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Background: Aortic valve calcification (AVC) is an underlying pathophysiological mechanism in aortic stenosis, which shares many risk factors with diabetes. However, the association between dysglycemia and early stages of AVC remains unclear. The aim was to examine the associations between stages of dysglycemia and signs of AVC among middle-aged individuals from the general population.

Methods: This was a cross-sectional study from the Swedish CArdioPulmonary bioImage Study (SCAPIS) randomly enrolling 30,154 middle-aged men and women from six study sites in Sweden between 2013 and 2018. Glycemic status was based on the World Health Organization criteria (fasting blood glucose and/or HbA1c) and questionnaire-based answers on previous diseases and categorized as normoglycemia, prediabetes, newly detected diabetes and known diabetes. AVC was assessed on cardiac computed tomography (CT) and defined as evident or not.

Results: Of 29,331 individuals with data on glycemic status and AVC available, mean age was 57.5 years and normoglycemia was present in 76%, prediabetes in 16%, newly detected diabetes in 3% and known diabetes in 5%. The prevalence of AVC increased progressively across glycemic categories, particularly in males (8%, 11%, 14% and 17%; P < 0.01) compared to females (5%, 6%, 8% and 9%; P < 0.01). There was an association with AVC already in the early stages of dysglycemia; prediabetes (OR 1.16, 95% CI 1.02–1.31), newly detected diabetes (1.34 [1.05–1.71]) and known diabetes (1.61 [1.34–1.93]) after adjusting for age, sex, smoking, study site, low density lipoprotein-cholesterol and hypertension.

Conclusions: In this large, contemporary, and randomly selected population of middle-aged individuals, prediabetes, newly detected diabetes and known diabetes were all associated with CT-detected AVC. Further studies are warranted to investigate if managing dysglycemia, even in its early stages, may help slow down AVC progression.

Key features: 

• The Northern Sweden Health and Disease Study (NSHDS) was initiated in the mid-1980s. The NSHDS is a population-based prospective longitudinal cohort comprising >140 000 participants in the two northernmost regions in Sweden, Norrbotten and Västerbotten, with >240 000 blood samples and 1.5 million person-years of follow-up.
• The NSHDS includes three sub-cohorts: the Västerbotten Intervention Programme (VIP), the expanded Northern Sweden Monitoring of Trends and Determinants of Cardiovascular Disease (MONICA) Study, and the Mammography Screening Project (MSP). The VIP is both a community-based cardiometabolic intervention programme encouraging healthy lifestyle (targeting individuals 40, 50, and 60 years of age), and a corresponding research cohort. The MONICA is an observational study focusing on cardiovascular disease and its associated risk factors, recruiting individuals aged 25–74 years. The MSP recruited women attending mammography during 1995–2006. The NSHDS median participation age is 50 years (53% women).
• Most participants contribute data on health, lifestyle, anthropometric measures, blood pressure, blood lipids, and glucose tolerance, along with research blood samples that are fractionated, frozen within an hour of collection, and stored at –80°C. Linkage to registries, clinical cohorts, and biological tissue archives facilitates studies of well-characterized participants (often combined with intervention studies).
• Collaborations are encouraged. Additional information can be found at: info.brs@umu.se; https://www.umu.se/en/biobank

Background: Dyslipidaemia in patients with diabetes contributes to the risk of atherosclerotic cardiovascular disease. We aimed to identify a dyslipidemic profile associated with both dysglycemia and subclinical coronary atherosclerosis.

Methods: Study participants (n = 5050) were classified in three groups: normoglycemia, pre-diabetes, and diabetes. A coronary artery calcium score (CACS) > 0 defined subclinical coronary atherosclerosis. Two independent methods were used to identify, among 225 lipid biomarkers, those that were associated with pre-diabetes and diabetes and were further tested for association by zero inflated Poisson regression with CACS and with CACS burden in study participants with CACS>0. Estimates were adjusted for cardiovascular risk factors with an interaction term for dispensed lipid lowering drugs.

Results: Thirty-two biomarkers associated with prediabetes and diabetes were further investigated for association with CACS. HDL diameter [multi-adjusted OR of 0.85 and 95 %CI (0.78–0.92)] as well as free cholesterol, phospholipids and total lipids in extra large HDL were inversely associated with CACS. There was a borderline significant interaction between small HDL and dispensed lipid lowering drugs on the presence of CACS, with and multi-adjusted OR of 0.53 and 95 %CI (0.36–0.77). None of the 32 glycemic profile-related lipid biomarkers associated with the relative increase of CACS in those with CACS>0. No consistent association was observed between non-HDL lipoproteins and CACS.

Conclusions: Changes in composition and relative concentration of HDL associated with both dysglycemia and subclinical coronary atherosclerosis. Treatment with lipid lowering drugs may contribute to reduce the risk associated with high circulating levels of small HDL.

