| 1. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 2. |
- Chau, Kénora, et al.
(författare)
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Obesity and metabolic features associated with long-term developing diastolic dysfunction in an initially healthy population-based cohort
- 2018
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Ingår i: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 107:10, s. 887-896
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diastolic dysfunction (DD) is increasingly common. However, its metabolic determinants are poorly known. This study aims to determine which metabolic and inflammatory features predict DD in initially healthy adults. Methods: We prospectively analyzed the association between metabolic features and DD in 728 initially healthy adults aged 30–60 from Eastern France enrolled in the STANISLAS population-based cohort. Clinical and biological cardiovascular features were collected at baseline (1994–1995). DD was assessed twenty years later (2011–2016) by echocardiography using current international guidelines. For replication purposes, 1463 subjects from the Malmö Preventive Project cohort were analyzed. Results: In the STANISLAS cohort, 191 subjects (26.2%) developed DD. In age-sex-adjusted logistic models, significant predictors of DD were body mass index (BMI, odds ratio for 1-standard-deviation increase (OR) 1.28, 95% CI 1.08–1.52), waist circumference (WC, OR 1.48, 95% CI 1.18–1.84), waist-hip ratio (OR 1.53, 95% CI 1.16–2.02), systolic blood pressure (OR 1.19, 95% CI 1.00–1.43) and triglycerides (TG, OR 1.18, 95% CI 1.00–1.40). Subjects with elevated WC (> 80th percentile) and TG (> 50th percentile) had a twofold higher DD risk (age-sex-adjusted odds ratio 2.00, 95% CI 1.20–3.31, P = 0.008), whereas no such interplay was observed for BMI. In the Malmö cohort, BMI was similarly associated with DD; participants with both elevated BMI and TG were at higher DD risk (age-sex-adjusted odds ratio 1.61, 95% CI 1.18–2.20, P = 0.002). Conclusions: Subjects with elevated WC and TG may have a higher long-term DD risk. Prevention targeting visceral obesity may help reduce the incidence of DD.
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| 3. |
- Wood, Angela M., et al.
(författare)
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Risk thresholds for alcohol consumption : combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies
- 2018
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 391:10129, s. 1513-1523
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.Methods: We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12.5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5.6 years [5th-95th percentile 1.04-13.5]) from 71 011 participants from 37 studies.Findings: In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5.4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1.14, 95% CI, 1.10-1.17), coronary disease excluding myocardial infarction (1.06, 1.00-1.11), heart failure (1.09, 1.03-1.15), fatal hypertensive disease (1.24, 1.15-1.33); and fatal aortic aneurysm (1.15, 1.03-1.28). By contrast, increased alcohol consumption was loglinearly associated with a lower risk of myocardial infarction (HR 0.94, 0.91-0.97). In comparison to those who reported drinking >0-<= 100 g per week, those who reported drinking >100-<= 200 g per week, >200-<= 350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively.Interpretation: In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.
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| 4. |
- Després, Jean-Pierre, et al.
(författare)
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Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia.
- 2005
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Ingår i: The New England journal of medicine. - 1533-4406. ; 353:20, s. 2121-34
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been shown to reduce body weight and improve cardiovascular risk factors in obese patients. The Rimonabant in Obesity-Lipids (RIO-Lipids) study examined the effects of rimonabant on metabolic risk factors, including adiponectin levels, in high-risk patients who are overweight or obese and have dyslipidemia. METHODS: We randomly assigned 1036 overweight or obese patients (body-mass index [the weight in kilograms divided by the square of the height in meters], 27 to 40) with untreated dyslipidemia (triglyceride levels >1.69 to 7.90 mmol per liter, or a ratio of cholesterol to high-density lipoprotein [HDL] cholesterol of >4.5 among women and >5 among men) to double-blinded therapy with either placebo or rimonabant at a dose of 5 mg or 20 mg daily for 12 months in addition to a hypocaloric diet. RESULTS: The rates of completion of the study were 62.6 percent, 60.3 percent, and 63.9 percent in the placebo group, the group receiving 5 mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively. The most frequent adverse events resulting in discontinuation of the drug were depression, anxiety, and nausea. As compared with placebo, rimonabant at a dose of 20 mg was associated with a significant (P<0.001) mean weight loss (repeated-measures method, -6.7+/-0.5 kg, and last-observation-carried-forward analyses, -5.4+/-0.4 kg), reduction in waist circumference (repeated-measures method, -5.8+/-0.5 cm, and last-observation-carried-forward analyses, -4.7+/-0.5 cm), increase in HDL cholesterol (repeated-measures method, +10.0+/-1.6 percent, and last-observation-carried-forward analyses, +8.1+/-1.5 percent), and reduction in triglycerides (repeated-measures method, -13.0+/-3.5 percent, and last-observation-carried-forward analyses, -12.4+/-3.2 percent). Rimonabant at a dose of 20 mg also resulted in an increase in plasma adiponectin levels (repeated-measures method, 57.7 percent, and last-observation-carried-forward analyses, 46.2 percent; P<0.001), for a change that was partly independent of weight loss alone. CONCLUSIONS: Selective CB1-receptor blockade with rimonabant significantly reduces body weight and waist circumference and improves the profile of several metabolic risk factors in high-risk patients who are overweight or obese and have an atherogenic dyslipidemia.
