Alcohol consumption and abnormalities of brain structure and vasculature

Research on how alcohol consumption influences the structure and blood supply of the brain has generally focused on two primary areas of interest: the atrophic effect of heavy drinking on brain structure and the effects of moderate and heavy drinking on the risk of stroke. Heavy alcohol consumption results in atrophy of gray and white matter, particularly in the frontal lobes, cerebellum, and limbic structures. Heavy drinking also raises the risk of ischemic and hemorrhagic stroke, while light drinking is associated with a lower risk of ischemic stroke. Recently, the author and his colleagues studied alcohol consumption and prevalence of subclinical abnormalities detected by magnetic resonance imaging of the brain among 3376 older adults enrolled in the Cardiovascular Health Study. They found that alcohol consumption was positively associated with measures of brain atrophy and inversely associated with subclinical infarcts in a dose-dependent manner. Alcohol consumption and white matter lesions had a U-shaped relationship, with the lowest prevalence among those who consumed 1–6 drinks per week. Further research is needed to determine how these associations interact to influence overall brain function.     

Alcohol consumption and coronary atherosclerosis progression--the Stockholm Female Coronary Risk Angiographic Study

OBJECTIVE: To assess the association of alcohol intake with progression of coronary atherosclerosis. Although moderate drinkers have a lower risk of coronary heart disease than abstainers, the relation of alcohol use and coronary atherosclerosis has not been well studied. METHODS AND RESULTS: In the Stockholm Female Coronary Risk Angiographic Study, we evaluated 103 women, aged 65 years or younger, hospitalized with acute myocardial infarction or unstable angina pectoris who underwent serial quantitative coronary angiography 3-6 months following their index event and repeated an average of 3 years and 3 months (range 2-5 years) later. Individual alcoholic beverage consumption was assessed by a standardized questionnaire. We used mixed model analysis to estimate the effect of alcohol consumption on progression of coronary atherosclerosis, as measured by mean luminal diameter change, controlling for age, smoking, body-mass index, education, physical activity, index cardiac event, menopausal status, diabetes, and history of dyslipidemia. Of the 93 women with complete information on alcohol intake, 14 consumed no alcohol (abstainers), 55 consumed up to 5 g of alcohol per day (light drinkers), and 24 consumed more than 5 g of alcohol per day (moderate drinkers). Coronary atherosclerosis progressed by a multivariate-adjusted average of 0.138 mm (95% confidence interval (CI): 0.027-0.249) among abstainers, 0.137 mm (95% CI: 0.057-0.217) among light drinkers, and -0.054 mm (95% CI: -0.154 to 0.047) among moderate drinkers (P < 0.001). The inverse association persisted in analyses stratified by index event. No beverage type appeared to confer particular benefit. CONCLUSIONS: Among middle-aged women with coronary heart disease, moderate alcohol consumption (over 5 g/day) was protective of coronary atherosclerosis progression.     

Moderate alcohol consumption and safety of lovastatin and warfarin among men: the post-coronary artery bypass graft trial

Purpose

Although moderate drinking has been associated with lower mortality among patients with coronary heart disease, its safety among patients taking common cardiac medications is unknown.

Subjects and methods

We studied 1244 men enrolled in the Post-Coronary Artery Bypass Graft (CABG) Trial who had undergone previous coronary bypass surgery. Participants were randomly assigned to lovastatin in low (mean 4 mg) or high (mean 76 mg) doses and to low-dose warfarin (mean international normalized ratio [INR] 1.4, goal INR <2.0) or placebo in a factorial design. Participants underwent routine measurement of alanine aminotransferase (ALT) and INR levels every 6 to 12 weeks for 4 to 5 years. We categorized weekly alcohol intake as abstention (<1 drink), light (1-6 drinks), moderate (7-13 drinks), and heavier (≥14 drinks).

Results

During follow-up, 66% of men taking warfarin had an INR of 2.0 or higher, and 7% of men had an ALT of 80 IU/L or higher. Maximum INR (P = .72) and ALT (P = .51) levels did not differ across categories of alcohol intake. The risks of an INR of 2.0 or higher were 67%, 66%, 68%, and 61% among non-, light, moderate, and heavier drinkers (P = .86), respectively. The corresponding risks of an ALT of 80 IU/L or more were 8%, 10%, 9%, and 6% (P = .70), respectively.

Conclusion

Moderate drinking did not adversely influence the safety of low-dose warfarin or even high-dose lovastatin among men in this randomized trial, as measured by INR and ALT levels.     

