Alcohol type and ideal cardiovascular health among adults of the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Light to moderate alcohol consumption is associated with favorable cardiovascular health (CVH). However, the association between alcohol type and ideal CVH has not been well-established. We examined the relationship between alcohol type and ideal CVH as measured by the American Heart Association's seven CVH metrics. METHODS: We analyzed data from 6,389 men and women aged 45-84 years from a multi-ethnic cohort free of cardiovascular disease. Alcohol type (wine, beer and liquor) was categorized as never, former, 0 but drink other alcohol types, >0 but <1 drink/day, 1-2 drinks/day and >2 drinks/day. A CVH score ranging from 0 to 14 points was created from the seven CVH metrics (Inadequate score, 0-8; average, 9-10; optimal, 11-14). We used multinomial logistic regression to examine the association between alcohol type and CVH, adjusting for age, sex, race/ethnicity, education, income, health insurance, field site and total calorie intake. RESULTS: The mean (SD) age of participants was 62 (10) years and 53 % were women. Participants who consumed 1-2 drinks/day of wine had higher odds of optimal CVH scores compared to those who never drank wine [adjusted prevalence odds ratio (POR) 1.64 (1.12-2.40)]. In comparison to participants who never drank beer, those who consumed >2 drinks/day of beer had lower odds of optimal CVH scores [0.31 (0.14-0.69)]. Additionally, those who consumed >2 drinks/day of liquor had lower odds of optimal scores compared to those who never drank liquor [0.32 (0.16-0.65)]. CONCLUSION: Moderate consumption of wine was associated with favorable CVH. However, heavy consumption of beer or liquor was associated with poorer CVH.

Non-Alcoholic Fatty Liver Disease Modifies Serum Gamma-Glutamyl Transferase in Cigarette Smokers.

BACKGROUND: Serum gamma-glutamyl transferase (GGT) is a marker of oxidative stress, associated with increased cardiovascular (CV) risk. The impact of smoking on oxidative stress may be aggravated in individuals with non-alcoholic fatty liver disease (NAFLD). We aimed to ascertain the association of smoking on GGT levels in the presence or absence of NAFLD. METHODS: We evaluated 6,354 healthy subjects (43 ± 10 years, 79% males) without clinical cardiovascular disease (CVD) undergoing an employer-sponsored physical between December 2008 and December 2010. NAFLD was diagnosed by ultrasound and participants were categorized as current or non-smokers by self report. A multivariate linear regression of the cross-sectional association between smoking and GGT was conducted based on NAFLD status. RESULTS: The prevalence of NAFLD was 36% (n = 2,299) and 564 (9%) were current smokers. Smokers had significantly higher GGT levels in the presence of NAFLD (P < 0.001). After multivariable adjustment, current smoking was associated with 4.65 IU/L higher GGT level, P < 0.001, compared to non-smokers. When stratified by NAFLD, the magnitude of this association was higher in subjects with NAFLD (ß-coefficient: 11.12; 95% confidence interval (CI): 5.76 - 16.48; P < 0.001); however, no such relationship was observed in those without NAFLD (ß: -0.02; 95% CI: -3.59, 3.56; P = 0.992). Overall the interaction of NAFLD and smoking with GGT levels as markers of oxidative stress was statistically significant. CONCLUSIONS: Smoking is independently associated with significantly increased oxidative stress as measured by GGT level. This association demonstrates effect modification by NAFLD status, suggesting that smoking may intensify CV risk in individuals with NAFLD.

Benefits and Risks of Continuing Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Antagonists, and Mineralocorticoid Receptor Antagonists during Hospitalizations for Acute Heart Failure.

BACKGROUND: The renin-angiotensin-aldosterone axis plays a pivotal role in the pathophysiology of acute and chronic heart failure (HF) and represents an important target for guideline-directed medical therapy. SUMMARY: The use of appropriate directed medical therapies for inhibition of the renin-angiotensin-aldosterone axis in chronic HF has been the subject of several landmark clinical trials, with high levels of adherence exhibited in the outpatient setting. However, less clarity exists with respect to the initiation, continuation, and cessation of renin-angiotensin-aldosterone system inhibitors (RAASi) in the setting of acute HF and exacerbation of HF necessitating hospitalization. In this review, we summarize relevant aspects of the physiology of the renin-angiotensin-aldosterone axis in acute HF and during decongestion. We also summarize the available evidence for the risks and benefits of initiating and continuing RAASi in acute HF. Key Message: We offer a decision-making pathway for the use of RAASi in the setting of acute HF that would help guide the cardiologist and nephrologist caring for patients with acute HF and cardiorenal syndrome.

