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Highlighted articles July

Volume 274 Issue July 2018

By Simona Negrini and Arnold von Eckardstein (Editor–in-Chief).

This issue of Atherosclerosis contains several observational and interventional studies that demonstrate the importance of lifestyle factors such as smoking, body weight, physical activity, and sleep for the determination of cardiovascular risk even in individuals with well controlled LDL-cholesterol levels.

Issue highlights

Articles on lifestyle factors

    Highlighted articles

    The prevalence and correlates of subclinical atherosclerosis among adults with low-density lipoprotein cholesterol <70 mg/dL: The Multi-Ethnic Study of Atherosclerosis (MESA) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

    The prevalence and correlates of subclinical atherosclerosis when low-density lipoprotein cholesterol (LDL-C) levels are low remain unclear. Al Rifai et al. examined the association of cardiovascular risk factors with subclinical atherosclerosis among individuals with untreated LDL-C <70 mg/dL.

    They included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohorts. To optimize accuracy, LDL-C was calculated by the validated Martin/Hopkins equation that uses an adjustable factor for the ratio of triglycerides to very low-density lipoprotein cholesterol. Subclinical atherosclerosis was defined as a coronary artery calcium (CAC) score >0 in the combined cohort or common carotid intima media thickness (cIMT) in the 4th quartile, using cohort-specific cIMT distributions at baseline. The cross-sectional association of cardiovascular risk factors and subclinical atherosclerosis was assessed with logistic regression models.

    Among 9411 participants not on lipid lowering therapy, 263 had LDL-C <70 mg/dL. Mean age was 58 years, with 43% men, and 41% Black. The prevalence of CAC >0 in subjects with untreated LDL-C <70 mg/dL was 30%, and 18% were in the 4th quartile of cIMT. In demographically adjusted models, only ever smoking was significantly associated with both CAC and cIMT. Similar results were obtained with risk factor-adjusted models.

    Among middle-aged to older individuals with untreated LDL-C <70 mg/dL, subclinical atherosclerosis remains moderately common and is associated with cigarette smoking.

    Non-LDL dyslipidemia is prevalent in the young and determined by lifestyle factors and age: The LifeLines cohort

    Development of atherosclerotic cardiovascular disease (ASCVD) is strongly determined by modifiable risk factors such as dyslipidemia. Non-LDL dyslipidemia (NLD), including low levels of high-density lipoprotein cholesterol (HDLc), elevated triglycerides (TG), or high remnant cholesterol (Rc), is associated with increased risk of developing ASCVD, and prevalence rates appear to be high in elderly populations. Small cohorts have identified several lifestyle, anthropometric, and medical factors associated with NLD. de Vries et al. assessed sex- and age-specific prevalence of NLD in a contemporary population cohort and explored independent determinants of NLD, focusing on lifestyle, anthropometric, and medical factors.

    The prevalence of NLD was determined per 10-year age intervals in adults without cardiovascular disease not using lipid-modifying drugs from the Dutch LifeLines cohort, a large, prospective, population-based cohort study with a 3-generational design, examining health and health-related behaviours in a representative sample of subjects from the North Netherlands. NLD was defined as low HDL-cholesterol or high triglycerides or high remnant cholesterol as per guideline cut-off values. Multivariable regression was used to identify factors independently associated with NLD. Determinants included age, smoking, alcohol use, physical activity, diet, BMI, diabetes mellitus (DM), chronic kidney disease, and in women, menopausal state and oral contraceptive use.

    The results show that NLD occurred in 15–19% of women and 13–30% of men, with the highest prevalence in 35–55 year old men. In most age groups, the prevalence in women was lower than in men. Obesity, current smoking, and diabetes were strongly associated with NLD.

    NLD occurs frequently at an early age. Modifiable lifestyle choices, obesity, and diabetes are strong determinants of NLD.

    Associations of body weight and weight change with cardiovascular events and mortality in patients with coronary heart disease

    It is recommended that patients with coronary heart disease (CHD) pursue a normal body weight, while the effects of body weight and weight change on prognosis are still controversial. In this study, Dong et al. assessed these effects using a large-scale population of 5276 patients with CHD in China.

    Baseline and endpoint weights were measured. Outcomes, including mortality and cardiovascular events, were obtained.

    Relative to patients with normal weight, risks for adverse outcomes were lowest in overweight patients and similar in obese patients. Hazard ratios (HRs) for all-cause death were 1.42 if overweight turned into normal weight and 2.01 and 5.33 if obese turned into overweight and normal weight, respectively. Death risk increased with the extent of weight loss and moderate or large weight gain. Similar results were found when risks for cardiovascular mortality and events were considered. Furthermore, these results remained significant when the patients were stratified by several covariates and even when several definitions of weight change were considered.

    Obesity did not increase adverse outcome risks in patients with CHD. Both weight loss and weight gain increased the adverse outcome risks regardless of baseline body weight. The findings suggest that maintaining a stable weight may be a better strategy for the reduction of risks for cardiovascular outcomes and all-cause death in patients with CHD.

    HDL cholesterol efflux capacity and cholesteryl ester transfer are associated with body mass, but are not changed by diet-induced weight loss: A randomized trial in abdominally obese men

    Obesity is associated with a lower HDL-mediated cholesterol efflux from macrophages and a higher CETP (cholesteryl ester transfer protein) activity, but effects of weight loss are not clear. In addition, associations with visceral and subcutaneous adipose tissue are not known. Talbot et al. investigated the effects of diet-induced weight loss on HDL-mediated cholesterol efflux and cholesterol ester (CE) transfer in abdominally obese men. Differences between normal-weight and abdominally obese men were also examined.

