Serum non-esterified fatty acid levels and hip fracture risk: The Cardiovascular Health Study.

Among elderly participants from the Cardiovascular Health Study, we found that non-esterified trans fatty acid levels had a significant prospective association with hip fracture risk. Other non-esterified fatty acid classes were not associated with hip fracture risk. INTRODUCTION: Serum non-esterified fatty acids (NEFAs) are bioactive metabolic intermediates that can be taken up by bone tissue. Their associations with hip fracture risk have not been previously examined. METHODS: Thirty-five individual NEFAs in five classes (saturated [SFA], mono-un-saturated [MUFA], poly-unsaturated n-6 and n-3 [PUFA], and trans-FA) were measured in Cardiovascular Health Study participants (n = 2139, mean age 77.8 years) without known diabetes. The multivariable associations of NEFA levels with hip fracture risk were evaluated in Cox hazards models. RESULTS: We documented 303 incident hip fractures during 11.1 years of follow-up. Among the five NEFA classes, total trans FA levels were positively associated with higher hip fracture risk (HR 1.17 [95% CI, 1.04, 1.31; p = 0.01] per one standard deviation higher level). The SFA lignoceric acid (24:0) was positively associated with higher risk (HR 1.09 [1.04, 1.1]; p < 0.001), while behenic (22:0) and docosatetraenoic (22:4 n6) acids were associated with lower risk (HR 0.76 [0.61, 0.94]; p = 0.01; 0.84 [0.70, 1.00]; p = 0.05, respectively). CONCLUSION: Total plasma trans NEFA levels are related to hip fracture risk, suggesting an unrecognized benefit of their systematic removal from food. Novel associations of individual NEFAs with hip fracture risk require confirmation in other cohort studies.

A safe level of alcohol consumption: the right answer demands the right question.

Alcohol has been produced by humans for nearly ten millennia, but gold-standard evidence by which to judge the health effects of limited alcohol consumption remains elusive, introducing serious difficulty in considering the safety of alcohol consumption. To do so, physicians and policymakers must consider the population, dose and context of alcohol consumption and the end-point, preferably a holistic composite, of interest. The limitations of new research trends, such as mega-cohorts, genetic instrumental variable analysis and modelling studies, must also be viewed against the much larger backdrop of existing evidence. Some existing guidelines, such as the 2015-2020 Dietary Guidelines for Americans, succeed remarkably in this task. Nonetheless, large-scale randomized trials are urgently needed if future generations are to enjoy any greater insight into the health effects of population-wide alcohol consumption than the current one has.

Circulating omega-7 fatty acids are differentially related to metabolic dysfunction and incident type II diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA).

AIM: Determine whether plasma omega-7 vaccenic acid and palmitoleic acid levels are related to homeostasis model of insulin resistance scores and incident type II diabetes, and whether race/ethnicity modifies these associations. METHODS: Plasma phospholipid fatty acids were measured by gas chromatography with flame-ionization detection in Multi-Ethnic Study of Atherosclerosis participants. Linear regression determined associations of vaccenic acid and palmitoleic acid with log-transformed homeostasis model of insulin resistance scores (n=5689), and Cox regression determined associations with incident type II diabetes (n=5413, 660 cases). Race-interactions were tested. RESULTS: Adjusting for typical risk factors, higher levels of plasma vaccenic acid were found to be inversely associated with insulin resistance scores across all four race/ethnicities, and a significant race-interaction was observed between Hispanics and Caucasians (P for interaction=0.03). Vaccenic acid was related to 17%, 32%, and 39% lower risks of incident type II diabetes in Black, Hispanic, and Chinese American participants, respectively. Differences in associations between races were detected (P for interactions<0.05). By contrast, higher levels of plasma palmitoleic acid were related to greater insulin resistance scores in Blacks (P<0.001) and Hispanics (P<0.001); significant race-based differences between associations were detected (P for interactions<0.05). Palmitoleic acid was correspondingly related to a 21% greater risk of incident type II diabetes in Black individuals. CONCLUSIONS: Results suggest that plasma vaccenic acid and palmitoleic acid are markers of metabolic health and dysfunction, respectively. Coupled with previous evidence and the significant race-interactions, our findings have implications for future studies of the race-based differences in omega-7 fatty acids and their regulation in the context of deteriorating metabolic health.

