Alcohol and the heart: to abstain or not to abstain?

Alcohol has been consumed by most societies over the last 7000 years. Abraham Lincoln said It has long been recognized that the problems with alcohol relate not to the use of a bad thing, but to the abuse of a good thing. Light to moderate alcohol consumption reduces the incidence of coronary heart disease (CHD), ischemic stroke, peripheral arterial disease, CHD mortality, and all-cause mortality, especially in the western populations. However, heavy alcohol consumption is detrimental causing cardiomyopathy, cardiac arrhythmias, hepatic cirrhosis, pancreatitis, and hemorrhagic stroke. In this article, we review the effects of alcohol on CHD, individual cardiovascular risk factors, cardiomyopathy, and cardiac arrhythmias, including the most recent evidence of the effects of alcohol on CHD

Oral Apolipoprotein A-I Mimetic D-4F Lowers HDL-Inflammatory Index in High-Risk Patients: A First-in-Human Multiple-Dose, Randomized Controlled Trial.

A single dose of the apolipoprotein (apo)A-I mimetic peptide D-4F rendered high-density lipoprotein (HDL) less inflammatory, motivating the first multiple-dose study. We aimed to assess safety/tolerability, pharmacokinetics, and pharmacodynamics of daily, orally administered D-4F. High-risk coronary heart disease (CHD) subjects added double-blinded placebo or D-4F to statin for 13 days, randomly assigned 1:3 to ascending cohorts of 100, 300, then 500 mg (n = 62; 46 men/16 women). D-4F was safe and well-tolerated. Mean ± SD plasma D-4F area under the curve (AUC, 0-8h) was 6.9 ± 5.7 ng/mL*h (100 mg), 22.7 ± 19.6 ng/mL*h (300 mg), and 104.0 ± 60.9 ng/mL*h (500 mg) among men, higher among women. Whereas placebo dropped HDL inflammatory index (HII) 28% 8 h postdose (range, 1.25-0.86), 300-500 mg D-4F effectively halved HII: 1.35-0.57 and 1.22-0.63, respectively (P \u3c 0.03 vs. placebo). Oral D-4F peptide dose predicted HII suppression, whereas plasma D-4F exposure was dissociated, suggesting plasma penetration is unnecessary. In conclusion, oral D-4F dosing rendered HDL less inflammatory, affirming oral D-4F as a potential therapy to improve HDL function

Mitral annular dynamics in mitral annular calcification : a three-dimensional imaging study

Background: The mitral annulus displays complex conformational changes during the cardiac cycle that can now be quantified by three-dimensional echocardiography. Mitral annular calcification (MAC) is increasingly encountered, but its structural and dynamic consequences are largely unexplored. The objective of this study was to describe alterations in mitral annular dimensions and dynamics in patients with MAC. Methods: Transthoracic three-dimensional echocardiography was performed in 43 subjects with MAC and 36 age- and sex-matched normal control subjects. Mitral annular dimensions were quantified, using dedicated software, at six time points (three diastolic, three systolic) during the cardiac cycle. Results: In diastole, the calcified annulus was larger and flatter than normal, with increased anteroposterior diameter (29.4 6 0.6 vs 27.8 6 0.6 mm, P = .046), reduced height (2.8 6 0.2 vs 3.6 6 0.2 mm, P = .006), and decreased saddle shape (8.9 6 0.6% vs 11.4 6 0.6%, P = .005). In systole, patients with MAC had greater annular area at all time points (P < .05 for each) compared with control subjects, because of reduced contraction along the anteroposterior diameter (P < .001). Saddle shape increased in early systole (from 10.5% to 13.5%, P = .04) in control subjects but not in those with MAC (P = NS). Valvular alterations were also noted; although mitral valve tent length decreased during systole in both groups, decreases were less in patients with MAC (P < .05 for mid- and late systole). For certain parameters (e.g., annular area), changes were confined largely to those patients with moderate to severe MAC (P = .006 vs control subjects, but nonsignificant for patients with mild MAC). Conclusions: Quantitative three-dimensional echocardiography provides new insights into the dynamic consequences of MAC. This imaging technique demonstrates that the mitral annulus is not made smaller by calci- fication. However, there is loss of annular contraction, particularly along the anteroposterior diameter, and loss of early systolic folding along the intercommissural diameter. Associated valvular alterations include smaller than usual declines in tenting during systole. These quantitative three-dimensional echocardiographic data provide new insights into the dynamic physiology of the calcified mitral annulus. (J Am Soc Echocardiogr 2015;28:786-94.

Safety, pharmacokinetics, and pharmacodynamics of oral apoA-I mimetic peptide D-4F in high-risk cardiovascular patients*

Patients with coronary heart disease or equivalent risk received a single dose of 30, 100, 300, or 500 mg of unformulated D-4F (n = 8, each dose) or placebo (n = 8) under fasting conditions. An additional 10 patients received 500 mg (n = 8) or placebo (n = 2) with a low-fat meal. There were no significant trends in any safety parameter. D-4F was detectable in plasma at all doses with a Tmax of 30 min, 1 h, and 2 h for 30, 100, and ⩾ 300 mg, respectively. The area under the curve(0−t) was 27.81 ng/hr/ml and 54.71 ng/hr/ml for the 300 mg and 500 mg dose groups, respectively, and 17.96 ng/hr/ml for the 500mg dose given with food. HDL from each time point for each subject was tested for its ability to inhibit LDL-induced monocyte chemotactic activity in cultures of human aortic endothelial cells. The values obtained were normalized to 1.0 for LDL alone to obtain the HDL inflammatory index. This index significantly improved at 4 h at the 300 mg dose and at 2 h at the 500 mg dose compared with placebo (P < 0.05). There were no changes in plasma lipid or lipoprotein levels. We conclude that unformulated D-4F has low bioavailability that is improved under fasting conditions, and that a single dose of D-4F is safe and well tolerated and may improve the HDL anti-inflammatory index