06 May 2014 In General Health




OBJECTIVE: To investigate the associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis (RA). METHODS: We conducted a prospective study consisting of 662 patients with RA who were followed up to 7 years from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study. Smoking and alcohol consumption were assessed through yearly questionnaires. The disease activity and functional status were measured annually by the Disease Activity Score examined in 28 commonly affected joints using C-reactive protein (DAS28-CRP3) and the Modified Health Assessment Questionnaire (MHAQ). Linear mixed models were developed to assess the longitudinal effects of smoking and alcohol consumption on DAS28-CRP3 and MHAQ after adjustment for potential confounders. The HLA-DRB1 shared epitope (HLA-SE) by smoking and alcohol interactions were also evaluated in the analysis. RESULTS: The median followup time of the cohort was 4 years. Current smoking was not associated with DAS28-CRP3 in our study, but was associated with a higher MHAQ than nonsmokers with seropositive RA (p = 0.05). Alcohol consumption showed an approximate J-shaped relationship with MHAQ, with the minima occurring at 5.1-10.0 g/day. Compared to no alcohol use, alcohol consumption of 5.1-10.0 g/day was associated with a significant decrease of MHAQ (p = 0.02). When stratified by HLA-SE, the effect of alcohol consumption appeared to be stronger in HLA-SE-positive RA than HLA-SE-negative RA. CONCLUSION: We found that current smoking was associated with a worse functional status, while moderate alcohol consumption was associated with a better functional status in RA. Replications of these findings in other prospective studies are needed.




06 May 2014 In General Health




OBJECTIVE: To examine the association between alcohol consumption and markers of inflammation in preclinical rheumatoid arthritis (RA). METHODS: We studied 174 incident RA cases with stored blood collected 1-16 years prior to RA symptoms (preclinical RA), from the Nurses' Health Study. Alcohol intake was measured using a detailed food frequency questionnaire administered every 4 years, prior to blood collection. Plasma was tested for biomarkers of inflammation, including high-sensitivity C-reactive protein (hsCRP), anti-cyclic citrullinated peptide (anti-CCP) antibodies, interleukin-6 (IL-6), and soluble tumor necrosis factor receptor II (sTNFRII). Generalized additive models were used to identify structure in the relationship between each biomarker and cumulative average alcohol intake. Then general linear models were used for multivariable adjusted analyses with appropriate polynomial terms of alcohol consumption. RESULTS: After controlling for age at blood collection, smoking, parity and duration of breastfeeding, menopausal status, oral contraceptive use, body mass index, and the time between blood collection and RA onset, we found that the daily alcohol consumption showed a U-shaped association with IL-6 levels in RA patients, prior to symptoms. We also found an inverse relationship between alcohol intake and sTNFRII levels, but no associations with hsCRP or anti-CCP levels. CONCLUSION: These results demonstrate an association between alcohol consumption and markers of inflammation, including IL-6 and sTNFRII, in RA patients, prior to the occurrence of symptoms.




BACKGROUND: Alcohol consumption has multiple biochemical consequences. Only a few of these are useful as diagnostic markers, but many reflect potentially harmful or beneficial effects of alcohol. Average consumption of 2 to 4 drinks per day is associated with lower overall or cardiovascular mortality risk than either lower or higher intake. We have analyzed the dose-response relationships between reported alcohol consumption and 17 biomarkers, with emphasis on intake of up to 3 drinks per day.

METHODS: Biochemical tests were performed on serum from 8,396 study participants (3,750 men and 4,646 women, aged 51 +/- 13 years, range 18 to 93) who had provided information on alcohol consumption in the week preceding blood collection.

RESULTS: Gamma glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, carbohydrate-deficient transferrin, urate, ferritin, and bilirubin showed little or no change with alcohol consumption below 2 to 3 drinks per day, but increased with higher intake. High-density lipoprotein cholesterol and albumin showed increasing results, and insulin showed decreasing results, across the entire range of alcohol use. Biphasic responses, where subjects reporting 1 to 2 drinks per day had lower results than those reporting either more or less alcohol use, occurred for triglycerides, glucose, C-reactive protein, alkaline phosphatase, and butyrylcholinesterase. Increasing alcohol use was associated with decreasing low-density lipoprotein cholesterol (LDL-C) in younger women, but higher LDL-C in older men.

CONCLUSIONS: Some markers show threshold relationships with alcohol, others show continuous ones, and a third group show biphasic or U-shaped relationships. Overall, the biochemical sequelae of low-to-moderate alcohol use are consistent with the epidemiological evidence on morbidity and mortality.

OBJECTIVES: The aim of this study was to assess whether young binge drinkers (BD) have impaired macrovascular and microvascular function and cardiovascular disease risk factors compared with age-matched alcohol abstainers (A).

BACKGROUND: Binge drinking rates are highest on college campuses and among those age 18 to 25 years; however, macrovascular and microvascular endothelial function in young adults with histories of repeated binge drinking (>/= 5 standard drinks in 2 h in men, >/= 4 standard drinks in 2 h in women) has not been investigated.

METHODS: Cardiovascular profiles, brachial artery endothelial-dependent flow-mediated dilation (FMD), and flow-independent nitroglycerin (NTG)-mediated dilation and vasoreactivity of resistance arteries (isolated from gluteal fat biopsies) were evaluated in A and BD. RESULTS: Men and women (18 to 25 years of age; A, n = 17; BD, n = 19) were enrolled. In the BD group, past-month mean number of binge episodes was 6 +/- 1, and the mean duration of binge drinking behavior was 4 +/- 0.6 years. FMD and NTG-mediated dilation were significantly lower in the BD group (FMD: 8.4 +/- 0.7%, p = 0.022; NTG-mediated dilation: 19.6 +/- 2%, p = 0.009) than in the A group (FMD: 11 +/- 0.7%; NTG-mediated dilation: 28.6 +/- 2%). Acetylcholine-induced and sodium nitroprusside-induced dilation in resistance arteries was not significantly different between the A and BD groups. However, endothelin-1-induced constriction was significantly enhanced in the BD group compared with the A group (p = 0.032). No differences between groups were found in blood pressure, lipoproteins, and C-reactive protein.

CONCLUSIONS: Alterations in the macrocirculation and microcirculation may represent early clinical manifestations of cardiovascular risk in otherwise healthy young BD. This study has important clinical implications for screening young adults for a repeated history of binge drinking.

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