Assessing risk factors of non-fatal outcomes amid a competing risk of mortality: the example of hip fracture.

The Fine-Gray method is often used instead of Cox regression to account for competing risks of death in time-to-event analyses for non-fatal outcomes. A series of examples using well-known risk factors of hip fracture in an older cohort with substantial competing mortality demonstrates that the Fine-Gray approach can yield estimates that implausibly contradict long-established associations, while Cox regression preserves them. Cox regression is generally preferred for risk factor-outcome associations even in the presence of competing risk of death. INTRODUCTION: Factors like age, sex, and race are associated not only with risk of hip fracture but also with mortality. Substantial misunderstanding remains regarding the appropriate statistical approach to account for the competing risk of mortality. METHODS: In the Cardiovascular Health Study, an ongoing cohort study of 5888 older adults, we followed participants for incident hip fracture from their 1992-1993 visit through June 2014. We contrasted the conventional cause-specific Cox analysis, which censors individuals at the time of death, with the Fine-Gray (FG) approach, which extends participant follow-up even after death, to estimate the association of well-established demographic and clinical factors with incident hip fracture. RESULTS: For age, current smoking and sex, Cox and FG methods yielded directionally concordant but quantitatively different strengths of association. For example, the Cox hazard ratio (HR) for a 5-year increment in age was 1.74 (95% CI, 1.61-1.87), while the corresponding FG HR was 1.16 (1.09-1.24). In contrast, the FG approach estimated a stronger association of hip fracture with sex. The two approaches yielded nearly identical results for race. For diabetes and kidney function, the estimates were discordant in direction, and the FG HRs suggested effects that were in the opposite direction of well-understood and widely accepted associations. CONCLUSIONS: Cause-specific Cox models provide appropriate estimates of hazard for non-fatal outcomes like hip fracture even in the presence of competing risk of mortality. The Cox approach estimates hazard in the population of individuals who have not yet had an incident hip fracture and remain alive, which is typically the group of clinical interest. The Fine-Gray method estimates hazard in a hypothetical population that can yield misleading inferences about risk factors in populations of clinical interest.

Biochemical markers of bone turnover and risk of incident hip fracture in older women: the Cardiovascular Health Study.

The relationships of osteocalcin (OC) and C-telopeptide of type I collagen (CTX) with long-term incidence of hip fracture were examined in 1680 post-menopausal women from a population-based study. CTX, but not OC, levels were associated with incident hip fracture in these participants, a relationship characterized by an inverted U-shape. INTRODUCTION: We sought to investigate the relationships of OC, a marker of bone formation, and CTX, a marker of bone resorption, with long-term incidence of hip fracture in older women. METHODS: We included 1680 women from the population-based Cardiovascular Health Study (mean [SD] age 74.5 [5.0] years). The longitudinal association of both markers with incidence of hip fracture was examined using multivariable Cox models. RESULTS: During a median follow-up of 12.3 years, 288 incident hip fractures occurred. Linear spline analysis did not demonstrate an association between OC levels and incident hip fracture. By contrast, increasing levels of CTX up to the middle-upper range were associated with a significantly greater risk of hip fracture (HR = 1.52 per SD increment, 95% CI = 1.10-2.09), while further increases were associated with a marginally non-significant lower risk (HR = 0.80 per SD increment, 95% CI = 0.63-1.01), after full adjustment for potential confounders. In analyses of quartiles, CTX exhibited a similar inverted U-shaped relationship with incident fracture after adjustment, with a significant association observed only for the comparison of quartile 3 to quartile 1 (HR = 1.63, 95% CI = 1.10-2.43). In a subset with available measures, both OC and CTX were inversely associated with bone mineral density of the hip. CONCLUSION: CTX, but not OC, levels were associated with incident hip fracture in post-menopausal women, a relationship characterized by an inverted U-shape. These findings highlight the complex relationship of bone turnover markers with hip fracture risk.