Aims: Helicobacter pylori (H. pylori) and its cytotoxin-associated gene A (CagA) have been associated with myocardial infarction (MI), but existing data are conflicting possibly due to limitations in study designs and lack of data on important confounders. The aim of this study was to determine whether H. pylori or CagA seropositivity is associated with incident MI, including MI phenotypes, and to describe temporal trends.

Methods: We used the Northern Sweden Health and Disease study, a prospective biobank with data from residents enrolled in a population-based cohort from health examinations between 1986 and 2006. A total of 826 first time MI cases with available blood samples from their index health examination were identified up to 2006. Each case was 1:2 matched with controls by age, sex, sample date and geographical area. Blood samples were analysed using ELISA to determine seroprevalence of H. pylori and CagA, which were then used to study the association with incident MI.

Results: The median age at baseline was 50 years, and 71% of participants were male. Seroprevalence of H. pylori and CagA was 46.5% and 32.1% in cases, respectively, compared to 43.7% and 30.6% in controls. Overall, H. pylori prevalence decreased over the study period. After multivariable adjustments, no significant association was observed between H. pylori seropositivity and incident MI (odds ratio: 1.15, 95% CI 0.94–1.42) nor between CagA-positive H. pylori and incident MI.

Conclusion: In a Swedish population-based cohort, no significant association was observed between H. pylori or CagA seropositivity and incidence of MI.

Objectives: The adipocyte-derived hormone leptin has been associated with the pathogenesis of cardiovascular disease. The mechanisms underlying this association are unclear but may relate to effects on the vascular endothelium. Our aim was to explore the effects of leptin on endothelial vasomotor and fibrinolytic function in healthy volunteers and patients with coronary artery disease.

Design: The vascular effects of leptin were assessed infusing recombinant human leptin in healthy volunteers during measuring vasomotor response by venous occlusion plethysmography. Additionally, circulating levels of leptin were analysed in relation to endothelial dysfunction in patients with established coronary artery disease.

Results: In healthy male volunteers, intra-arterial infusion of recombinant human leptin (80, 800 and 8,000 ng/min; n = 10) did not affect basal forearm blood flow, plasma tissue plasminogen activator (tPA) or plasminogen activator inhibitor type 1 concentrations (all p > 0.05). However, during concomitant co-infusion with leptin (800 ng/min; n = 10), drug-induced vasodilatation was reduced (p = 0.001), and tPA activity increased (p = 0.002). In patients with coronary artery disease, those with the high plasma leptin levels had reduced drug-induced vasodilatation (p < 0.001), and increased net release of tPA antigen and activity (p < 0.001 and p = 0.03, respectively) compared to those with low levels. The study has been registered retrospectively at Clinical Trials with number NCT04374500.

Conclusion: Intrabrachial leptin infusion did not affect the basal vascular tone, whereas acute and chronic hyperleptinemia was associated with blunted vasoreactivity in healthy volunteers, and in patients with coronary artery disease.

Background: During the COVID-19 pandemic, Sweden implemented social distancing measures to reduce infection rates. However, the recommendation meant to protect individuals particularly at risk may have had negative consequences. The aim of this study was to investigate the impact of the COVID-19 pandemic on very old Swedish peoples' mental health and factors associated with a decline in mental health.

Methods: We conducted a cross-sectional study among previous participants of the SilverMONICA (MONItoring of Trends and Determinants of CArdiovascular disease) study. Of 394 eligible participants, 257 (65.2%) agreed to participate. Of these, 250 individuals reported mental health impact from COVID-19. Structured telephone interviews were carried out during the spring of 2021. Data were analysed using the χ² test, t-test, and binary logistic regression.

Results: Of 250 individuals (mean age: 85.5 ± 3.3 years, 54.0% women), 75 (30.0%) reported a negative impact on mental health, while 175 (70.0%) reported either a positive impact (n = 4) or no impact at all (n = 171). In the binary logistic regression model, factors associated with a decline in mental health included loneliness (odds ratio [95% confidence interval]) (3.87 [1.83-8.17]) and difficulty adhering to social distancing recommendations (5.10 [1.92-13.53]). High morale was associated with positive or no impact on mental health (0.37 [0.17-0.82]).

Conclusions: A high percentage of very old people reported a negative impact on mental health from the COVID-19 pandemic, primarily from loneliness and difficulty adhering to social distancing measures, while high morale seemed to be a protective factor.