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| 5. |
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| 6. |
- Tejani, Sanaa, et al.
(författare)
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Cardiometabolic Health Outcomes Associated With Discordant Visceral and Liver Fat Phenotypes: Insights From the Dallas Heart Study and UK Biobank
- 2022
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Ingår i: Mayo Clinic proceedings. - New York, United States : Elsevier. - 0025-6196 .- 1942-5546. ; 97:2, s. 225-237
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the cardiometabolic outcomes associated with discordant visceral adipose tissue (VAT) and liver fat (LF) phenotypes in 2 cohorts.Patients and Methods: Participants in the Dallas Heart Study underwent baseline imaging from January 1, 2000, through December 31, 2002, and were followed for incident cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) through 2013. Associations between VAT-LF groups (low-low, high-low, low-high, and high-high) and outcomes were assessed using multivariable- adjusted regression and were replicated in the independent UK Biobank.Results: The Dallas Heart Study included 2064 participants (mean SD age, 449 years; 54% female; 47% black). High VATehigh LF and high VATelow LF were associated with prevalent atheroscle- rosis, whereas low VATehigh LF was not. Of 1731 participants without CVD/T2DM, 128 (7.4%) developed CVD and 95 (5.5%) T2DM over a median of 12 years. High VATehigh LF and high VATelow LF were associated with increased risk of CVD (hazard ratios [HRs], 2.0 [95% CI, 1.3 to 3.2] and 2.4 [95% CI, 1.4 to 4.1], respectively) and T2DM (odds ratios [ORs], 7.8 [95% CI, 3.8 to 15.8] and 3.3 [95% CI, 1.4 to 7.8], respectively), whereas low VATehigh LF was associated with T2DM (OR, 2.7 [95% CI, 1.1 to 6.7]). In the UK Biobank (N1⁄422,354; April 2014-May 2020), only high VATelow LF remained associated with CVD after multivariable adjustment for age and body mass index (HR, 1.5 [95% CI, 1.2 to 1.9]).Conclusion: Although VAT and LF are each associated with cardiometabolic risk, these observations demonstrate the importance of separating their cardiometabolic implications when there is presence or absence of either or both in an individual.
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| 7. |
- Topol, Eric J, et al.
(författare)
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Rimonabant for prevention of cardiovascular events (CRESCENDO) : a randomised, multicentre, placebo-controlled trial.
- 2010
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 376:9740, s. 517-23
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Tidskriftsartikel (refereegranskat)abstract
- Background: Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant would improve major vascular event-free survival. Methods: This double-blind, placebo-controlled trial was undertaken in 974 hospitals in 42 countries. 18 695 patients with previously manifest or increased risk of vascular disease were randomly assigned to receive either rimonabant 20 mg (n=9381) or matching placebo (n=9314). Randomisation was stratified by centre, implemented with an independent interactive voice response system, and all study personnel and participants were masked to group assignment. The primary endpoint was the composite of cardiovascular death, myocardial infarction, or stroke, as determined via central adjudication. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00263042. Findings: At a mean follow-up of 13.8, months (95% CI 13.6-14.0), the trial was prematurely discontinued because of concerns by health regulatory authorities in three countries about suicide in individuals receiving rimonabant. All randomised participants were analysed. At the close of the trial (Nov 6, 2008), the composite primary endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 364 (3.9%) patients assigned to rimonabant and 375 (4.0%) assigned to placebo (hazard ratio 0.97, 95% CI 0.84-1.12, p=0.68). With rimonabant, gastrointestinal (3038 [33%] vs 2084 [22%]), neuropsychiatric (3028 [32%] vs 1989 [21%]), and serious psychiatric side-effects (232 [2.5%] vs 120 [1.3%]) were significantly increased compared with placebo. Four patients in the rimonabant group and one in the placebo group committed suicide. Interpretation: The premature termination of this trial has important lessons for drug development. A drug that was being marketed for weight loss, but being tested for improving cardiovascular outcomes, induced a level of serious neuropsychiatric effects that was deemed unacceptable by regulatory authorities, and both the drug and the trial were abruptly terminated.
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