Moderate alcohol consumption and depression - a longitudinal population-based study in Sweden.

BACKGROUND AND AIMS: The interrelationship between alcohol consumption and depression is complex, and the direction of the association is unclear. We investigated whether alcohol consumption influences the risk of depression while accounting for this potential bidirectionality. METHODS: A total of 10 441 individuals participated in the PART study in 1998-2000, 8622 in 2001-2003, and 5228 in 2010. Participants answered questions on their alcohol consumption, symptoms of depression, childhood adversity, and sociodemographic, socioeconomic, psychosocial, and lifestyle factors. A total of 5087 participants provided repeated information on alcohol consumption. We used marginal structural models to analyze the association between alcohol consumption and depression while controlling for previous alcohol consumption and depressive symptoms and other time-varying confounders. RESULTS: Non-drinkers had a higher depression risk than light drinkers (≤7 drinks/week) (risk ratio: 1.7; 95% confidence interval 1.3-2.1). Consumers of seven-fourteen drinks/week had a depression risk similar to that of light drinkers. Hazardous drinking was associated with a higher risk of depression than non-hazardous alcohol consumption (risk ratio: 1.8, 95% confidence interval: 1.4-2.4). CONCLUSION: Light and moderate alcohol consumption and non-hazardous drinking were associated with the lowest risk of subsequent depression after accounting for potential bidirectional effects. Hazardous drinking increased the risk of depression.

The associations of subclinical atherosclerotic cardiovascular disease with hip fracture risk and bone mineral density in elderly adults.

In the absence of clinically recognized cardiovascular disease, increased carotid artery intimal medial thickness was associated with higher hip fracture risk in older adults, despite its association with higher bone mineral density (BMD). Low ankle brachial index and aortic wall thickness were not associated with fracture risk or BMD. INTRODUCTION: Clinically recognized cardiovascular disease (CVD) is associated with osteoporosis and hip fracture risk, but the relationship of subclinical atherosclerosis to bone health is not certain. METHODS: We followed 3385 participants from the Cardiovascular Health Study (mean age 74.7 ± 5.3 years) with a median time to fracture of 12.1 years who underwent baseline carotid artery and aortic wall ultrasound scanning and ankle brachial blood pressure index (ABI) determinations. A subset underwent bone mineral density (BMD) testing. RESULTS: There were 494 hip fractures during follow-up. Among persons without clinical CVD, an average standard-deviation increase in a composite score of maximal common and internal carotid artery intimal medial thickness (cIMT) was associated with increased risk of hip fracture [(HR 1.18 [1.04, 1.35]), even though cIMT was positively associated with BMD. Neither aortic wall thickness nor ABI were associated with hip fracture risk or BMD. Among participants with clinical CVD, cIMT and aortic wall thickness, but not ABI, were associated with increased hip fracture risk. CONCLUSION: Subclinical cIMT is associated with an increased risk of hip fractures despite being associated with increased BMD. This finding suggests that vascular health, even in its early stages, is linked to bone health, by pathways other than BMD.

Alcohol consumption and the risk of incident pulmonary embolism in US women and men.

