European journal of preventive cardiology最新文献

Aims: Remnant cholesterol (RC) is the cholesterol content within triglyceride-rich lipoproteins. It promotes atherosclerotic cardiovascular disease beyond LDL cholesterol (LDL-C). The prognostic role of RC in patients with ST-segment elevation myocardial infarction (STEMI) is unknown. We aimed to estimate RC-related risk beyond LDL-C in patients with STEMI.

Methods and results: A total of 6602 consecutive patients with STEMI treated with primary percutaneous coronary intervention (PCI) from 1999 to 2016 were included. Remnant cholesterol was calculated as total cholesterol minus LDL-C minus HDL cholesterol. Adjusted Cox models were used to estimate the association between continuous RC levels and all-cause mortality, cardiovascular death, ischaemic stroke, and recurrent myocardial infarction (MI) at long-term (median follow-up of 6.0 years). Besides, discordance analyses were applied to examine the risk of the discordantly high RC (RC percentile rank minus LDL-C percentile rank > 10 units) compared with the discordantly low RC (LDL-C percentile rank minus RC percentile rank > 10 units). The concordance was defined as the percentile rank difference between RC and LDL-C ≤ 10 units. The median age of patients was 63 years [interquartile range (IQR) 54-72] and 74.8% were men. There were 2441, 1651, and 2510 patients in the discordantly low RC group, concordant group, and discordantly high RC group, respectively. All outcomes in the discordantly high RC group were higher than the other groups, and the event rate of all-cause mortality in this group was 31.87%. In the unadjusted analysis, the discordantly high RC was associated with increased all-cause mortality [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.63-2.04] and increased cardiovascular death (HR 1.79, 95% CI 1.55-2.06) compared with the discordantly low RC. In an adjusted model, RC was associated with higher all-cause mortality (HR 1.14, 95% CI 1.07-1.22). The discordantly high RC was associated with increased all-cause mortality (adjusted HR 1.55, 95% CI 1.37-1.75) and increased cardiovascular death (adjusted HR 1.47, 95% CI 1.25-1.72) compared with the discordantly low RC. There were no associations between RC and ischaemic stroke or recurrent MI.

Conclusion: In patients with STEMI treated with primary PCI, elevated RC levels beyond LDL-C and discordantly high RC were independently associated with increased all-cause mortality.

Aims: Remnant cholesterol and very low-density lipoprotein cholesterol (VLDL-C) are increasingly recognized risk factors for atherosclerotic disease with few therapeutic options. Angiopoietin-like 3 (ANGPTL3), a key protein in the metabolism of triglyceride-rich lipoproteins, is a promising target.

Methods and results: TRANSLATE-TIMI 70 was a double-blind, placebo-controlled randomized trial testing seven dose regimens of vupanorsen, an antisense oligonucleotide against ANGPTL3, in adults with non-HDL-C ≥ 100 mg/dL and triglycerides 150-500 mg/dL. The primary endpoint of this analysis was percentage change in remnant cholesterol (total cholesterol minus directly measured LDL-C minus HDL-C) and VLDL-C (directly measured) over 24 weeks. Two hundred eighty-six patients were enrolled, with a median age of 64 years and 44% female. Median baseline remnant cholesterol and VLDL-C were 42 and 31 mg/dL, respectively (reference: <30 mg/dL). Vupanorsen lowered remnant cholesterol by 42-59% at 24 weeks over placebo (P < 0.001), achieving a median level of 18 mg/dL at the highest dose. Over the same period, VLDL-C was reduced by 52-67% over placebo (P < 0.001), with a median achieved level of 2.5 mg/dL at the highest dose. The effect of vupanorsen on remnant cholesterol and VLDL-C reduction was dose-dependent and directly associated with the degree of ANGPTL3 inhibition: at 90% ANGPTL3 reduction, there was a 61% and 81% decrease in remnant cholesterol and VLDL-C, respectively.

Conclusion: Inhibition of ANGPTL3 protein synthesis significantly lowered remnant cholesterol and VLDL-C in patients with hypertriglyceridaemia. The magnitude of reduction was associated with the degree of ANGPTL3 inhibition. These findings support ANGPTL3 inhibition as a promising target for lowering cholesterol on triglyceride-rich lipoproteins.

Aims: The beneficial effects of exercise on reducing the risk of cardiovascular disease are established. However, the potential interaction between genetic risk for type 2 diabetes and physical activity on cardiovascular outcomes remains elusive. We aimed to investigate the effect of type 2 diabetes genetic risk-physical activity interaction on cardiovascular outcomes in individuals with diabetes.

