| 21. |
- Schmidt, Amand F., et al.
(författare)
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PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:2, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- Background Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects of PCSK9 inhibitors on diabetes risk. Methods In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA 1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. Findings Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0.09 mmol/L, 95% CI 0.02 to 0.15), bodyweight (1.03 kg, 0.24 to 1.82), waist-to-hip ratio (0.006, 0.003 to 0.010), and an odds ratio for type diabetes of 1.29 (1.11 to 1.50). Based on the collected data, we did not identify associations with HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -0.09 to 0.30). Interpretation PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefi ts of PCSK9 inhibitor treatment, as was previously done for statins.
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| 22. |
- Schmidt, Amand F., et al.
(författare)
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Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9
- 2019
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Ingår i: BMC Cardiovascular Disorders. - : BMC. - 1471-2261 .- 1471-2261. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.
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| 23. |
- Taki, Hina, et al.
(författare)
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Left ventricular hypertrophy : an ECG-based study of prevalence and risk factors in a multiethnic population
- 2023
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Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Left ventricular hypertrophy (LVH) is frequently seen in association with arterial hypertension and indicates poor prognosis. This study aimed to determine the prevalence of LVH and associated factors in a multiethnic population from Mauritius.Methods: Population-based health surveys were performed in 2009 and 2015 and included in total 8961 individuals aged 35–75 years with recorded 12-lead ECG. LVH was defined according to three criteria: Sokolow-Lyon, Cornell voltage and Cornell product. Data were collected about health and lifestyle behaviour. Anthropometry and blood pressure were measured. Fasting levels of blood lipids and glucose were determined, oral glucose tolerance test was performed in people without glucose-lowering medications.Results: The age-standardised prevalence of LVH was 9% (n=875) according to any of the three ECG criteria. Individuals with LVH were older, more likely to have hypertension, diabetes, known cardiovascular disease (CVD) and elevated levels of cholesterol and creatinine. Further, they were more likely to be of African descent (Creole) and have lower educational level. In a multivariable model, Creole (OR (95% CI)) (1.56 (1.33 to 1.83)), low educational level (1.49 (1.28 to 1.75)), hypertension (3.01 (2.55 to 3.56)), known CVD (1.42 (1.11 to 1.83)) and elevated creatinine (1.08 (1.03 to 1.14)) remained associated with LVH. Individuals with non-treated or uncontrolled hypertension had a higher risk for LVH (3.09 (95% CI 2.57 to 3.71) and 4.07 (95% CI 3.29 to 5.05), respectively), than individuals with well controlled hypertension or normotension.Conclusion: LVH occurs more frequently in individuals with hypertension, as well as in individuals with African ancestry and/or low education level.
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| 24. |
- Veronesi, Giovanni, et al.
(författare)
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Combined effect of educational status and cardiovascular risk factors on the incidence of coronary heart disease and stroke in European cohorts : implications for prevention
- 2017
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 24:4, s. 437-445
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Tidskriftsartikel (refereegranskat)abstract
- Background: The combined effect of social status and risk factors on the absolute risk of cardiovascular disease has been insufficiently investigated, but results provide guidance on who could benefit most through prevention.Methods: We followed 77,918 cardiovascular disease-free individuals aged 35-74 years at baseline, from 38 cohorts covering Nordic and Baltic countries, the UK and Central Europe, for a median of 12 years. Using Fine-Gray models in a competing-risks framework we estimated the effect of the interaction of education with smoking, blood pressure and body weight on the cumulative risk of incident acute coronary heart disease and stroke.Results: Compared with more educated smokers, the less educated had an added increase in absolute risk of cardiovascular disease of 3.1% ( 95% confidence interval+0.1%, +6.2%) in men and of 1.5% ( = 1.9%, +5.0%) in women, consistent across smoking categories. Conversely, the interaction was negative for overweight: -2.6% ( 95% CI: -5.6%, +0.3%) and obese: -3.6% ( -7.6%, +0.4%) men, suggesting that the more educated would benefit more from the same reduction in body weight. A weaker interaction was observed for body weight in women, and for blood pressure in both genders. Less educated men and women with a cluster of two or more risk factors had an added cardiovascular disease risk of 3.6% ( +0.1%, +7.0%) and of 2.6% ( - 0.5%, +5.6%), respectively, compared with their more educated counterparts.Conclusions: Socially disadvantaged subjects have more to gain from lifestyle and blood pressure modification, hopefully reducing both their risk and also social inequality in disease.
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| 25. |
- Veronesi, Giovanni, et al.
(författare)
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Educational class inequalities in the incidence of coronary heart disease in Europe
- 2016
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 102:12, s. 958-965
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To estimate the burden of social inequalities in coronary heart disease (CHD) and to identify their major determinants in 15 European populations.Methods: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) study comprised 49 cohorts of middle-aged European adults free of CHD (110 928 individuals) recruited mostly in the mid-1980s and 1990s, with comparable assessment of baseline risk and follow-up procedures. We derived three educational classes accounting for birth cohorts and used regression-based inequality measures of absolute differences in CHD rates and HRs (ie, Relative Index of Inequality, RII) for the least versus the most educated individuals.Results: N=6522 first CHD events occurred during a median follow-up of 12 years. Educational class inequalities accounted for 343 and 170 additional CHD events per 100 000 person-years in the least educated men and women compared with the most educated, respectively. These figures corresponded to 48% and 71% of the average event rates in each gender group. Inequalities in CHD mortality were mainly driven by incidence in the Nordic countries, Scotland and Lithuania, and by 28-day case-fatality in the remaining central/South European populations. The pooled RIIs were 1.6 (95% CI 1.4 to 1.8) in men and 2.0 (1.7 to 2.4) in women, consistently across population. Risk factors accounted for a third of inequalities in CHD incidence; smoking was the major mediator in men, and High-Density-Lipoprotein (HDL) cholesterol in women.Conclusions: Social inequalities in CHD are still widespread in Europe. Since the major determinants of inequalities followed geographical and gender-specific patterns, European-level interventions should be tailored across different European regions.