The relationship of erectile dysfunction and subclinical cardiovascular disease: A systematic review and meta-analysis.

Erectile dysfunction (ED) is associated with cardiovascular disease (CVD) and CVD mortality. However, the relationship between ED and subclinical CVD is less clear. We synthesized the available data on the association of ED and measures of subclinical CVD. We searched multiple databases for published literature on studies examining the association of ED and measures of subclinical CVD across four domains: endothelial dysfunction measured by flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), coronary artery calcification (CAC), and other measures of vascular function such as the ankle-brachial index, toe-brachial index, and pulse wave velocity. We conducted random effects meta-analysis and meta-regression on studies that examined an ED relationship with FMD (15 studies; 2025 participants) and cIMT (12 studies; 1264 participants). ED was associated with a 2.64 percentage-point reduction in FMD compared to those without ED (95% CI: -3.12, -2.15). Persons with ED also had a 0.09-mm (95% CI: 0.06, 0.12) higher cIMT than those without ED. In subgroup meta-analyses, the mean age of the study population, study quality, ED assessment questionnaire (IIEF-5 or IIEF-15), or the publication date did not significantly affect the relationship between ED and cIMT or between ED and FMD. The results for the association of ED and CAC were inconclusive. In conclusion, this study confirms an association between ED and subclinical CVD and may shed additional light on the shared mechanisms between ED and CVD, underscoring the importance of aggressive CVD risk assessment and management in persons with ED.

Elevated gamma-glutamyl transferase is associated with subclinical inflammation independent of cardiometabolic risk factors in an asymptomatic population: a cross-sectional study.

BACKGROUND: Serum Gamma-Glutamyl Transferase (GGT), a marker of oxidative stress, has been suggested to be independently associated with cardiovascular disease (CVD) events. We examined the association of serum GGT levels with the burden of subclinical inflammation across a spectrum of metabolic conditions. METHODS: We evaluated 5,446 asymptomatic subjects (43 ± 10 years, 78 % males) who had an employer-sponsored physical between 2008 and 2010. Highly sensitivity C-reactive protein (hsCRP) was measured as a marker of underlying systemic inflammation. A linear regression of GGT quartiles with log transformed hsCRP and a multivariate logistic regression of GGT quartiles with elevated hsCRP (≥3 mg/L) were performed. RESULTS: Median GGT was 31 IU/l (IQR: 22-45 IU/l), 1025 (19 %) had hsCRP ≥ 3 mg/L. The median hsCRP increased with GGT quartiles (Q1: 0.9 mg/L, Q2: 1.1 mg/L, Q3: 1.4 mg/L, Q4: 1.6 mg/L, p < 0.001). Linear regression models showed GGT in the fourth quartile was associated with 0.45 mg/L (95 % CI 0.35, 0.54, p < 0.001) increase in log transformed hsCRP adjusting for risk factors. The Odds Ratio (OR) for an elevated hsCRP (≥3 mg/L) also increased with higher GGT quartiles; GGT Q2 1.44 (95 % CI 1.12, 1.85), GGT Q3 1.89 (95 % CI 1.45, 2.46), GGT Q4 2.22 (95 % CI 1.67, 2.95), compared to GGT Q1. The strength of association increased in the presence of and combination of metabolic conditions. CONCLUSION: In our cohort of asymptomatic individuals a higher serum GGT level was independently associated with increased burden of subclinical inflammation across metabolic states. These findings may explain GGT association with increased CVD risk.

Obesity Modifies the Effect of Fitness on Heart Rate Indices during Exercise Stress Testing in Asymptomatic Individuals.

