeå, Sweden. The study data gave us the CAC score and the CV risk factor profile in 6309 patients, together with angiography results for a reduced cohort of 5515 patients. In Papers 1 and 2 we assessed the risk factors for significant stenosis, including CAC as a risk factor. Paper 2 carried out this analysis by geographical region: Europe vs USA and northern vs southern Europe. Paper 3 investigated the CV risk factors for CAC presence, stratified by age and gender, while Paper 4 assessed the CV risk factors for CAC extent, stratified by gender.

     In paper 5 we carried out a systematic review and meta-analysis of all studies of the risk factor predictors of CAC presence, extent and progression in symptomatic patients. From a total of 884 studies, we identified 10 which fitted our inclusion criteria, providing us with a total of 15,769 symptomatic patients. All 10 were entered in the systematic review and 7 were also eligible for the meta-analysis.

     

    Results

    Paper 1:           Among risk factors alone, the most powerful predictors of significant coronary stenosis were male gender followed by diabetes, smoking, hypercholesterolaemia, hypertension, family history of CAD and age; only obesity was not predictive. When including the log transformed CAC score as a risk factor, this proved the most powerful predictor of >50% stenosis, but hypercholesterolaemia and hypertension lost their predictive ability. The conventional risk factors alone were 70% accurate in predicting significant stenosis, the log transformed CAC score alone was 82% accurate but the combination was 84% accurate and improved both sensitivity and specificity.

     Paper 2:           Despite some striking differences in profiles between Europe and the USA, the most important risk factors for >50% stenosis in both groups were male gender followed by diabetes. When the log CAC score was included as a risk factor, it became by far the most important predictor of >50% stenosis in both continents, followed by male gender. In the northern vs southern Europe comparison the result was similar, with the log CAC score being the most important predictor of >50% stenosis in both regions, followed by male gender.

     Paper 3:           Independent predictors of CAC presence in males and females were age, dyslipidaemia, hypertension, diabetes and smoking, with the addition of family history of CAD in males; obesity was not predictive in either gender. The most important predictors of CAC presence in males were dyslipidaemia and diabetes, while among females the most important predictors of CAC presence were diabetes followed by smoking. When analysed by age groups, in both males and females aged <70 years, diabetes, hypertension and dyslipidaemia were predictive, with diabetes being the strongest; in females aged <70 years, smoking was also predictive. Among those aged ≥70 years, the results are completely different, with only dyslipidaemia being predictive in males but smoking and diabetes were predictive in females.

     Paper 4:           In the total cohort, age, male gender, diabetes, obesity, family history of CAD and number of risk factors predicted an increasing CAC score, with the most important being male gender and diabetes. In males, hypertension and dyslipidaemia were also predictive, although diabetes was the most important predictor. Diabetes was similarly the most important risk factor in females, followed by age and number of risk factors. Among patients with CAC, hypertension, dyslipidaemia and diabetes predicted CAC extent in both males and females, with diabetes being the strongest predictor in males followed by dyslipidaemia, while diabetes was also the strongest predictor in females, followed by hypertension. Quantile regression confirmed the consistent predictive ability of diabetes.

     Paper 5:           In the systematic review, age was strongly predictive of both CAC presence and extent but not of CAC progression. The results for CAC presence were overwhelmed by data from one study of almost 10,000 patients, which found that white ethnicity, diabetes, hypertension and obesity were predictive of CAC presence but not male gender, dyslipidaemia, family history or smoking. With respect to CAC extent, only male gender and hypertension were clearly predictive, while in the one study of CAC progression, only diabetes and hypertension were predictive. In the meta-analysis, hypertension followed by male gender, diabetes and age were predictive of CAC presence, while for CAC extent mild-moderate CAC was predicted by hypertension alone, whereas severe CAC was predicted by hypertension followed by diabetes.

     

    Conclusion

    Our investigation of the Euro-CCAD cohort showed that the CAC score is far more predictive of significant stenosis than risk factors alone, followed by male gender and diabetes, and there was little benefit to risk factor assessment over and above the CAC score for >50% stenosis prediction. Regional variations made little difference to this result. Independent predictors of CAC presence were dyslipidaemia and diabetes in males and diabetes followed by smoking in females. The risk factor predictors alter at age 70. The most important risk factor predictors of CAC extent were male gender and diabetes; when analysed by gender, diabetes was the most important in both males and females. Our studies have consistently shown the strong predictive ability of male gender in the total cohort and diabetes in males and females and this is reflected in the meta-analysis, which also found hypertension to be independently predictive. Interestingly, dyslipidaemia does not appear to be a strong risk factor.