To investigate whether coronary artery disease (CAD) burden is associated with plasma levels of the myocardial biomarkers Troponin I (TropI) and NT-proBNP in a large population-based sample using a cross-sectional design. Coronary computerized tomography (CT) angiography was performed in 25,859 subjects without a history of atherosclerotic disease from SCAPIS study (age 50–65, 52% women). TropI and NT-proBNP were measured in plasma. Segment involvement score (SIS) was the primary exposure and TropI the primary outcome. Both SIS and coronary artery calcium score, were associated with TropI levels following adjustment for age, sex and multiple confounders (p < 0.001), with similar relationships in men and women. Proximal segments from all three coronary arteries were related to TropI levels independently of one another. Adding TropI to traditional risk factors marginally increased discrimination of atherosclerosis as compared to risk factors alone (C-statistics + 0.0005, p = 0.014). SIS was related also to NT-proBNP levels, mainly in men, but with lower estimates than TropI. The burden of CAD was related to TropI levels in both men and women. All three major coronary arteries contributed to this relationship. Adding TropI to traditional risk factors resulted in only marginally improved discrimination of coronary atherosclerosis.

Background: People with HIV (PWH) have a high burden of coronary plaques; however, the comparison to people without known HIV (PwoH) needs clarification.

Objectives: The purpose of this study was to determine coronary plaque burden/phenotype in PWH vs PwoH.

Methods: Nonstatin using participants from 3 contemporary populations without known coronary plaques with coronary CT were compared: the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) studying PWH without cardiovascular symptoms at low-to-moderate risk (n = 755); the SCAPIS (Swedish Cardiopulmonary Bioimage Study) of asymptomatic community PwoH at low-to-intermediate cardiovascular risk (n = 23,558); and the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) of stable chest pain PwoH (n = 2,291). The coronary plaque prevalence on coronary CT was compared, and comparisons were stratified by 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and coronary artery calcium (CAC) presence.

Results: Compared to SCAPIS and PROMISE PwoH, REPRIEVE PWH were younger (50.8 ± 5.8 vs 57.3 ± 4.3 and 60.0 ± 8.0 years; P < 0.001) and had lower ASCVD risk (5.0% ± 3.2% vs 6.0% ± 5.3% and 13.5% ± 11.0%; P < 0.001). More PWH had plaque compared to the asymptomatic cohort (48.5% vs 40.3%; P < 0.001). When stratified by ASCVD risk, PWH had more plaque compared to SCAPIS and a similar prevalence of plaque compared to PROMISE. CAC = 0 was more prevalent in PWH (REPRIEVE 65.2%; SCAPIS 61.6%; PROMISE 49.6%); among CAC = 0, plaque was more prevalent in PWH compared to the PwoH cohorts (REPRIEVE 20.8%; SCAPIS 5.4%; PROMISE 12.3%, P < 0.001).

Conclusions: Asymptomatic PWH in REPRIEVE had more plaque than asymptomatic PwoH in SCAPIS but had similar prevalence to a higher-risk stable chest pain cohort in PROMISE. In PWH, CAC = 0 does not reliably exclude plaque.

Introduction: Risk stratification scores such as the European Systematic COronary Risk Evaluation (SCORE) are used to guide individuals on cardiovascular disease (CVD) prevention. Adding high-sensitivity troponin I (hsTnI) to such risk scores has the potential to improve accuracy of CVD prediction. We investigated how applying hsTnI in addition to SCORE may impact management, outcome, and cost-effectiveness.

Methods: Characteristics of 72,190 apparently healthy individuals from the Biomarker for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project were included into a discrete-event simulation comparing two strategies for assessing CVD risk. The standard strategy reflecting current practice employed SCORE (SCORE); the alternative strategy involved adding hsTnI information for further stratifying SCORE risk categories (S-SCORE). Individuals were followed over ten years from baseline examination to CVD event, death or end of follow-up. The model tracked the occurrence of events and calculated direct costs of screening, prevention, and treatment from a European health system perspective. Cost-effectiveness was expressed as incremental cost-effectiveness ratio (ICER) in € per quality-adjusted life year (QALYs) gained during 10 years of follow-up. Outputs were validated against observed rates, and results were tested in deterministic and probabilistic sensitivity analyses.

Results: S-SCORE yielded a change in management for 10.0% of individuals, and a reduction in CVD events (4.85% vs. 5.38%, p<0.001) and mortality (6.80% vs. 7.04%, p<0.001). S-SCORE led to 23 (95%CI: 20–26) additional event-free years and 7 (95%CI: 5–9) additional QALYs per 1,000 subjects screened, and resulted in a relative risk reduction for CVD of 9.9% (95%CI: 7.3–13.5%) with a number needed to screen to prevent one event of 183 (95%CI: 172 to 203). S-SCORE increased costs per subject by 187€ (95%CI: 177 € to 196 €), leading to an ICER of 27,440€/QALY gained. Sensitivity analysis was performed with eligibility for treatment being the most sensitive.

Conclusion: Adding a person’s hsTnI value to SCORE can impact clinical decision making and eventually improves QALYs and is cost-effective compared to CVD prevention strategies using SCORE alone. Stratifying SCORE risk classes for hsTnI would likely offer cost-effective alternatives, particularly when targeting higher risk groups.

Background and Aims: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population.

Methods: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (<2 and ≥2 mg/L).

Results: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of <2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration <2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024).

Conclusions: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.