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Carlberg, Bo
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Publications (10 of 76) Show all publications
Wallace, S. E., Regalado, E. S., Gong, L., Janda, A. L., Guo, D.-c., Russo, C. F., . . . Milewicz, D. M. (2019). MYLK pathogenic variants aortic disease presentation, pregnancy risk, and characterization of pathogenic missense variants. Genetics in Medicine, 21(1), 144-151
Open this publication in new window or tab >>MYLK pathogenic variants aortic disease presentation, pregnancy risk, and characterization of pathogenic missense variants
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2019 (English)In: Genetics in Medicine, ISSN 1098-3600, E-ISSN 1530-0366, Vol. 21, no 1, p. 144-151Article in journal (Refereed) Published
Abstract [en]

Purpose: Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLKmissense variants are pathogenic and information to guide aortic disease management are limited.

Methods: Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed.

Results: Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm repair or dissection); the majority of these events (87%) were aortic dissections. Aortic diameters were minimally enlarged at the time of dissection in many cases. Time-to-aortic-event curves showed that missense pathogenic variant (PV) carriers have earlier-onset aortic events than null PV carriers. An MYLK missense variant segregated with aortic disease over five generations but decreases MYLK kinase acitivity marginally. Functional Assays fail to identify all pathogenic variants in MYLK.

Conclusion: These data further define the aortic phenotype associated with MYLKpathogenic variants. Given minimal aortic enlargement before dissection, an alternative approach to guide the timing of aortic repair is proposed based on the probability of a dissection at a given age.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
Keywords
acute aortic dissection, hereditary thoracic aortic disease, MYLK, myosin light-chain kinase, thoracic aortic surgery
National Category
Genetics
Identifiers
urn:nbn:se:umu:diva-155775 (URN)10.1038/s41436-018-0038-0 (DOI)000455403400020 ()29925964 (PubMedID)
Funder
NIH (National Institute of Health), RO1 HL109942NIH (National Institute of Health), P01HL110869-01
Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-01-28Bibliographically approved
Hannuksela, M., Johansson, B. & Carlberg, B. (2018). Aortic stiffness in families with inherited non-syndromic thoracic aortic disease. Scandinavian Cardiovascular Journal, 52(6), 301-307
Open this publication in new window or tab >>Aortic stiffness in families with inherited non-syndromic thoracic aortic disease
2018 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 6, p. 301-307Article in journal (Refereed) Published
Abstract [en]

Background. In families with an inherited form of non-syndromic thoracic aortic disease (TAAD), aortic diameter alone is not a reliable marker for disease occurrence or progression. To identify other parameters of aortic function, we studied aortic stiffness in families with TAAD. We also compared diameter measurements obtained by transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI).

Methods. Seven families, including 116 individuals, with non-syndromic TAAD, were studied. The aortic diameter was measured by TTE and MRI. Aortic stiffness was assessed as local distensibility in the ascending aorta and as regional and global pulse wave velocity (PWV). Individuals with a dilated thoracic aorta (n = 21) were compared with those without aortic dilatation (n = 95).

Results. Ascending aortic diameter measured by TTE strongly correlated with the diameter measured by MRI (r2 = 0.93). The individuals with dilated aortas were older than those without dilatation (49 vs 37 years old). Ascending aortic diameter increased and distensibility decreased with increasing age; while, PWV increased with age and diameter. Some young subjects without aortic dilatation showed increased aortic stiffness. Individuals with a dilated thoracic aorta had significantly higher PWV and lower distensibility, measured by MRI than individuals without dilatation.

Conclusions. Diameters measured with TTE agree with those measured by MRI. Aortic stiffness might be a complementary marker for aortic disease and progression when used with aortic diameter, especially in young individuals.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
Thoracic aortic aneurysm, thoracic aortic dissection, aortic stiffness, aortic distensibility, pulse wave velocity
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-134022 (URN)10.1080/14017431.2018.1546895 (DOI)000461087500002 ()30606081 (PubMedID)2-s2.0-85059522267 (Scopus ID)
Note

Originally included in thesis in manuscript form.

Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2019-04-02Bibliographically approved
Brunström, M. & Carlberg, B. (2018). Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis. JAMA Internal Medicine, 178(1), 28-36
Open this publication in new window or tab >>Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis
2018 (English)In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 178, no 1, p. 28-36Article in journal (Refereed) Published
Abstract [en]

Importance: High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated.

Objective: To assess the association between BP lowering treatment and death and CVD at different BP levels.

Data sources: Previous systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017.

Study selection: Randomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included.

Data extraction and synthesis: Data were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines.

Main outcomes and measures: Prespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease.

Results: Seventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07).

Conclusions and relevance: Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-143058 (URN)10.1001/jamainternmed.2017.6015 (DOI)000419113300009 ()29131895 (PubMedID)
Available from: 2017-12-14 Created: 2017-12-14 Last updated: 2019-05-16Bibliographically approved
Brunstrom, M., Carlberg, B. & Lindholm, L. H. (2018). Perspective from Sweden on the global impact of the 2017 american college of cardiology/american heart association hypertension guidelines: a "sprint" beyond evidence in the United States. Circulation, 137(9), 886-888
Open this publication in new window or tab >>Perspective from Sweden on the global impact of the 2017 american college of cardiology/american heart association hypertension guidelines: a "sprint" beyond evidence in the United States
2018 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, no 9, p. 886-888Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2018
Keywords
antiyhypertensive agents, blood pressure, blood pressure determination, guideline, hypertension
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-145778 (URN)10.1161/CIRCULATIONAHA.118.033632 (DOI)000426206800002 ()29483169 (PubMedID)
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-06-09Bibliographically approved
Brunström, M. & Carlberg, B. (2018). Questionable Conclusions Regarding Blood Pressure End Points Reply [Letter to the editor]. JAMA Internal Medicine, 178(4), 575-576
Open this publication in new window or tab >>Questionable Conclusions Regarding Blood Pressure End Points Reply
2018 (English)In: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 178, no 4, p. 575-576Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
American Medical Association, 2018
National Category
General Practice
Identifiers
urn:nbn:se:umu:diva-147333 (URN)10.1001/jamainternmed.2018.0029 (DOI)000428884500027 ()29610886 (PubMedID)
Available from: 2018-05-17 Created: 2018-05-17 Last updated: 2019-05-16Bibliographically approved
Brunström, M. & Carlberg, B. (2018). Response to 'SPRINTin context: meta-analysis of trials with baseline normotension and lowlevels of previous cardiovascular disease' Reply [Letter to the editor]. Journal of Hypertension, 36(7), 1603-1604
Open this publication in new window or tab >>Response to 'SPRINTin context: meta-analysis of trials with baseline normotension and lowlevels of previous cardiovascular disease' Reply
2018 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 7, p. 1603-1604Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-150171 (URN)10.1097/HJH.0000000000001759 (DOI)000434304400026 ()29847453 (PubMedID)
Available from: 2018-07-18 Created: 2018-07-18 Last updated: 2019-05-16Bibliographically approved
Brunström, M. & Carlberg, B. (2018). SPRINT in context: meta-analysis of trials with baseline normotension and low levels of previous cardiovascular disease. Journal of Hypertension, 36(5), 979-986
Open this publication in new window or tab >>SPRINT in context: meta-analysis of trials with baseline normotension and low levels of previous cardiovascular disease
2018 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 5, p. 979-986Article, review/survey (Refereed) Published
Abstract [en]