     

  • 18.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Arterial calcification: A new perspective?2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 228, p. 11-22Article, review/survey (Refereed)
    Abstract [en]

    Arterial calcification is commonly seen in atherosclerosis, chronic kidney disease (CKD) and diabetes and has long been considered a natural progression of atherosclerosis. Yet it is a systemic condition, occurring in a wide and diverse range of disease states and no medical treatment for cardiovascular disease has yet found a way to regress it; on the contrary, lipid-lowering therapy may worsen its progression. Although numerous studies have found associations between calcification and biomarkers, none has yet found a unifying mechanism that explains the calcification found in atherosclerosis, CKD or diabetes and many of the biomarkers are equally associated with atheroma development and cardiovascular events. Furthermore, both presence and absence of coronary artery calcification appear predictive of plaque rupture and cardiovascular events, indicating that the association is not causal. This suggests that we are no further forward in understanding the true nature of arterial calcification or its pathogenesis, other than noting that it is 'multifactorial'. This is because most researchers view arterial calcification as a progressive pathological condition which must be treated. Instead, we hypothesise that calcification develops as an immune response to endothelial injury, such as shear stress or oxidative stress in diabetics, and is consequently part of the body's natural defences. This would explain why it has been found to be protective of plaque rupture and why it is unresponsive to lipid-lowering agents. We propose that instead of attempting to treat arterial calcification, we should instead be attempting to prevent or treat all causes of endothelial injury.

  • 19.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Extensive coronary calcification: a clinically unrecognised condition2010In: Current Vascular Pharmacology, ISSN 1570-1611, E-ISSN 1875-6212, Vol. 8, no 5, p. 701-705Article in journal (Refereed)
    Abstract [en]

    Atheroma calcification is a common feature of advanced atherosclerosis, however with the advent of CT scanning it has become possible to detect extensive coronary calcification in the absence of flow-limiting lesions. While this phenomenon is known in renal disease, it also exists in some patients with exertional angina. Vascular pathology suggests biomineralisation associated with development of osteoblast-like cells in the arterial wall. While some conventional risk factors are shared with atheroma formation, others such as ethnicity and medications appear more specific to extensive calcification and may mirror those for osteoporosis. Similarly an atherogenic diet can predispose to both conditions while some elements promote or inhibit coronary calcification but not atheroma formation. The immune and endocrine systems contribute to both conditions but not necessarily in the same way, with vitamins D and K more related to calcification than atheroma formation. Finally, statins significantly lower low density lipoprotein (LDL) cholesterol and reduce atheroma formation but are largely powerless against extensive calcification. Although investigations into the exact cause of extensive coronary calcification are in their infancy, early results suggest that it is sufficiently different in nature from atheroma formation to be considered as a separate condition. Further research would yield a greater understanding, which would aid management and the development of specific biomarkers to reduce the cost and radiation risk of CT scanning.

  • 20.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Canterbury Christ Church University, Kent , UK.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Canterbury Christ Church University, Kent , UK.
    South Asians and their increased cardiovascular risk: A review of risk factors and diet and lifestyle modification2013In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 2, p. 74-78Article, review/survey (Refereed)
    Abstract [en]

    South Asians (SAs) have a significantly higher incidence and severity of type 2 diabetes and cardiovascular disease (CVD) than Caucasians and can present with atypical ischaemic symptoms. This can present a challenge for health professionals who may not be aware of the lowered thresholds recommended for SA body mass index, waist circumference and age. Although SAs are likely to have all the hallmarks of metabolic syndrome: central obesity, insulin resistance, impaired glucose tolerance, reduced high density lipoprotein, high triglycerides and hypertension, conventional risk factors alone do not fully predict the increased CVD risk among this community. Furthermore, SAs themselves may not be aware of their increased predisposition to disease nor of the dietary and lifestyle modifications which could reduce the risk and severity of their condition. Even where some modification has been attempted, there may be cultural pressure to conform to a traditional diet and the requirements for fasting and feasting. Principally, SAs should avoid large late meals, reduce sugary sweets and drinks, alcohol and foods fried in plant oils which create damaging transfats, while increasing protein and non-fried vegetables to help glycaemic control. Chewing paan, with or without added tobacco, is a particular risk factor for both CVD and cancer, on a par with the dangers of smoking. Although not in the culture, exercise would also be of great benefit.

  • 21.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Air pollution and its cardiovascular and other risks2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 271, no 5, p. 429-432Article in journal (Refereed)
  • 22.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Alcohol and the heart2011In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 35, no 10, p. 1737-1738Article in journal (Refereed)
    Abstract [en]

    Alcohol consumption and disease or mortality display a J-shaped curve, with moderate amounts of alcohol being more protective than abstention, binge drinking, or heavy drinking. Red wine appears to be particularly protective for cardiovascular disease and associated conditions such as type 2 diabetes. There are, however, controversies concerning the effect of red wine on hypertension, in which there may be significant gender and ethnic differences. Overall, it seems that both ethanol and the polyphenols in red wine may contribute to the protective effect.