Essentials The association of moderate alcohol consumption with pulmonary embolism (PE) risk remains unclear. In three large US cohorts, we evaluated the association of alcohol consumption with PE risk. We found no evidence of an association of alcohol consumption amount or frequency with PE risk. Secondary analyses of type and heavy episodic drinking also yielded null findings. SUMMARY: Background Moderate alcohol consumption has been variably associated with hemostatic and fibrinolytic factor levels, but the association between alcohol consumption and the risk of incident pulmonary embolism (PE) remains uncertain. Objective To evaluate alcohol consumption amount and frequency in relation to PE risk. Methods Nurses' Health Study (NHS), NHS II and Health Professionals Follow-Up Study participants free of venous thromboembolism (VTE) at baseline (n = 217 442) reported alcohol consumption by type, quantity and frequency, every 2-4 years. Incident PE cases were identified by self-report and confirmed for participants without cancer. In this cohort study, we used Cox proportional hazards models to estimate multivariable-adjusted hazard ratios (HRs) for PE associated with alcohol consumption amount and, separately, frequency. Secondary analyses evaluated alcohol type and heavy episodic drinking in relation to PE risk, and amount and frequency in relation to medical record-confirmed idiopathic PE and any self-reported VTE risk. Cohort-specific analyses were pooled using random-effects meta-analysis. Results During ≥ 20 years of follow-up, we identified 1939 PE events. We found no strong evidence of an association between PE risk and alcohol consumption amount (pooled HRadj for 5.0-14.9 g day-1 vs. abstention = 0.97 [95% CI, 0.79, 1.20]) or frequency (pooled HRadj for 5-7 drinking days per week vs. abstention = 1.04 [95% CI, 0.88, 1.23]). Secondary analyses of type, heavy episodic drinking, idiopathic PE and VTE also yielded null findings. Conclusions Among three large prospective cohorts of US men and women, we found no evidence of an association between the amount or frequency of alcohol consumption and PE risk.

Fasting and post-glucose load measures of insulin resistance and risk of incident atrial fibrillation: The Cardiovascular Health Study.

BACKGROUND AND AIMS: Existing literature in individuals without diabetes has not demonstrated a relationship between IR and incident AF; however, data are limited and only fasting glucose measures of IR were assessed. We evaluated the relationship of both fasting and post-glucose load IR measures with the development of atrial fibrillation in nondiabetic older adults. METHODS AND RESULTS: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged 65 years or older enrolled in two waves (1989-1990 and 1992-1993), those without prevalent AF or diabetes and with IR measures at baseline were followed for the development of AF, identified by follow-up visit electrocardiograms, hospital discharge diagnosis coding, or Medicare claims data, through 2014. Fasting IR was determined by the homeostatic model of insulin resistance (HOMA-IR) and post-glucose load IR was determined by the Gutt index. Cox proportional hazards models were used to determine the association of IR with risk of AF. Analyses included 3601 participants (41% men) with a mean age of 73 years. Over a median follow-up of 12.3 years, 1443 (40%) developed AF. After multivariate adjustment, neither HOMA-IR nor the Gutt index was associated with risk of developing AF [hazard ratios (95% confidence intervals): 0.96 (0.90, 1.03) for 1-SD increase in HOMA-IR and 1.03 (0.97, 1.10) for 1-SD decrease in the Gutt index]. CONCLUSIONS: We found no evidence of an association between either fasting or post-glucose load IR measures and incident AF.

Brain natriuretic peptide and insulin resistance in older adults.

AIMS: Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established. METHODS: N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance. RESULTS: Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic = 71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP). CONCLUSIONS: In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study.

The association of lean and fat mass with all-cause mortality in older adults: The Cardiovascular Health Study.

BACKGROUND AND AIMS: Understanding contributions of lean and fat tissue to cardiovascular and non-cardiovascular mortality may help clarify areas of prevention in older adults. We aimed to define distributions of lean and fat tissue in older adults and their contributions to cause-specific mortality. METHODS AND RESULTS: A total of 1335 participants of the Cardiovascular Health Study (CHS) who underwent dual-energy x-ray absorptiometry (DEXA) scans were included. We used principal components analysis (PCA) to define two independent sources of variation in DEXA-derived body composition, corresponding to principal components composed of lean ("lean PC") and fat ("fat PC") tissue. We used Cox proportional hazards regression using these PCs to investigate the relationship between body composition with cardiovascular and non-cardiovascular mortality. Mean age was 76.2 ± 4.8 years (56% women) with mean body mass index 27.1 ± 4.4 kg/m2. A greater lean PC was associated with lower all-cause (HR = 0.91, 95% CI 0.84-0.98, P = 0.01) and cardiovascular mortality (HR = 0.84, 95% CI 0.74-0.95, P = 0.005). The lowest quartile of the fat PC (least adiposity) was associated with a greater hazard of all-cause mortality (HR = 1.24, 95% CI 1.04-1.48, P = 0.02) relative to fat PCs between the 25th-75th percentile, but the highest quartile did not have a significantly greater hazard (P = 0.70). CONCLUSION: Greater lean tissue mass is associated with improved cardiovascular and overall mortality in the elderly. The lowest levels of fat tissue mass are linked with adverse prognosis, but the highest levels show no significant mortality protection. Prevention efforts in the elderly frail may be best targeted toward improvements in lean muscle mass.

Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome.

Clonidine, an α2-adrenergic receptor agonist, decreases circulating norepinephrine and epinephrine, attenuating sympathetic activity. Although catechol-O-methyltransferase (COMT) metabolizes catecholamines, main effectors of sympathetic function, COMT genetic variation effects on clonidine treatment are unknown. Chronic fatigue syndrome (CFS) is hypothesized to result in part from dysregulated sympathetic function. A candidate gene analysis of COMT rs4680 effects on clinical outcomes in the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL), a randomized double-blinded clonidine versus placebo trial, was conducted (N=104). Patients homozygous for rs4680 high-activity allele randomized to clonidine took 2500 fewer steps compared with placebo (Pinteraction=0.04). There were no differences between clonidine and placebo among patients with COMT low-activity alleles. Similar gene-drug interactions were observed for sleep (Pinteraction=0.003) and quality of life (Pinteraction=0.018). Detrimental effects of clonidine in the subset of CFS patients homozygous for COMT high-activity allele warrant investigation of potential clonidine-COMT interaction effects in other conditions.

Systemic markers of microvascular disease and bone mineral density in older adults : The cardiovascular health study.

Here we report that abnormal brain white matter and, to a lesser extent, albuminuria are associated with reduced bone mineral density in the hip, spine, and total body in men and women. These findings may explain the increased hip fracture risk reported in some studies in association with microvascular disorders. INTRODUCTION: Markers of microvascular disease have been individually associated with increased risk of osteoporotic fractures in some studies. Here, we examine whether these markers are associated with reduced bone mineral density (BMD) individually and together. METHODS: BMD testing using dual x-ray absorptiometry of the hip, lumbar spine, and total body was performed in 1473 participants from the Cardiovascular Health Study (mean age ~ 78 years): 1215 were assessed for urinary albumin-creatinine ratio, 944 for abnormal white matter disease (AWMD) by brain MRI, and 541 for retinal vascular disease with fundus photographs. Linear regression models were used to evaluate the cross-sectional association of each marker with BMD accounting for potentially confounding factors. RESULTS: AWMD was associated with lower hip, spine, and total body BMD in women (ß -3.08 to -4.53; p < 0.01 for all) and lower hip and total body BMD in men (ß -2.90 to -4.24; p = 0.01-0.03). Albuminuria was associated with lower hip (ß -3.37; p = .05) and total body (ß -3.21; p = .02) BMD in men, but not in women. The associations of AWMD and albuminuria with BMD persisted with mutual adjustment and appeared to be additive to each other. Retinal vascular disease was not associated with BMD in men or women. CONCLUSION: AWMD and, to a lesser extent, albuminuria were independently associated with lower BMD, suggesting that microvascular disease may play a role in the pathogenesis of reduced BMD. These findings need to be confirmed by longitudinal studies.

Weight and weight change and risk of acute myocardial infarction and heart failure - the HUNT Study.