Monounsaturated, trans, and saturated Fatty acids and cognitive decline in women

OBJECTIVES: To prospectively assess effects of select dietary fats on cognitive decline. DESIGN: Prospective observational; 3‐year follow‐up. SETTING: Northwestern University. PARTICIPANTS: Four hundred eighty‐two women aged 60 and older who participated in the Women's Health Initiative (WHI) Observational Study or in the control group of the WHI Diet Modification arm. MEASUREMENTS: Dietary intake from a validated food frequency questionnaire (FFQ) administered twice (mean 2.7 years apart) before baseline cognitive assessment (mean 2.9 years after second FFQ) was averaged. Testing of memory, vision, executive function, language, and attention was performed twice, 3 years apart. A global Z‐score was created for both time points by averaging all Z‐scores for each participant, and global cognitive change was defined as the difference between follow‐up and baseline Z‐scores. RESULTS: Median intake of saturated fat (SFA), trans‐fat, (TFA), dietary cholesterol (DC), and monounsaturated fat (MUFA) was 18.53, 3.45, 0.201, and 19.39 g/d, respectively. There were no associations between degree of cognitive decline and intake of SFA (P=.69), TFA (P=.54), or DC (P=.64) after adjusting for baseline cognition, total energy intake, age, education, reading ability, apolipoprotein E ?4 allele, body mass index, estrogen and beta‐blocker use, and intake of caffeine and other fatty acids. In contrast, MUFA intake was associated with lower cognitive decline in fully adjusted linear regression models, with mean decline (standard error) of 0.21 (0.05) in the lowest and 0.05 (0.05) in the highest quartiles (P=.02). This effect of MUFA intake was primarily in the visual and memory domains (P=.03 for both). CONCLUSION: Greater intake of SFA, TFA, and DC was not associated with cognitive decline, whereas greater MUFA intake was associated with less cognitive decline.     

Genetically Elevated Fetuin-A Levels,Fasting Glucose Levels,and Risk of Type 2 Diabetes: The Cardiovascular Health Study*

OBJECTIVE

Fetuin-A levels are associated with higher risk of type 2 diabetes, but it is unknown if the association is causal. We investigated common (>5%) genetic variants in the fetuin-A gene (AHSG) fetuin-A levels, fasting glucose, and risk of type 2 diabetes.

RESEARCH DESIGN AND METHODS

Genetic variation, fetuin-A levels, and fasting glucose were assessed in 2,893 Caucasian and 542 African American community-living individuals 65 years of age or older in 1992–1993.

RESULTS

Common AHSG variants (rs4917 and rs2248690) were strongly associated with fetuin-A concentrations (P < 0.0001). In analyses of 259 incident cases of type 2 diabetes, the single nucleotide polymorphisms (SNPs) were not associated with diabetes risk during follow-up and similar null associations were observed when 579 prevalent cases were included. As expected, higher fetuin-A levels were associated with higher fasting glucose concentrations (1.9 mg/dL [95% CI, 1.2–2.7] higher per SD in Caucasians), but Mendelian randomization analyses using both SNPs as unbiased proxies for measured fetuin-A did not support an association between genetically predicted fetuin-A levels and fasting glucose (−0.3 mg/dL [95% CI, −1.9 to 1.3] lower per SD in Caucasians). The difference between the associations of fasting glucose with actual and genetically predicted fetuin-A level was statistically significant (P = 0.001). Results among the smaller sample of African Americans trended in similar directions but were statistically insignificant.