  • 23.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Umeå Heart Centre.
    Arterial calcification: Friend or foe?2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 167, no 2, p. 322-327Article in journal (Refereed)
    Abstract [en]

    There is a significant relationship between the presence, extent and progression of coronary artery calcification (CAC) and cardiovascular (CV) events and mortality in both CV and renal patients and CAC scoring can provide improved predictive ability over risk factor scoring alone. There is also a close relationship between CAC presence and atherosclerotic plaque burden, with angiography studies showing very high sensitivity but poor specificity of CAC score for predicting obstructive disease. Nevertheless, there are objections to CAC screening because of uncertainties and lack of studies showing improved outcome. Furthermore, histopathology studies indicate that heavily calcified plaque is unlikely to result in a CV event, while the vulnerable plaque tends to be uncalcified or 'mixed', suggesting that calcification may be protective. This scenario highlights a number of paradoxes, which may indicate that the association between CAC and CV events is spurious, following from the adoption of CAC as a surrogate for high plaque burden, which itself is a surrogate for the presence of vulnerable plaque. Since studies indicate that arterial calcification is a complex, organised and regulated process similar to bone formation, there is no particular reason why it should be a reliable indicator of either the plaque burden or the risk of a future CV event. We suggest that it is time to divorce arterial calcification from atherosclerosis and to view it as a distinct pathology in its own right, albeit one which frequently coexists with atherosclerosis and is related to it for reasons which are not yet fully understood.

  • 24.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Calcific cardiac disease: a comprehensive investigation into its true nature2010In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 145, no 3, p. 599-600Article in journal (Refereed)
  • 25.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Caloric Restriction and Its Effect on Blood Pressure, Heart Rate Variability and Arterial Stiffness and Dilatation: A Review of the Evidence2018In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, no 3, article id 751Article, review/survey (Refereed)
    Abstract [en]

    Essential hypertension, fast heart rate, low heart rate variability, sympathetic nervous system dominance over parasympathetic, arterial stiffness, endothelial dysfunction and poor flow-mediated arterial dilatation are all associated with cardiovascular mortality and morbidity. This review of randomised controlled trials and other studies demonstrates that caloric restriction (CR) is capable of significantly improving all these parameters, normalising blood pressure (BP) and allowing patients to discontinue antihypertensive medication, while never becoming hypotensive. CR appears to be effective regardless of age, gender, ethnicity, weight, body mass index (BMI) or a diagnosis of metabolic syndrome or type 2 diabetes, but the greatest benefit is usually observed in the sickest subjects and BP may continue to improve during the refeeding period. Exercise enhances the effects of CR only in hypertensive subjects. There is as yet no consensus on the mechanism of effect of CR and it may be multifactorial. Several studies have suggested that improvement in BP is related to improvement in insulin sensitivity, as well as increased nitric oxide production through improved endothelial function. In addition, CR is known to induce SIRT1, a nutrient sensor, which is linked to a number of beneficial effects in the body.

  • 26.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hypertension and lifestyle modification: how useful are the guidelines?2010In: British Journal of General Practice, ISSN 0960-1643, E-ISSN 1478-5242, Vol. 60, no 581, p. 879-880Article in journal (Refereed)
  • 27.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Personalised Medicine: Moving Away from Large Randomised Controlled Trials?2013In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 1, p. 2-2Article in journal (Refereed)
  • 28.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. Canterbury Christ Church University, Kent , UK.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The predictive value of arterial and valvular calcification for mortality and cardiovascular events2014In: IJC Heart & Vessels, ISSN 2214-7632, Vol. 3, p. 1-5Article, review/survey (Refereed)
    Abstract [en]

    A review of the predictive ability of arterial and valvular calcification has shown an additive effect of calcification in more than 1 location in predicting mortality and coronary heart disease, with mitral annual calcification being a particularly strong predictor. In individual arteries and valves there is a clear association between calcification presence, extent and progression and future cardiovascular events and mortality in asymptomatic, symptomatic and high risk patients, although adjustment for calcification in other arterial beds generally renders associations non-significant. Furthermore, in acute coronary syndrome, culprit plaque is normally not calcified. This would tend to reduce the validity of calcification as a predictor and suggest that the association with cardiovascular events and mortality may not be causal. The association with stroke is less clear; carotid and intracranial artery calcification show little predictive ability, with symptomatic plaques tending to be uncalcified.

  • 29.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Howard, John McLaren
    Acumen, Tiverton EX16 0AJ, Devon, England.
    The acid-ash hypothesis revisited: a reassessment of the impact of dietary acidity on bone2014In: Journal of Bone and Mineral Metabolism, ISSN 0914-8779, E-ISSN 1435-5604, Vol. 32, no 5, p. 469-475Article, review/survey (Refereed)
    Abstract [en]