OBJECTIVES: To delineate the association of weight with cardiovascular health throughout adulthood. METHODS: We conducted a population-based prospective cohort study of 26 097 community-dwelling individuals who were followed for 11.4 years with measurements of cardiovascular risk factors and common chronic disorders. Body weight and height were directly measured at baseline in 1995-1997 as they had been 10 and 30 years prior to baseline. From these measurements, we estimated average body mass index (BMI) over time and calculated weight change. RESULTS: The association of average BMI with acute myocardial infarction (AMI) became weaker with adjustment for the most recent BMI measurement, whilst this adjustment had a more limited effect on associations with heart failure (HF) risk. For example, the multi-adjusted hazard ratios for AMI in a comparison of individuals with average BMI until baseline ≥35 kg m(-2) and between 18.5 and 22.4 kg m(-2) decreased from 1.75 [95% confidence interval (CI) 1.04-2.95] to 1.32 (0.73-2.40). The corresponding numbers for HF were 3.12 (1.85-5.27) and 2.95 (1.53-5.71), respectively. The associations between weight change and risk of AMI and HF were U-shaped, with stable weight showing the lowest risk. CONCLUSION: Sustained overweight or obesity over time is associated with increased risk of HF, even after adjustment for the most recent BMI. For AMI risk, the most recent BMI appears to be the most important. Weight change also increases risks for both outcomes beyond the effects of BMI. Our results suggest that a global epidemic of obesity is likely to increase the incidence of HF, even if BMI in middle age can be controlled.

Aspirin use is associated with lower indices of liver fibrosis among adults in the United States.

BACKGROUND: Recent animal studies have shown that platelets directly activate hepatic stellate cells to promote liver fibrosis, whereas anti-platelet agents decrease liver fibrosis. It is unknown whether platelet inhibition by aspirin prevents liver fibrosis in humans. AIM: To examine the association between aspirin use and liver fibrosis among adults with suspected chronic liver disease. METHODS: We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey III. We identified 1856 individuals with suspected chronic liver disease (CLD). The degree of liver fibrosis was determined using four validated fibrosis indices and a composite index. RESULTS: The use of aspirin was associated with a significantly lower composite liver fibrosis index calculated from FIB4, APRI, Forns and NFS [0.24 standard deviation (s.d.) units lower; 95% CI -0.42 to -0.06, P = 0.009]. The association of aspirin with lower fibrosis scores was significantly larger among those with suspected CLD compared to those without (-0.23 vs. -0.03 s.d. units; P interaction = 0.05). The negative association between aspirin use and lower fibrosis index was consistent across all four fibrosis indices (P = 0.002-0.08) in individuals with chronic viral hepatitis, suspected alcoholic liver disease and NASH. In comparison, no negative associations with liver fibrosis were seen with ibuprofen in parallel analyses. CONCLUSIONS: The use of aspirin was associated with significantly lower indices of liver fibrosis among US adults with suspected chronic liver diseases. Aspirin and other anti-platelet drugs warrant further investigation for the prevention and treatment of liver fibrosis.

Bidirectional associations between alcohol consumption and health-related quality of life amongst young and middle-aged women.

BACKGROUND: Evidence from cross-sectional studies has suggested a positive association between moderate alcohol consumption and health-related quality of life but prospective data remain scarce. OBJECTIVES: To examine the bidirectional relationships between alcohol consumption and health-related quality of life using a longitudinal study design. METHODS: A total of 92 448 participants of the Nurses' Health Study II reported their alcohol consumption (in 1991, 1995, 1999 and 2003) and health-related quality of life (in 1993, 1997 and 2001). Using generalized estimating equations, we modelled the physical and mental component summary (PCS and MCS) scores as a function of alcohol consumption 2 years earlier (n = 88 363) and vice versa (n = 84 621). RESULTS: Greater alcohol consumption was associated with better PCS scores 2 years later in a dose-response manner up to ~1 serving daily [mean difference (ß) = 0.67 ± 0.06 PCS units, for moderate versus infrequent drinkers]. After adjustment for previous PCS, a similar but attenuated pattern was observed (ß = 0.33 ± 0.07). Moderate alcohol consumption was not related to MCS, whereas moderate-to-heavy alcohol consumption was associated with lower MCS scores (ß = -0.34 ± 0.15). Higher PCS scores were associated with greater alcohol consumption 2 years later, also after adjustment for previous alcohol consumption (ß = 0.53 ± 0.05 g day(-1) ). MCS was not associated with alcohol consumption 2 years later. CONCLUSION: Amongst young and middle-aged women, moderate alcohol intake was associated with a small improvement in physical health-related quality of life 2 years later and vice versa. Moderate alcohol consumption was not associated with mental health-related quality of life in either direction.