OBJECTIVE: To assess the impact of aerobic fitness on exercise heart rate (HR) indices in an asymptomatic cohort across different body mass index (BMI) categories. METHODS: We performed a cross-sectional analysis of 506 working-class Brazilian subjects, free of known clinical cardiovascular disease(e.g. ischemic heart disease and stroke) who underwent an exercise stress test. RESULTS: There was a significant trend towards decreased HR at peak exercise, HR recovery and chronotropic index (CI) measures as BMI increased, but resting HR increased significantly across BMI categories. In multivariate analysis, the change in CI per unit change in metabolic equivalents of task was greater among the obese subjects than the normal-weight (2.7 vs. ­0.07; p interaction = 0.029)and overweight (2.7 vs. 0.7; p interaction = 0.044) subjects. A similar pattern was seen with peak HR and HR recovery, although the formal tests of interaction did not achieve statistical significance. CONCLUSION: Our findings strongly suggest that fitness is associated with a favorable HR profile and is modified by BMI. Intervention programs should place emphasis on fitness and not only on weight loss.

Blood pressure is associated with the presence and severity of nonalcoholic fatty liver disease across the spectrum of cardiometabolic risk.

OBJECTIVES: To determine the relationship between clinically relevant blood pressure (BP) groups and nonalcoholic fatty liver disease (NAFLD) presence and severity especially in the milieu of other metabolic risk factors. PATIENTS AND METHODS: From a Brazilian cohort of 5362 healthy middle-aged men and women who presented for yearly physical examination and testing, the cross-sectional relationship between BP categories and NAFLD was assessed. BP groups were categorized as normal, prehypertension (PHT), and hypertension (HTN) according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure classification. NAFLD was ultrasound diagnosed, excluding persons with alcohol consumption more than 20 g/day. NAFLD severity was estimated using the Fibrosis-4 (FIB-4) risk score. RESULTS: The prevalence of NAFLD was 36.2%. Participants with NAFLD were older (mean 46 vs. 42 years, P < 0.001) and had elevated BMI (mean 29.0 vs. 24.7 kg/m, P < 0.001). The prevalence of NAFLD among persons with normal BP, PHT, and HTN was 16.5, 37.5, and 59.3%, respectively. In multivariate analyses, PHT and HTN were associated with elevated odds of NAFLD (PHT-adjusted odds ratio 1.3, 95% confidence interval 1.1, 1.6; HTN-adjusted odds ratio 1.8, 95% confidence interval 1.4-2.3) compared with normal BP. Among nonobese hypertensive patients, BP control (BP < 140/90 mmHg) was independently associated with 40% lower odds of prevalent NAFLD. Compared with hypertensive patients, both normotensive individuals and prehypertensive patients were more likely to have a low fibrosis risk (FIB-4 ≥ 1.3). CONCLUSION: Prevalent NAFLD may be seen early in the development of hypertension, even in the absence of other metabolic risk factors. Controlling BP among nonobese hypertensive patients may be beneficial in preventing or limiting NAFLD.

Relation of physical activity to prevalence of nonalcoholic Fatty liver disease independent of cardiometabolic risk.

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance and has been linked with increased cardiovascular risk. Although physical activity (PA) and lifestyle modification are often recommended in patients at cardiovascular risk, the benefit across the cardiometabolic risk spectrum is unclear. We aimed to evaluate the relation of PA and NAFLD independent of metabolic syndrome (MS) or obesity. We evaluated 5,743 healthy Brazilian subjects (43 ± 10 years, 79% men) without clinical coronary heart disease from December 2008 to December 2010. NAFLD was diagnosed using ultrasounds, and self-reported PA was assessed using the International Physical Activity Questionnaire scale. In a multivariate logistic regression adjusted for cardiometabolic risk factors, we evaluated for an independent association of NAFLD and PA. In the total study population, NAFLD prevalence was 36% (n = 2,075), obesity 23% (1,300), and MS 20% (1,152). NAFLD was more prevalent in subjects with MS (74%) than those without (26%) and in those obese (73%) than in those nonobese (25%). Overall, 1,305 (23%) subjects reported low activity, 1,990 (35%) moderate activity, and 2,448 (42%) high activity. NAFLD prevalence was lower at higher levels of reported PA (low 45%, moderate 38%, and high 30%, p <0.001). After adjusting for risk factors, subjects with high activity had lower odds of having NAFLD. The favorable association was independent of obesity or MS. In conclusion, PA presents a dose-response association with NAFLD independent of the MS or obesity. Our results are compatible with the idea that benefits of PA are relevant to everyone regardless of cardiometabolic risk.