    The acid-ash hypothesis states that when there are excess blood protons, bone is eroded to provide alkali to buffer the net acidity and maintain physiologic pH. There is concern that with the typical Western diet, we are permanently in a state of net endogenous acid production, which is gradually reducing bone. While it is clear that a high acid-producing diet generates increased urinary acid and calcium excretion, the effect of diet does not always have the expected results on BMD, fracture risk and markers of bone formation and resorption, suggesting that other factors are influencing the effect of acid/alkali loading on bone. High dietary protein, sodium and phosphorus intake, all of which are necessary for bone formation, were thought to be net acid forming and contribute to low BMD and fracture risk, but appear under certain conditions to be beneficial, with the effect of protein being driven by calcium repletion. Dietary salt can increase short-term markers of bone resorption but may also trigger 1,25(OH)2D synthesis to increase calcium absorption; with low calcium intake, salt intake may be inversely correlated with BMD but with high calcium intake, salt intake was positively correlated with BMD. With respect to the effect of phosphorus, the data are conflicting. Inclusion of an analysis of calcium intake may help to reconcile the contradictory results seen in many of the studies of bone. The acid-ash hypothesis could, therefore, be amended to state that with an acid-producing diet and low calcium intake, bone is eroded to provide alkali to buffer excess protons but where calcium intake is high the acid-producing diet may be protective.

  • 30.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Howard, John McLaren
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    A Review of the Effect of Diet on Cardiovascular Calcification2015In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 16, no 4, p. 8861-8883Article, review/survey (Refereed)
    Abstract [en]

    Cardiovascular (CV) calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum management for these patients. For this reason, a review of studies investigating diet and serum levels of macro- and micronutrients was carried out. Although there were few human studies of macronutrients, nevertheless transfats and simple sugars should be avoided, while long chain -3 fats from oily fish may be protective. Among the micronutrients, an intake of 800 g/day calcium was beneficial in those without renal disease or hyperparathyroidism, while inorganic phosphorus from food preservatives and colas may induce calcification. A high intake of magnesium (380 mg/day) and phylloquinone (500 g/day) proved protective, as did a serum 25(OH)D concentration of 75 nmol/L. Although oxidative damage appears to be a cause of CV calcification, the antioxidant vitamins proved to be largely ineffective, while supplementation of -tocopherol may induce calcification. Nevertheless other antioxidant compounds (epigallocatechin gallate from green tea and resveratrol from red wine) were protective. Finally, a homocysteine concentration >12 mu mol/L was predictive of CV calcification, although a plasma folate concentration of >39.4 nmol/L could both lower homocysteine and protect against calcification. In terms of a dietary programme, these recommendations indicate avoiding sugar and the transfats and preservatives found in processed foods and drinks and adopting a diet high in oily fish and vegetables. The micronutrients magnesium and vitamin K may be worthy of further investigation as a treatment option for CV calcification.

  • 31.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    McLaren Howard, John
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Cardiovascular and Renal Calcification and Bone: A comparison of the effect of Dietary Fatty Acids2014In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 3, p. 127-131Article, review/survey (Refereed)
    Abstract [en]

    Cardiovascular (CV) and renal calcification is regularly found with osteoporosis and both are conditions of chronic inflammation and oxidative stress. Intake of dietary fatty acids is known to impact on the incidence of CV disease and bone loss but few studies have specifically looked at their impact on CV or renal calcification. This review found that although a very high total fat intake is likely to prove detrimental to both tissues and bone, particularly with low calcium intake, human studies often show mixed results, possibly because fatty acid intake shows a U-shaped dose/response curve, contrary to the expected linear relationship. Nevertheless, intake of fish and fish oil are generally found to protect against ectopic calcification and bone loss, with a low omega 6 to omega 3 ratio (preferably <5:1) proving critical. Fish intake of 3-4 servings a week was believed to be optimal. In arteries, the relationship between fish oil intake and other markers of sub-clinical atherosclerosis, such as intima-medial thickness, may be stronger than their relationship with arterial calcification. Any association with arterial calcification often lost significance after adjustment for CV risk factors, suggesting that fish oil may act principally by lowering risk factors and calling into question whether CV calcification is a condition of dyslipidaemia.

  • 32.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    McLaren Howard, John
    Acumen Lab, Tiverton, Devon, UK.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Cardiovascular calcification and bone: a comparison of the effects of dietary and serum antioxidants2015In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 2, no 1, p. 8-15Article, review/survey (Refereed)
    Abstract [en]

    Severe cardiovascular (CV) calcification can manifest as fully formed bone and is regularly found with osteoporosis; both have been shown to be associated with oxidative stress. Studies of the effect of antioxidants on CV calcification are few, but show that deficiency can induce both CV calcification and bone loss, while in conditions of oxidative stress such as renal failure, diabetes and smoking or in osteoporosis and fracture, antioxidants can reduce CV calcification and improve bone. The benefit of antioxidants in healthy adults is less clear and some may be detrimental. Higher intake of α-tocopherol (105.5mg/d vs 76.4mg/d) and β-cryptoxanthin may increase risk of CV calcification while high intake of retinol (≥3000mcg/d) may increase hip fracture risk, although possibly only with vitamin D intake ≤440IU/d; the carotenoids lycopene and β-carotene, however, appear beneficial in bone. Vitamin C shows little effect on CV calcification, although longer term supplementation may improve bone mineral density where calcium intake is >500mg/d. Potential reasons for this include a U-shaped dose/response curve for the fat-soluble antioxidants vitamins A and E (with peak bone mass achieved with retinol intake of 600–840 mcg/d), a failure to measure baseline concentrations so that the response cannot be stratified by requirement, the need to be replete in calcium and vitamin D and supplementation of the wrong isomer of vitamin E. Finally, although little studied, tocotrienols, tocopherols (with the exception of α-tocopherol), resveratrol, epigallocatechin gallate, quercetin, α-lipoic acid and N-acetylcysteine may be effective in both the CV system and bone.