Objective: To estimate the effect of antihypertensive treatment in trials with baseline normotension and low levels of previous cardiovascular disease. To test if the results from SPRINT are compatible with those from other trials, and test the impact of SPRINT results on overall effect estimates. Methods: Systematic review and meta-analysis of randomized controlled trials with at least 1000 patient-years of follow-up, comparing antihypertensive treatment versus placebo, or different blood pressure goals against each other. Trials with at least 50% previous cardiovascular disease were excluded. Results: Sixteen trials, including 66816 participants, were included in the meta-analyses. Mean baseline SBP was 138mmHg, and mean difference between treatment arms was 5.5mmHg. Antihypertensive treatment was associated with a neutral effect on all-cause mortality [relative risk 0.98, 95% confidence interval (CI) 0.92-1.05] and major cardiovascular events (0.97, 0.91-1.03). Results from SPRINT differed significantly from those of other trials (P=0.012 for all-cause mortality; P=0.016 for major cardiovascular events), but overall effect estimates were similar when SPRINT was excluded (1.01, 0.95-1.06 for all-cause mortality; 0.98, 0.93-1.03 for major cardiovascular events). Treatment was associated with reduced risk of secondary outcomes stroke (0.84, 0.71-1.00) and heart failure (0.88, 0.78-0.98), although heterogeneity was high in the stroke analysis (I-2=54%). Conclusion: SPRINT results are not representative for trials with baseline normotension and low levels of previous cardiovascular disease. Antihypertensive treatment does not protect against death or major cardiovascular events in this setting.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
Keywords
antihypertensive agents, cardiovascular diseases, hypertension, meta-analysis, review, systematic
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-147292 (URN)10.1097/HJH.0000000000001663 (DOI)000429441700002 ()29300245 (PubMedID)
Available from: 2018-05-25 Created: 2018-05-25 Last updated: 2019-05-16Bibliographically approved
Brunström, M. & Carlberg, B. (2018). Standardization according to blood pressure lowering in meta-analyses of antihypertensive trials: comparison of three methodological approaches. Journal of Hypertension, 36(1), 4-15
Open this publication in new window or tab >>Standardization according to blood pressure lowering in meta-analyses of antihypertensive trials: comparison of three methodological approaches
2018 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 1, p. 4-15Article, review/survey (Refereed) Published
Abstract [en]

OBJECTIVE: Assess how standardization of relative risks (RRs) and standard errors (SEs), according to blood pressure differences within trials, affects heterogeneity, overall effect estimates and study weights in meta-analyses of antihypertensive treatment.

METHOD: Data from a previous systematic review were used. Three sets of analyses were performed, using both random-effects and fixed-effects model for meta-analyses. First, we used raw data from the included trials. Second, we standardized RRs as if SBP was reduced by 10 mmHg in all trials. Third, we standardized both RRs and SEs.

RESULTS: When RRs were standardized according to blood pressure lowering, heterogeneity between trials increased (I = 36 vs. 93% for mortality). This conferred large differences in treatment effect estimates using random-effects and fixed-effects model (RR 0.79, 95% confidence interval 0.70-0.89, respectively, 0.97, 0.94-0.99). When SEs were standardized, confidence intervals for individual trials widened, resulting in lower power to detect heterogeneity across trials. Study weights were dissociated from number of events in trials (P < 0.0001, R = 0.99 before standardization vs. P = 0.063, R = 0.05 after standardization). This induced a secondary shift in weight from trials with lower baseline SBP to trials with higher baseline SBP, resulting in exaggerated overall effect estimates.

CONCLUSION: Standardization of RRs exaggerates differences between trials and makes meta-analyses highly sensitive to choice of statistical method. Standardization of SEs masks heterogeneity and results in biased effect estimates.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2018
Keywords
antihypertensive agents, blood pressure targets, cardiovascular diseases, hypertension, metaanalysis, standardization, systematic review
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-143060 (URN)10.1097/HJH.0000000000001574 (DOI)000429316200001 ()28990987 (PubMedID)2-s2.0-85036545986 (Scopus ID)
Available from: 2017-12-14 Created: 2017-12-14 Last updated: 2019-05-16Bibliographically approved
Brunström, M., Eliasson, M., Nilsson, P. M. & Carlberg, B. (2017). Blood pressure treatment levels and choice of antihypertensive agent in people with diabetes mellitus: an overview of systematic reviews. Journal of Hypertension, 35, 435-462
Open this publication in new window or tab >>Blood pressure treatment levels and choice of antihypertensive agent in people with diabetes mellitus: an overview of systematic reviews
2017 (English)In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 35, p. 435-462Article, review/survey (Refereed) Published
Abstract [en]

OBJECTIVE: Multiple systematic reviews address the effect of antihypertensive treatment in people with diabetes. Here, we summarize current systematic reviews concerning antihypertensive treatment effect at different blood pressure (BP) levels, and relative treatment effect of different antihypertensive agents.