Systematic review on noninvasive assessment of subclinical cardiovascular disease in obstructive sleep apnea: new kid on the block!

Patients with obstructive sleep apnea (OSA) have a high burden of cardiovascular disease (CVD) but a causal relationship between OSA and atherosclerotic CVD remains unclear. We systematically reviewed the literature analyzing the relationship. A review of the Medline database for studies noninvasively evaluating subclinical CVD in OSA was conducted. A total of fifty-two studies were included in this review. Across the studies the prevalence of atherosclerosis, as assessed by coronary artery calcification, carotid intima-media thickness, brachial artery flow-mediated dilation and pulse wave velocity was higher in patients with OSA and correlated with increasing severity and duration of OSA. This study shows OSA is an independent predictor of subclinical CVD as CVD is more likely to occur in patients with long standing and severe OSA. Further research is however necessary to identify specific OSA populations that would benefit from aggressive screening.

Statin use is not associated with presence of and severity of nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: There is concern that statin use may exacerbate nonalcoholic fatty liver disease (NAFLD). We aimed to assess the association of statin use with NALFD and severity of liver fibrosis among NAFLD individuals. METHODS: We evaluated 6,385 cross-sectional healthy Brazilian subjects (43 ± 10 years, 79% males) without clinical coronary heart disease between November 2008 and July 2010. NAFLD was diagnosed by ultrasound. Severity of liver fibrosis was predicted by fatty liver index and FIB-4. RESULTS: NAFLD prevalence was 36% (n = 2310). Overall 552 (9%) individuals were using statins of whom 49% had NAFLD. Statin users were more likely to be men, older age, and have higher burden of risk factors (p <0.05). In age gender adjusted analysis the odds ratio for NAFLD with statin use was 0.87 (0.61-1.25, p = 0.46) in the presence of metabolic syndrome and 1.08 (0.88-1.32, p = 0.56) in its absence. On further adjustment for metabolic risk factors, LDL and smoking the results remained unchanged (OR: 0.89, 95% CI: 0.65-1.32, p = 0.56 and 0.90 (0.69-1.18, p = 0.46). There was no significant association between statin use and fatty liver index in a subanalysis of NAFLD individuals (71 ± 18 vs. 69 ± 23, p = 0.18). Although FIB-4 was mildly elevated with statin use (1.20 ± 0.51 vs. 1.02 ± 0.46, p <0.001), a multivariate analysis adjusted for age, gender and risk factors revealed statin use was not associated with severe fibrosis (FIB >1.45) (OR 0.88, 95% CI: 0.60-1.29, p = 0.50). CONCLUSIONS: The results of this study favor statin use in subjects with NAFLD as its use is not associated with the presence of NAFLD or increased fibrosis.

A systematic review: burden and severity of subclinical cardiovascular disease among those with nonalcoholic fatty liver; should we care?

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an emerging disease and a leading cause of chronic liver disease. The prevalence in the general population is approximately 15-30% and it increases to 70-90% in obese or diabetic populations. NAFLD has been linked to increased cardiovascular disease (CVD) risk. It is therefore critical to evaluate the relationship between markers of subclinical CVD and NAFLD. METHOD: An extensive search of databases; including the National Library of Medicine and other relevant databases for research articles meeting inclusion criteria: observational or cohort, studies in adult populations and clearly defined NAFLD and markers of subclinical CVD. RESULTS: Twenty-seven studies were included in the review; 16 (59%) presented the association of NAFLD and carotid intima-media thickness (CIMT), 7 (26%) the association with coronary calcification and 7 (26%) the effect on endothelial dysfunction and 6 (22%) influence on arterial stiffness. CIMT studies showed significant increases among NAFLD patients compared to controls. These were independent of traditional risk factors and metabolic syndrome. The association was similar in coronary calcification studies. The presence of NAFLD is associated with the severity of the calcification. Endothelial dysfunction and arterial stiffness showed significant independent associations with NAFLD. Two studies argued the associations were not significant; however, these studies were limited to diabetic populations. CONCLUSION: There is evidence to support the association of NAFLD with subclinical atherosclerosis independent of traditional risk factors and metabolic syndrome. However, there is need for future longitudinal studies to review this association to ascertain causality and include other ethnic populations.