  • 33.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    McLaren Howard, John
    Acumen Lab, Tiverton, Devon, UK.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Cardiovascular Calcification and Bone: A Comparison of The Effects of Dietary and Serum Calcium, Phosphorous, Magnesium and Vitamin D2014In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 5, p. 209-218Article, review/survey (Refereed)
    Abstract [en]

    This comparison of the effects of calcium, phosphorus, magnesium and vitamin D on cardiovascular (CV) calcification and bone has shown that in general the micronutrients that promote bone health also protect the arteries. We have shown that adequate amounts of all three minerals should be ingested, paying particular attention to supplementing calcium to bind high phosphorus and to ensure the maximum benefit from supplementing vitamin D. It appears that the optimum intake for bone is >800 mg/d calcium, with postmenopausal women possibly requiring a total intake of 1100mg/d. Both CV and bone studies suggest achieving a serum 25(OH)D level of >75nmol/l. These relationships are valid for a Caucasian population, however,and may not hold in African Americans and Asians. The recent concerns that calcium supplementation may increase CV disease risk has largely proved groundless, with higher calcium intake improving dyslipidaemia, hypertension and mortality. With respect to higher serum phosphate, there is an association with CV calcification and CVD risk even within the normal range, suggesting that the reference ranges may need to be redefined for 'at risk' patients. CV calcification was reduced in CKD patients with magnesium intake in the range 384-669mg/d. When considering the complex interplay of the action of the minerals together with their regulators vitamin D, PTH and FGF23, it is clear that this is a very sophisticated system which attempts to maintain calcium homeostasis to the possible detriment of bone and arteries. This reinforces the need to ensure adequate calcium intake before supplementing vitamin D.

  • 34.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    McLaren Howard, John
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Cardiovascular Calcification and Bone: A Comparison of the Effects of Dietary and Serum Vitamin K and its Dependent Proteins2015In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 4, p. 7-13Article, review/survey (Refereed)
    Abstract [en]

    This review compares the effect of vitamin K on cardiovascular (CV) calcification and bone health and shows that, in principal, the γ-carboxylation of the vitamin K-dependent proteins matrix Gla protein (MGP) and its bone equivalent osteocalcin (OC), generally ensures that hydroxyapatite is kept out of the CV system and is deposited in bone. This is an important finding, since there is currently no reliable treatment for CV calcification.Vitamin K2 (menaquinone) may be more effective in the arteries, while vitamin K1 (phylloquinone) is more active in bone. Nevertheless, there remains considerable uncertainty over the precise scope of the functions of MGP and OC, and their carboxylated and under-carboxylated forms, as well as the newly discovered vitamin K-dependent proteins. Although a diet high in vegetables could deliver adequate phylloquinone, supplementation of menaquinone may be necessary for those at risk of CV calcification. Several animal studies and one human study have demonstrated that arterial calcification could be reduced with vitamin K supplementation and there are further trials in progress. Patients on warfarin are particularly prone to CV calcification but there has been concern that supplementation would either counter warfarin treatment or destabilise INR. In fact, studies suggest that low dose phylloquinone did not increase coagulation and may improve the stability of anticoagulant therapy. Furthermore, use of oral anticoagulants which do not affect vitamin K metabolism, such as ximelagatran, could be used when there is a need for vitamin K supplementation for artery or bone health.

  • 35.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    McLaren Howard, John
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Ectopic calcification and bone: a comparison of the effect of dietary carbohydrates, sugars and protein2014In: International Cardiovascular Forum Journal, ISSN 2410-2636, Vol. 1, no 4, p. 175-179Article in journal (Refereed)
    Abstract [en]

    A number of studies have shown that severe calcification of the arteries, heart and kidneys commonly coexists withosteoporosis, particularly in renal disease. We have already shown that with respect to dietary fats, those that promoteectopic (mainly cardiovascular) calcification are also detrimental to bone, with a similar relationship seen in fats which inhibitectopic calcification. This review of dietary carbohydrates, sugars and protein has shown a similar correspondence of effect,with protein proving protective against ectopic calcification, at least in animals, and beneficial to bone. There appears to bean interaction with calcium intake, with the beneficial effects of high protein being negated in a calcium deficiency, while ahigh calcium intake enhances the dangers of a low protein intake; the cut-off for calcium intake may be around 800mg/dfor bone health. The results of studies on carbohydrates are unclear. Although there are no human studies on ectopiccalcification and intake of sugars, diabetes mellitus, insulin resistance and high blood glucose are known risk factors and arealso detrimental to bone. Fructose consistently promotes ectopic calcification in animals and is detrimental to bone in bothanimals and humans, although the results for sucrose, glucose and lactose are mixed. Protein and prebiotics, both protectiveagainst ectopic calcification and beneficial to bone, appear to act by increasing calcium absorption. Mechanisms of actionshared between inhibition of ectopic calcification and increased bone mineral density (BMD) include insulin-like growth factor(IGF)-1, which can be directly induced by protein and glucose, and advanced glycation end products (AGEs), which decreaseexpression of IGF-1 and generate reactive oxygen species, promote ectopic calcification and increased bone resorption.