METHODS: We searched MEDLINE, BIOSIS, DARE and CDSR during years 2005-2016. Eligibility criteria, number of trials and participants, outcomes analysed, statistical methods used for data synthesis, and principal results were extracted for each review. Review quality was assessed using the assessment of multiple systematic reviews tool.

RESULTS: We found four reviews concerning BP treatment level. These consistently showed that the effect of antihypertensive treatment on mortality, cardiovascular disease and coronary heart disease was attenuated at lower BP levels. If SBP was more than 140 mmHg, treatment reduced all-cause and cardiovascular mortality, cardiovascular disease, stroke, myocardial infarction and heart failure. If SBP was less than 140 mmHg, treatment increased the risk of cardiovascular death. We found eight reviews concerning choice of agent. We found no difference between angiotensin-converting enzyme inhibitors, angotensin receptor blockers, beta-blockers, calcium channel blockers and diuretics in preventing all-cause or cardiovascular mortality, combined cardiovascular disease, coronary heart disease and end-stage renal disease. Minor differences exist for stroke and heart failure. Data were limited on people with type 1 diabetes and very elderly patients with type 2 diabetes. None of the reviews concerning choice of agent included all relevant trials.

CONCLUSION: The available evidence supports treatment in people with type 2 diabetes and SBP more than 140 mmHg, using any of the major antihypertensive drug classes.

Keywords
Quality improvement, Stroke registries, Stroke risk factors, Time trends
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-128528 (URN)10.1097/HJH.0000000000001183 (DOI)000393822200004 ()27870655 (PubMedID)
Available from: 2016-12-06 Created: 2016-12-06 Last updated: 2018-06-09Bibliographically approved
Persson, S.-E., Boman, K., Wanhainen, A., Carlberg, B. & Arnerlöv, C. (2017). Decreasing prevalence of abdominal aortic aneurysm and changes in cardiovascular risk factors. Journal of Vascular Surgery, 65(3), 651-658
Open this publication in new window or tab >>Decreasing prevalence of abdominal aortic aneurysm and changes in cardiovascular risk factors
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2017 (English)In: Journal of Vascular Surgery, ISSN 0741-5214, E-ISSN 1097-6809, Vol. 65, no 3, p. 651-658Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: A significant reduction in the incidence of cardiovascular disease, including abdominal aortic aneurysm (AAA), has been observed in the past decades. In this study, a small but geographically well defined and carefully characterized population, previously screened for AAA and risk factors, was re-examined 11 years later. The aim was to study the reduction of AAA prevalence and associated factors.

METHODS: All men and women aged 65 to 75 years living in the Norsjö municipality in northern Sweden in January 2010 were invited to an ultrasound examination of the abdominal aorta, registration of body parameters and cardiovascular risk factors, and blood sampling. An AAA was defined as an infrarenal aortic diameter ≥30 mm. Results were compared with a corresponding investigation conducted in 1999 in the same region.

RESULTS: A total of 602 subjects were invited, of whom 540 (90%) accepted. In 2010, the AAA prevalence was 5.7% (95% confidence interval [CI], 2.8%-8.5%) among men compared with 16.9% (95% CI, 12.3%-21.6%) in 1999 (P < .001). The corresponding figure for women was 1.1% (95% CI, 0.0%-2.4%) vs 3.5% (95% CI, 1.2%-5.8%; P = .080). A low prevalence of smoking was observed in 2010 as well as in 1999, with only 13% and 10% current smokers, respectively (P = .16). Treatment for hypertension was significantly more common in 2010 (58% vs 44%; P < .001). Statins increased in the population (34% in 2010 vs 3% in 1999; P < .001), and the lipid profile in women had improved significantly between 1999 and 2010.

CONCLUSIONS: A highly significant reduction in AAA prevalence was observed during 11 years in Norsjö. Treatment for hypertension and with statins was more frequent, whereas smoking habits remained low. This indicates that smoking is not the only driver behind AAA occurrence and that lifestyle changes and treatment of cardiovascular risk factors may play an equally important role in the observed recent decline in AAA prevalence.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-128529 (URN)10.1016/j.jvs.2016.08.091 (DOI)000397987900034 ()27793513 (PubMedID)
Available from: 2016-12-06 Created: 2016-12-06 Last updated: 2018-06-09Bibliographically approved
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