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| 26. |
- Vishram, Julie K. K., et al.
(författare)
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Do other cardiovascular risk factors influence the impact of age on the association between blood pressure and mortality? : The MORGAM Project
- 2014
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Ingår i: Journal of Hypertension. - : Ovid Technologies. - 0263-6352 .- 1473-5598. ; 32:5, s. 1025-1033
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate age-related shifts in the relative importance of SBP and DBP as predictors of cardiovascular mortality and all-cause mortality and whether these relations are influenced by other cardiovascular risk factors. Methods: Using 42 cohorts from the MORGAM Project with baseline between 1982 and 1997, 85 772 apparently healthy Europeans and Australians aged 19-78 years were included. During 13.3 years of follow-up, 9.2% died (of whom 7.2% died due to stroke and 21.1% due to coronary heart disease, CHD). Results: Mortality risk was analyzed using hazard ratios per 10-mmHg/5-mmHg increase in SBP/DBP by multivariate-adjusted Cox regressions, including SBP and DBP simultaneously. Because of nonlinearity, SBP and DBP were analyzed separately for blood pressure (BP) values above and below a cut-point wherein mortality risk was the lowest. For the total population, significantly positive associations were found between stroke mortality and SBP [hazard ratio = 1.19 (1.13-1.25)] and DBP at least 78 mmHg [hazard ratio = 1.08 (1.02-1.14)], CHD mortality and SBP at least 116 mmHg [1.20 (1.16-1.24)], and all-cause mortality and SBP at least 120 mmHg [1.09 (1.08-1.11)] and DBP at least 82 mmHg [1.03 (1.02-1.05)]. BP values below the cut-points were inversely related to mortality risk. Taking into account the age x BP interaction, there was a gradual shift from DBP (19-26 years) to both DBP and SBP (27-62 years) and to SBP (63-78 years) as risk factors for stroke mortality and all-cause mortality, but not CHD mortality. The age at which the importance of SBP exceeded DBP was for stroke mortality influenced by sex, cholesterol, and country risk. Conclusion: Age-related shifts to the superiority of SBP exist for stroke mortality and all-cause mortality, and for stroke mortality was this shift influenced by other cardiovascular risk factors.
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| 27. |
- Vishram-Nielsen, Julie K. K., et al.
(författare)
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Does Estimated Pulse Wave Velocity Add Prognostic Information? : MORGAM Prospective Cohort Project
- 2020
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Ingår i: Hypertension. - : Lippincott Williams & Wilkins. - 0194-911X .- 1524-4563. ; 75:6, s. 1420-1428
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Tidskriftsartikel (refereegranskat)abstract
- The Reference Values for Arterial Stiffness Collaboration has derived an equation using age and mean blood pressure to estimated pulse wave velocity (ePWV), which predicted cardiovascular events independently of Systematic COoronary Risk Evaluation (SCORE) and Framingham Risk Score. The study aim was to investigate the independent association between ePWV and clinical outcomes in 107 599 apparently healthy subjects (53% men) aged 19 to 97 years from the MORGAM Project who were included between 1982 and 2002 in 38 cohorts from 11 countries. Using multiple Cox-regression analyses, the predictive value of ePWV was calculated adjusting for country of inclusion and either SCORE, Framingham Risk Score, or traditional cardiovascular risk factors (age, sex, smoking, systolic blood pressure, body mass index [BMI], total and high-density lipoprotein cholesterol). Cardiovascular mortality consisted of fatal stroke, fatal myocardial infarction, or coronary death, and the composite cardiovascular end point consisted of stroke, myocardial infarction, or coronary death. Model discrimination was assessed using Harrell's C-statistic. Adjusting for country and logSCORE or Framingham Risk Score, ePWV was associated with all-cause mortality (hazard ratio, 1.23 [95% CI 1.20-1.25] per m/s or 1.32 [1.29-1.34]), cardiovascular mortality (1.26 [1.21-1.32] or 1.35 [1.31-1.40]), and composite cardiovascular end point (1.19 [1.16-1.22] or 1.23 [1.20-1.25]; all P<0.001). However, after adjusting for traditional cardiovascular risk factors, ePWV was only associated with all-cause mortality (1.15 [1.08-1.22], P<0.001) and not with cardiovascular mortality (0.97 [0.91-1.03]) nor composite cardiovascular end point (1.10 [0.97-1.26]). The areas under the last 3 receiver operator characteristic curves remained unchanged when adding ePWV. Elevated ePWV was associated with subsequent mortality and cardiovascular morbidity independently of systematic coronary risk evaluation and Framingham Risk Score but not independently of traditional cardiovascular risk factors.
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| 28. |
- Vishram-Nielsen, Julie K.K., et al.
(författare)
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Predictive importance of blood pressure characteristics with increasing age in healthy men and women : The MORGAM Project
- 2021
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Ingår i: Hypertension. - : Lippincott Williams & Wilkins. - 0194-911X .- 1524-4563. ; 77:4, s. 1076-1085
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Tidskriftsartikel (refereegranskat)abstract
- It remains unclear which blood pressure (BP) characteristics best predict cardiovascular risk in different age groups and between sexes. We leveraged data from the MORGAM (MONICA [Monitoring of Trends and Determinants in Cardiovascular Disease], Risk, Genetics, Archiving and Monograph) Project to investigate determinants of BP characteristics and their prognostic importance, in younger and older (
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| 29. |
- Zhou, Bin, et al.
(författare)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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