Methods and results: Using the UK Biobank cohort, we investigated the effect of type 2 diabetes genetic risk-physical activity interaction on three-point and four-point major adverse cardiovascular events (MACE), in 25 701 diabetic participants. We used a polygenic risk score for type 2 diabetes (PRS_T2D) as a measure of genetic risk for type 2 diabetes. We observed a significant interaction between PRS_T2D and physical activity on cardiovascular outcomes (three-point MACE: P trend for interaction = 0.0081; four-point MACE: P trend for interaction = 0.0037). Among participants whose PRS_T2D was in the first or second quartile, but not in the third or fourth quartile, each 10 metabolic equivalents (METs) hours per week of physical activity decreased the risk of three-point or four-point MACE. Furthermore, restricted cubic spline analysis indicated that intense physical activity (>80 METs hours per week, which was self-reported by 12.7% of participants) increased the risk of cardiovascular outcomes among participants whose PRS_T2D was in the fourth quartile. Sub-group analysis suggested that negative impact of intense physical activity was observed only in non-insulin users.

Conclusion: The beneficial effect of physical activity on cardiovascular outcomes disappeared among those with high genetic risk for type 2 diabetes.

Aim: Blood pressure (BP) responses to exercise are frequently measured, with the concern that greater increases are a marker of disease. We sought to characterize the normal exercise BP response in healthy adults and its relationships with age, sex, and fitness.

Methods: 589 participants (median age 46 [IQR 24-56] years, 81% male) underwent cardiopulmonary exercise testing with repeated, automated BP measures. An exaggerated maximal systolic BP (SBPmax) was defined from current guidelines as ≥210 mmHg in males and ≥190 mmHg in females. Individual linear regression analyses defined the relationship between BP and workload (SBP/W-slope and DBP/W-slope). Participants with or without an exaggerated SBPmax and above or below median SBP/W-slope were compared.

Results: An exaggerated SBPmax was found in 51% of males and 64% of females and was more prevalent in endurance-trained athletes (males 58%, females 72%, p<0.001). The mean SBP/W-slope was lower in males (0.24±0.10 mmHg/W) than females (0.27±0.12 mmHg/W), p=0.031. In both sexes, peak oxygen uptake (VO2peak) was inversely correlated with SBP/W-slope (p<0.01). Those with an exaggerated SBPmax and below-median SBP/W-slope were 10 years younger and had a 20% higher VO2peak, on average (p<0.001). A non-exaggerated SBPmax and above-median SBP/W-slope was observed in older individuals with the lowest VO2peak.

Conclusion: In a large cohort of healthy individuals, an exaggerated SBPmax was common and associated with higher fitness. In contrast, higher SBP indexed to workload was associated with older age, lower fitness, and female sex. Thus, sex, age and fitness should be considered when evaluating BP response to exercise.

Aims: We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia.

Methods: In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting, competing risk models, and shared frailty models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of the association between therapeutic targets of hypnotics and cardiovascular diseases.

Results: During a median follow-up of 14.3 years, the matched cohort documented a total of 929 CHD cases, 360 HF cases, 262 stroke cases, and 180 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality. The inverse probability of treatment weighting, competing risk models, and shared frailty models didn't alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health.

Conclusions: Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Both observational and genetic evidence raised safety concerns regarding the cardiovascular impact of benzodiazepines. No cardiovascular hazard of Z-meds was discovered in the UKB population with insomnia.

In recent years, major advances in our understanding of risk factors implicated in the development of cardiovascular disease (CVD), in available tools for early detection of CVD, and in effective interventions to prevent subclinical or clinically manifest disease, have led to an increasing appreciation of prevention as a major pillar of cardiovascular medicine. Preventive cardiology has evolved into a dynamic sub-specialty focused on the promotion of cardiovascular health through all stages of life, and on the management of individuals at risk of developing CVD or experiencing recurrent cardiovascular events, through interdisciplinary care in different settings. As the level of knowledge, specialized skills, experience, and committed attitudes related to cardiovascular prevention has exceeded core cardiology training, the European Association of Preventive Cardiology (EAPC) has placed major emphasis on continuous education and training of physicians and allied professionals involved in cardiovascular prevention, with the aim of setting standards for practice and improving quality of care. The EAPC recognizes the need for comprehensive educational offer across different levels of training (from core cardiology to sub-specialty to expert training) as well as the need for interdisciplinary approaches that will promote synergies among allied professionals involved in cardiovascular prevention. This statement by the EAPC aims to highlight current gaps and unmet needs, and to describe the framework to help standardize, structure, and deliver comprehensive, up-to-date, interactive, high-quality education using a combination of traditional and novel educational tools. The document aims to form the basis for ongoing refinements of the EAPC educational offer, with the ultimate goal to ensure that new evidence in the field will translate to better cardiovascular practice and improved outcomes for our patients.