  • 36.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Mickley, H.
    Overhus, K.
    Diederichsen, A.
    Gueret, P.
    Cademartini, F.
    Schmermund, A.
    Zamorano, P.
    Budoff, M.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The impact of risk factors on predicting significant stenosis in the presence and absence of coronary calcification: results from the Euro-CCAD study2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, p. 761-762Article in journal (Other academic)
  • 37.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Overhus, K.
    Diederichsen, A. C. P.
    Gueret, P.
    Cademartiri, F.
    Maffi, E.
    Schmermund, A.
    Zamorano, P.
    Budoff, M.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Euro-CCAD: differing conventional atherosclerosis risk factors for coronary calcification depending on degree of luminal stenosis2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no Supplement 1, Meeting abstract P6452, p. 1157-1157Article in journal (Other academic)
  • 38.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Schmermund, A.
    Cardiology, Bethanian Hospital, Frankfurt, Germany.
    Diederichsen, A.
    Cardiology, Odense University Hospital, Odense, Denmark.
    Mickley, H.
    Cardiology, Odense University Hospital, Odense, Denmark.
    Overhus, K.
    Cardiology, Odense University Hospital, Odense, Denmark.
    Zamorano, P.
    Cardiology, University Hospital Ramón y Cajal Carretera, Madrid, Spain.
    Gueret, P.
    Cardiology, Hôpital Henri Mondor Creteil, France.
    Maffi, E.
    Cardiology, Giovanni XXIII Hospital, Italy.
    Cademartiri, F.
    Cardiology, Giovanni XXIII Hospital, Italy.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Euro-ccad: Differing conventional atherosclerosis risk factors for coronary calcification depending on degree of luminal stenosis2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E81-E82Article in journal (Other academic)
  • 39.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Ctr Heart, Umea, Sweden.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zhao, Y.
    Diederichsen, A.
    Mickley, H.
    Ovrehus, K.
    Zamorano, P.
    Gueret, P.
    Schmermund, A.
    Maffei, E.
    Cademartiri, F.
    Budoff, M.
    Henein, M.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients: Euro-CCAD study2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 207, p. 13-19Article in journal (Refereed)
    Abstract [en]

    Aims: In this retrospective study we assessed the predictive value of the coronary calcium score for significant (>50%) stenosis relative to conventional risk factors. Methods and Results: We investigated 5515 symptomatic patients from Denmark, France, Germany, Italy, Spain and the USA. All had risk factor assessment, computed tomographic coronary angiogram (CTCA) or conventional angiography and a CT scan for coronary artery calcium (CAC) scoring. 1539 (27.9%) patients had significant stenosis, 5.50 of whom had zero CAC. In 5074 patients, multiple binary regression showed the most important predictor of significant stenosis to be male gender (B = 1.07) followed by diabetes mellitus (B = 0.70) smoking, hypercholesterolaemia, hypertension, family history of CAD and age but not obesity. When the log transformed CAC score was included, it became the most powerful predictor (B = 1.25), followed by male gender (B = 0.48), diabetes, smoking, family history and age but hypercholesterolaemia and hypertension lost significance. The CAC score is a more accurate predictor of >50% stenosis than risk factors regardless of the means of assessment of stenosis. The sensitivity of risk factors, CAC score and the combination for prediction of >50% stenosis when measured by conventional angiogram was considerably higher than when assessed by CTCA but the specificity was considerably higher when assessed by CTCA. The accuracy of CTCA for predicting >50% stenosis using the CAC score alone was higher (AUC 0.85) than using a combination of the CAC score and risk factors with conventional angiography (AUC 0.81). Conclusion: In symptomatic patients, the CAC score is a more accurate predictor of significant coronary stenosis than conventional risk factors.

  • 40.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wiklund, Urban
    Zhao, Y.
    Diederichsen, A.
    Mickley, H.
    Ovrehus, K.
    Zamorano, P.
    Gueret, P.
    Schmermund, A.
    Maffei, E.
    Cademartiri, F.
    Budoff, M.
    Henein, Michael
    Diabetes and male gender are key risk factor predictors of CAC extent: a Euro-CCAD study2016Manuscript (preprint) (Other academic)
    Abstract [en]

    Background and aims: Although much has been written about the risk factor predictors of CAC extent, few studies have been carried out on symptomatic patients. Similarly, no study has directly compared predictors of CAC extent and zero CAC.