CONCLUSIONS

Common variants in the AHSG gene are strongly associated with plasma fetuin-A concentrations, but not with risk of type 2 diabetes or glucose concentrations, raising the possibility that the association between fetuin-A and type 2 diabetes may not be causal.Fetuin-A (also known as α-Heremans-Schmid glycoprotein) is secreted from the liver and reversibly binds the insulin receptor tyrosine kinase in peripheral tissues, thereby inhibiting the insulin-induced intracellular signal cascade and producing peripheral insulin resistance (1–3). Elevated fetuin-A levels have been associated with the risk of incident type 2 diabetes in several human populations (4,5). Recently, we also observed an association between plasma fetuin-A concentrations and risk of type 2 diabetes in a large sample of community-living older adults who participated in the Cardiovascular Health Study (CHS) and were followed for a median of 11 years (6).Thus far, little is known about the potential causal relation between fetuin-A and type 2 diabetes. In the absence of experimental evidence that selective lowering of fetuin-A improves insulin sensitivity and reduces risk of type 2 diabetes, investigations that use genetic variants with strong influence on circulating fetuin-A levels as unconfounded proxies (i.e., Mendelian randomization) may shed light on the potential causal role of fetuin-A in type 2 diabetes.The locus (3q27) where the gene encoding fetuin-A (AHSG) is situated has been identified in human linkage studies of phenotypes such as the metabolic syndrome and type 2 diabetes (7,8). These findings were followed by direct sequencing of gene-encoding regions and the identification of nine highly correlated single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) >5% (9). Case-control studies have suggested that a few of these SNPs (rs1071592, rs4917/rs4918, and rs2248690) are associated with type 2 diabetes and insulin resistance (9,10), but none of these studies had plasma measurements of fetuin-A available to evaluate the potential causal nature of the direct association between fetuin-A and type 2 diabetes. In general, carriers of the minor alleles of promoter variant rs2248690 (T; frequency in Caucasians, ∼26%) and the tightly linked nonsynonymous amino acid substitution variants rs4917 (T; frequency in Caucasians, ∼33%) and rs4918 (G; frequency in Caucasians, ∼34%), have lower levels of circulating fetuin-A compared with carriers of the normal wild-type alleles (11–14).By incorporating information for polymorphisms at the AHSG locus with our previous analysis of plasma fetuin-A in relation to risk of incident type 2 diabetes in the CHS (6), we aimed to address this potential causative association.     

Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program

Objectives. To assess the long‐term effects of chocolate consumption amongst patients with established coronary heart disease. Design. In a population‐based inception cohort study, we followed 1169 non‐diabetic patients hospitalized with a confirmed first acute myocardial infarction (AMI) between 1992 and 1994 in Stockholm County, Sweden, as part of the Stockholm Heart Epidemiology Program. Participants self‐reported usual chocolate consumption over the preceding 12 months with a standardized questionnaire distributed during hospitalization and underwent a health examination 3 months after discharge. Participants were followed for hospitalizations and mortality with national registries for 8 years. Results. Chocolate consumption had a strong inverse association with cardiac mortality. When compared with those never eating chocolate, the multivariable‐adjusted hazard ratios were 0.73 (95% confidence interval, 0.41–1.31), 0.56 (0.32–0.99) and 0.34 (0.17–0.70) for those consuming chocolate less than once per month, up to once per week and twice or more per week respectively. Chocolate consumption generally had an inverse but weak association with total mortality and nonfatal outcomes. In contrast, intake of other sweets was not associated with cardiac or total mortality. Conclusions. Chocolate consumption was associated with lower cardiac mortality in a dose dependent manner in patients free of diabetes surviving their first AMI. Although our findings support increasing evidence that chocolate is a rich source of beneficial bioactive compounds, confirmation of this strong inverse relationship from other observational studies or large‐scale, long‐term, controlled randomized trials is needed.     

Prior alcohol consumption and mortality following acute myocardial infarction

CONTEXT: Studies have found that individuals who consume 1 alcoholic drink every 1 to 2 days have a lower risk of a first acute myocardial infarction (AMI) than abstainers or heavy drinkers, but the effect of prior drinking on mortality after AMI is uncertain. OBJECTIVE: To determine the effect of prior alcohol consumption on long-term mortality among early survivors of AMI. DESIGN AND SETTING: Prospective inception cohort study conducted at 45 US community and tertiary care hospitals between August 1989 and September 1994, with a median follow-up of 3.8 years. PATIENTS: A total of 1913 adults hospitalized with AMI between 1989 and 1994. MAIN OUTCOME MEASURE: All-cause mortality, compared by self-reported average weekly consumption of beer, wine, and liquor during the year prior to AMI. RESULTS: Of the 1913 patients, 896 (47%) abstained from alcohol, 696 (36%) consumed less than 7 alcoholic drinks/wk, and 321 (17%) consumed 7 or more alcoholic drinks/wk. Compared with abstainers, patients who consumed less than 7 drinks/wk had a lower all-cause mortality rate (3.4 vs 6.3 deaths per 100 person-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71) as did those who consumed 7 or more drinks/wk (2.4 vs 6.3 deaths per 100 person-years; HR, 0.38; 95% CI, 0.25-0.55; P<.001 for trend). After adjusting for propensity to drink and other potential confounders, increasing alcohol consumption remained predictive of lower mortality for less than 7 drinks/wk, with an adjusted HR of 0.79 (95% CI, 0.60-1.03), and for 7 or more drinks/wk, with an adjusted HR of 0.68 (95% CI, 0.45-1.05; P =.01 for trend). The association was similar for total and cardiovascular mortality, among both men and women, and among different types of alcoholic beverages. CONCLUSION: Self-reported moderate alcohol consumption in the year prior to AMI is associated with reduced mortality following infarction.