Update on the use of fibrates: focus on bezafibrate

Low-density lipoprotein-cholesterol (LDL-C) is a well established coronary heart disease (CHD) risk factor. However, the ability of this metabolic risk factor alone to identify individuals at rigk for future CHD events is limited. The raised triglycerides-low high-density lipoprotein-cholesterol (HDL-C) dyslipidaemia was shown to be an important cardiovascular risk factor independently of LDL-C levels. Fibric acid derivatives (fibrates) have been used in clinical practice for more than 2 decades as a class of agents known to decrease triglyceride levels while substantially increasing HDL-C levels. Through peroxisome proliferator-activated α-receptors, fibrates have a significant impact on the synthesis of several apolipoproteins and enzymes of lipoprotein metabolism as well as on the expression of several genes involved in fibrinolysis and inflammation. Data from recent primary and secondary prevention clinical trials demonstrate the efficacy of fibrate therapy in patients with the raised triglycerides-low HDL-C dyslipidaemia. This review summarizes current data regarding mechanism of action and the metbolic effects of fibrates, as well as results from major clinical trials on the efficacy of this mode of lipid lowering therapy. In addition, recent data from subgroup analyses of the Bezafibrate Infarction Prevention trial, demonstrating several important metabolic and long-term cardiovascular effects of bezafibrate therapy, are detailed

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<p>All models adjusted to age, educational level, HDL cholesterol, chronic kidney disease, type 2 diabetes and BIP study arm.</p><p>* Transformation of power of 4 was used for the attention cognitive domain to approximate normality. Hence, only p values are tabulated.</p><p>Linear Regression Model of association between low UA (bottom quintile vs. higher) and cognitive performance for various subgroups.</p

Calcium antagonists and mortality in patients with coronary artery disease: A Cohort study of 11,575 patients

AbstractObjectives. This study sought to establish the risk ratio for mortality associated with calcium antagonists in a large population of patients with chronic coronary artery disease.Background. Recent reports have suggested that the use of short-acting nifedipine may cause an increase in overall mortality in patients with coronary artery disease and that a similar effect may be produced by other calcium antagonists, in particular those of the dihydropyridine type.Methods. Mortality data were obtained for 11,575 patients screened for the Bezafibrate Infarction Prevention study (5,843 with and 5,732 without calcium antagonists) after a mean follow-up period of 3.2 years.Results. There were 495 deaths (8.5%) in the calcium antagonist group compared with 410 in the control group (7.2%). The age-adjusted risk ratio for mortality was 1.08 (95% confidence interval [CI] 0.95 to 1.24). After adjustment for the differences between the groups in age and gender and the prevalence of previous myocardial infarction, angina pectoris, hypertension, New York Heart Association functional class, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and current smoking, the adjusted risk ratio declined to 0.97 (95% CI 0.84 to 1.11). After further adjustment for concomintant medication, the risk ratio was estimated at 0.94 (95% CI 0.82 to 1.08).Conclusions. The current analysis does not support the claim that calcium antagonist therapy in patients with chronic coronary artery disease, whether myocardial infarction survivors or others, harbors an increased risk of mortality

Alcohol Intake and Risk of Coronary Heart Disease in Younger, Middle-Aged, and Older Adults

BACKGROUND: Light-to-moderate alcohol consumption is associated with a reduced risk of coronary heart disease (CHD). This protective effect of alcohol, however, may be confined to middle-aged or older individuals. CHD Incidence is low in men younger than 40 and in women younger than 50 years and for this reason, study cohorts rarely have the power to investigate effects of alcohol on CHD risk in younger adults. This study examined whether the beneficial effect of alcohol on CHD depends on age. METHODS AND RESULTS: A pooled analysis of eight prospective studies from North America and Europe including 192,067 women and 74,919 men free of cardiovascular diseases, diabetes, and cancers at baseline. Average daily alcohol intake was assessed at baseline using a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups: hazard ratios among moderately drinking men (5.0–29.9 g/day) aged 39–50, 50–59, and 60+ years were 0.58 (95% C.I. 0.36 to 0.93), 0.72 (95% C.I. 0.60–0.86), and 0.85 (95% C.I. 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference (IRD) between abstainers and moderate consumers in younger adults (IRD=45 per 100,000; 90% C.I. 8 to 84), than in middle-aged (IRD=64 per 100,000; 90% C.I. 24 to 102) and older adults (IRD=89 per 100,000; 90% C.I. 44 to 140). Similar results were observed in women. CONCLUSIONS: Alcohol is also associated with a decreased risk of CHD in younger adults; however, the absolute risk was small compared with middle-aged and older adults

Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis

The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (Cindex) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.)

Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies

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 & Results: Using individual-participant data on 360737 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 overpredicted 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 \u3e_40years 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. Conclusions: 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