    Methods: From the European Calcific Coronary Artery Disease (Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and USA. All had risk factor assessment and CT scanning for CAC scoring.

     Results: Among all patients, male gender (β = 1.36, p<0.001) and diabetes (β = 0.47, p<0.001) were the most important risk factors of CAC extent, with age, diabetes (DM), obesity, family history of CAD and number of risk factors also being predictive. Among patients with CAC, DM, hypertension (HT) and dyslipidaemia (DL) were predictors of an increasing CAC score in males and females, with DM being the strongest (p<0.001 for both). These results were echoed in quantile regression, where DM was consistently the most important predictor of CAC extent in every quantile in both males and females. HT and DL were also predictive but to a lesser extent, with HT being predictive in the high CAC quantiles and DL in the low CAC quantiles.

     Conclusion: In addition to male gender, DM is the most important predictor of CAC extent in both genders.  

  • 41.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zhao, Ying
    Diederichsen, A.
    Mickley, H.
    Ovrehus, K.
    Zamorano, J.
    Gueret, P.
    Schmermund, A.
    Maffei, E.
    Cademartiri, F.
    Budoff, M.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Gender and age effects on risk factor-based prediction of coronary artery calcium in symptomatic patients: a Euro-CCAD study2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 252, p. 32-39Article in journal (Refereed)
    Abstract [en]

    Background and aims: The influence of gender and age on risk factor prediction of coronary artery calcification (CAC) presence in symptomatic patients is unclear.

    Methods: From the European Calcific Coronary Artery Disease (EURO-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and USA. All had risk factor assessment and CT scanning for CAC scoring.

     Results: The prevalence of CAC among females was lower than among males in all age groups. Using multivariate logistic regression, age, dyslipidaemia, hypertension, diabetes and smoking were independently predictive of CAC presence in both genders. In addition to a progressive increase in CAC with age, the most important predictors of CAC presence were dyslipidaemia and diabetes (β = 0.64 and 0.63 respectively) in males and diabetes (β = 1.08) followed by smoking (β = 0.68) in females; these same risk factors were also important in predicting increasing CAC scores. There was no difference in the predictive ability of diabetes, hypertension and dyslipidaemia in either gender for CAC presence in patients aged <50 and 50-70 years. However, in patients aged >70, only dyslipidaemia predicted CAC presence in males and only smoking and diabetes were predictive in females. 

     

    Conclusion:  In symptomatic patients, there are significant differences in the ability of conventional risk factors to predict CAC presence between genders and between patients aged <70 and ≥70, indicating the important role of age in predicting CAC presence.

  • 42.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Zhao, Ying
    Ibrahimi, Pranvera
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Diabetes and Hypertension Consistently Predict the Presence and Extent of Coronary Artery Calcification in Symptomatic Patients: A Systematic Review and Meta-Analysis2016In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 17, no 9, article id 1481Article, review/survey (Refereed)
    Abstract [en]

    Background: The relationship of conventional cardiovascular risk factors (age, gender, ethnicity, diabetes, dyslipidaemia, hypertension, obesity, exercise, and the number of risk factors) to coronary artery calcification (CAC) presence and extent has never before been assessed in a systematic review and meta-analysis.

    Methods: We included only English language studies that assessed at least three conventional risk factors apart from age, gender, and ethnicity, but excluded studies in which all patients had another confirmed condition such as renal disease.

    Results: In total, 10 studies, comprising 15,769 patients, were investigated in the systematic review and seven studies, comprising 12,682 patients, were included in the meta-analysis, which demonstrated the importance of diabetes and hypertension as predictors of CAC presence and extent, with age also predicting CAC presence. Male gender, dyslipidaemia, family history of coronary artery disease, obesity, and smoking were overall not predictive of either CAC presence or extent, despite dyslipidaemia being a key risk factor for coronary artery disease (CAD).

    Conclusion: Diabetes and hypertension consistently predict the presence and extent of CAC in symptomatic patients.

     

  • 43.
    Nicoll, Rachel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Zhao, Ying
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Diederichsen, Axel
    Mickley, Hans
    Ovrehus, Kristian
    Zamorano, Jose
    Gueret, Pascal
    Schmermund, Axel
    Maffei, Erica
    Cademartiri, Filippo
    Budoff, Matt
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Diabetes and male sex are key risk factor correlates of the extent of coronary artery calcification: a Euro-CCAD study2017In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 31, no 7, p. 1096-1102Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Although much has been written about the conventional cardiovascular risk factor correlates of the extent of coronary artery calcification (CAC), few studies have been carried out on symptomatic patients. This paper assesses the potential ability of risk factors to associate with an increasing CAC score. Methods: From the European Calcific Coronary Artery Disease (Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and the USA. All had conventional cardiovascular risk factor assessment and CI scanning for CAC scoring. Results: Among all patients, male sex (OR = 4.85, p < 0.001) and diabetes (OR = 236, p < 0.001) were the most important risk factors of CAC extent, with age, hypertension, dyslipidemia and smoking also showing a relationship. Among patients with CAC, age, diabetes, hypertension and dyslipidemia were associated with an increasing CAC score in males and females, with diabetes being the strongest dichotomous risk factor (p < 0.001 for both). These results were echoed in quantile regression, where diabetes was consistently the most important correlate with CAC extent in every quantile in both males and females. To a lesser extent, hypertension and dyslipidemia were also associated in the high CAC quantiles and the low CAC quantiles respectively. Conclusion: In addition to age and male sex in the total population, diabetes is the most important correlate of CAC extent in both sexes.