    Twenty-five apparently healthy, normal-weight men and 52 abdominally obese men were included. Abdominally obese subjects were randomly allocated to a dietary weight-loss intervention group or a no–weight loss control group. Individuals from the intervention group followed a very-low-calorie diet for 6 weeks to obtain a waist circumference below 102 cm, followed by a 2-week weight-stable period.

    Cholesterol efflux was measured in BODIPY-labeled murine J774 macrophages. CE transfer was measured by quantifying the transfer of CE from radiolabeled exogenous HDL to apoB-containing lipoproteins.

    Cholesterol efflux capacity was 9 percentage point (pp) lower in abdominally obese than in normal-weight men while CE transfer was 5 pp higher. Diet-induced weight-loss of 10.3 kg did not change cholesterol efflux and CE transfer. In addition, stepwise regression analysis did not suggest that the different fat depots are differently related to efflux capacity and CE transfer.

    After a 2-week weight-stable period, dietary weight loss of 10 kg did not improve ABCA1-mediated cholesterol efflux and CE transfer in abdominally obese men. Two weeks of weight stable may be too short to observed effects on these parameters.

    Aerobic, resistance or combined training: A systematic review and meta-analysis of exercise to reduce cardiovascular risk in adults with metabolic syndrome

    Exercise is beneficial to individuals with metabolic syndrome (MetS). An understudied group, who represent the majority of the MetS population, are individuals who have not developed diabetes. Wewege et al. examined aerobic, resistance and combined (aerobic + resistance) exercise for cardiovascular risk factors in MetS without diabetes.

    Eight electronic databases were searched up to September 2017 for randomised controlled trials >4 weeks long that compared an exercise intervention to the non-exercise control in MetS without diabetes. MetS criteria, cardiorespiratory fitness and cardiovascular risk factors were meta-analysed in a random effects model.

    Eleven studies with 16 interventions were included. Aerobic exercise significantly improved waist circumference, fasting glucose , high-density cholesterol, triglycerides , diastolic blood pressure , and cardiorespiratory fitness, among other outcomes. No significant effects were determined following resistance exercise, possibly due to limited data. Sub-analyses suggested that aerobic exercise progressed to vigorous intensity, and conducted 3 days/week for ≥12 weeks offered larger and more widespread improvements.

    Aerobic exercise following current guidelines offers widespread benefits to individuals with MetS without diabetes. More studies on resistance/combined exercise programs in MetS are required to improve the quality of evidence.

    Effects of high-intensity interval training on optic nerve head and macular perfusion using optical coherence tomography angiography in healthy adults

    High-intensity interval training (HIIT) has been found to be efficient in increasing health-related fitness in general and in lifestyle-induced chronic diseases such as hypertension, obesity and metabolic syndrome. Schmitz et al. aimed to evaluate HIIT effects on optic nerve head (ONH) and macular perfusion in healthy adults using optical coherence tomography angiography (OCTA).

    Fifty-eight healthy participants performed a 4-week HIIT, with two exercise sessions/week: Group 1, 4 × 30 HIIT, running at maximal speed (all-out) for 4 × 30 s with 30 s active recovery, Group 2, 8 × 15 HIIT, running at maximal speed (all-out) for 8 × 15 s with 15 s active recovery. OCTA of the ONH and the macula was performed at baseline and follow-up to detect changes of the foveal avascular zone (FAZ). Flow density was evaluated in the superficial and deep plexus of the central macula, in the radial peripapillary capillary layer, and the nerve head layer of the disc region and of the peripapillary region.

    The mean deep FAZ area and flow density of the superficial layer decreased in response to overall HIIT. The flow density of the nerve head layer in the peripapillary area showed an overall increase. All other parameters showed no difference.

    HIIT may be performed to induce changes in ophthalmic measures such as FAZ and nerve head perfusion. OCTA imaging of the central retina and the ONH could represent a sensitive tool for the early detection of systemic vascular changes.

    Sleep duration and subclinical atherosclerosis: The Aragon Workers' Health Study

    Few studies have evaluated the association of sleep duration with subclinical atherosclerosis, with heterogeneous findings. Blasco-Colmenares evaluated the association of sleep duration with the presence of coronary, carotid, and femoral subclinical atherosclerosis in healthy middle-age men with low prevalence of clinical comorbidities.

    They performed a cross-sectional analysis of 1968 men, 40–60 years of age, participating in the Aragon Workers' Health Study (AWHS), an ongoing prospective longitudinal cohort study designed to characterize the association of traditional and emergent CVD risk factors with the prevalence and progression of subclinical atherosclerosis in apparently healthy middle-aged workers in an automobile assembly plant in Spain. Duration of sleep during a typical work week was assessed by questionnaire. Coronary artery calcium scores (CACS) was assessed by computed tomography and the presence of carotid plaque and femoral plaque by ultrasound.

    In fully adjusted models, the odds ratios for CACS >0 comparing sleep durations of ≤5, 6, and ≥8 h with 7 h were 1.34, 1.35 and 1.21, respectively. A similar U-shaped association was observed for CACS ≥100 and for CACS. The corresponding odds ratios for the presence of at least one carotid plaque were 1.23, 1.09, and 0.86, respectively, and for the presence of at least one femoral plaque were 1.25, 1.19 and 1.17, respectively.

    Middle-aged men reporting 7 h of sleep duration had the lowest prevalence of subclinical coronary atherosclerosis as assessed by CACs. Our results support that men with very short or very long sleep durations are at increased risk of atherosclerosis.

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