  • 44. Zhao, Y.
    et al.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Diederichsen, A.
    Mickley, H.
    Ovrehus, K.
    Zamorano, P.
    Gueret, P.
    Schmermund, A.
    Maffei, E.
    Cademartiri, F.
    Budoff, M.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Coronary calcification and male gender predict significant stenosis in symptomatic patients in northern and southern Europe and the USA: A Euro-CCAD study2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645Article in journal (Refereed)
    Abstract [en]

    Background: Significant stenosis is the principal cause of stable angina but its predictors and their variation by geographical region are unclear.

    Methods and Results: From the European Calcific Coronary Artery Disease (Euro-CCAD) cohort, we retrospectively investigated 5515 symptomatic patients from northern Europe (Denmark, France, Germany), southern Europe (Italy, Spain) and USA. All had conventional cardiovascular risk factor assessment, angiography and CT scanning for coronary artery calcium (CAC) scoring. There were considerable differences in the patient characteristics between the groups, with the USA patients being younger and having more diet and lifestyle-related risk factors, although hypertension may have been better controlled than in Europe. USA patients had a two-fold increase in prevalence of significant stenosis and a three-fold increase in median CAC score. In all three groups, the log CAC score proved to be the strongest predictor of >50% stenosis followed by male gender. In the USA group there were no additional independently predictive risk factors, although in northern Europe obesity, hypertension, smoking and hypercholesterolaemia remained predictive, with all risk factors other than age and hypertension proving to be predictive in the southern Europe group. Without the CAC score as a variable, male gender followed by diabetes were the most important predictors in all three regions, with hypertension also proving predictive in northern Europe.

     Conclusion:  In symptomatic patients, the CAC score and male gender were the most important predictors of significant stenosis in symptomatic patients in northern and southern Europe and the USA.

  • 45. Zhao, Ying
    et al.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    He, Yi Hua
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The effect of statins on valve function and calcification in aortic stenosis: A meta-analysis2016In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 246, p. 318-324Article in journal (Refereed)
    Abstract [en]

    Background: Aortic calcification has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. In view of the existing conflicting results, we aimed to provide objective evidence on the effect of statins in aortic stenosis (AS).

    Methods and results: A meta-analysis of eligible studies that used statins in AS was performed. Fourteen studies were identified, 5 randomized controlled trials (RCTs) and 9 observational studies. In the 14 studies as a whole, no significant differences were found in all cause mortality (OR = 0.98, p = 0.91), cardiovascular mortality (OR = 0.80, P = 0.23) or the need for valve replacement (OR = 0.93, p = 0.45) between the statins and the control groups. LDL-cholesterol dropped in the statins groups in both <24 months and ≥24 months follow-up (p < 0.001 for both) but not in controls (p = 0.35 and p = 0.33, respectively). In the <24 months statins group, the annual increase in peak aortic velocity and peak gradient was less (p < 0.0001 and p = 0.004, respectively), but the mean gradient, valve area and calcification score were not different from controls. In the ≥24 months statins group, none of the above parameters was different from controls.

    Conclusions: Despite the consistent beneficial effect of statins on LDL-cholesterol levels, the available evidence showed no effect on aortic valve structure, function or calcification and no benefit for clinical outcomes.

  • 46. Zhao, Ying
    et al.
    Nicoll, Rachel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    He, Yi Hua
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    The effect of statins therapy in aortic stenosis: Meta-analysis comparison data of RCTs and observationals.2016In: Data in brief, ISSN 2352-3409, Vol. 7, p. 357-361Article in journal (Refereed)
    Abstract [en]

    Aortic stenosis has been shown to share the same risk factors as atherosclerosis which suggested a potential benefit from statins therapy. Fourteen studies which provided the effect of statins treatment on aortic stenosis (AS) were meta-analyzed, including 5 randomized controlled trials (RCTs) and 9 observational studies. In the RCTs, statins did not have any influence on peak aortic valve velocity, peak valve gradient, mean valve gradient, aortic valve area and aortic calcification compared to controls. In the observational studies, the peak valve velocity, peak gradient and aortic valve area showed less progression in the statins group compared to controls. This article describes data related article title "The effect of statins on valve function and calcification in aortic stenosis: a meta-analysis" (Zhao et al., 2016) [1].

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