Fibrosis markers, hip fracture risk, and bone density in older adults.

UNLABELLED: We examined whether blood levels of two markers of fibrosis (transforming growth factor beta one (TGF-ß1) and procollagen type III N-terminal propeptide (PIIINP)) are related to hip fracture risk and to bone mineral density (BMD). TGF-ß1 levels were associated with lower hip fracture risk in women and with lower BMD in men. PIIINP levels were not associated with either outcome. INTRODUCTION: TGF-ß1 serves several roles in bone formation and resorption. A consequence of TGF-ß1 activation is the production of PIIINP, a marker of collagen III deposition. Here, we explore whether these two biomarkers are related to incident hip fracture and bone mineral density (BMD) and whether their associations are modified by systemic inflammation, as measured by C-reactive protein (CRP) levels. METHODS: Participants were from the Cardiovascular Health Study (mean age 78 years; mean follow-up 8.3 years). We included 1681 persons with measured levels of TGF-ß1 (149 hip fractures) and 3226 persons with measured levels of PIIINP (310 hip fractures). RESULTS: Among women, higher TGF-ß1 levels were associated with lower hip fracture risk (HR, per doubling, 0.78 [95 % CI 0.61, 0.91]). Among men, TGF-ß1 levels were associated with hip fracture risk in a non-linear manner, but among those with elevated CRP levels, doubling was associated with increased risk of fracture (HR 2.22 [1.20, 4.08]) (p = 0.02, interaction between low and high CRP and TGF-ß1 on fracture risk). TGF-ß1 levels had no significant association with total hip or total body BMD in women but were significantly associated with lower BMD in men. There were no associations of PIIINP levels with hip fracture risk or BMD in men or women. CONCLUSIONS: TGF-ß1 levels appear to be associated with bone-related phenotypes in a sex-specific manner. The reasons for these differences between men and women regarding TGF-ß1 levels and hip fracture risk and bone density require further investigation.

Alcohol consumption is associated with a lower incidence of acute myocardial infarction: results from a large prospective population-based study in Norway.

AIMS: Compelling evidence suggests that light-to-moderate alcohol consumption is associated with a reduced risk of acute myocardial infarction (AMI), but several issues from previous studies remain to be addressed. The aim of this study was to investigate some of these key issues related to the association between alcohol consumption and AMI risk, including the strength and shape of the association in a low-drinking setting, the roles of quantity, frequency and beverage type, the importance of confounding by medical and psychiatric conditions, and the lack of prospective data on previous drinking. METHODS: A population-based prospective cohort study of 58 827 community-dwelling individuals followed for 11.6 years was conducted. We assessed the quantity and frequency of consumption of beer, wine and spirits at baseline in 1995-1997 and the frequency of alcohol intake approximately 10 years earlier. RESULTS: A total of 2966 study participants had an AMI during the follow-up period. Light-to-moderate alcohol consumption was inversely and linearly associated with AMI risk. After adjusting for major cardiovascular disease risk factors, the hazard ratio for a one-drink increment in daily consumption was 0.72 (95% confidence interval 0.62-0.86). Accounting for former drinking or comorbidities had almost no effect on the association. Frequency of alcohol consumption was more strongly associated with lower AMI risk than overall quantity consumed. CONCLUSIONS: Light-to-moderate alcohol consumption was linearly associated with a decreased risk of AMI in a population in which abstaining from alcohol is not socially stigmatized. Our results suggest that frequent alcohol consumption is most cardioprotective and that this association is not driven by misclassification of former drinkers.

Low-fasting triglyceride levels are associated with non-invasive markers of advanced liver fibrosis among adults in the United States.

BACKGROUND: Elevated fasting triglyceride is often associated with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease. On the other hand, as liver disease progresses, patients may develop hepatocellular dysfunction that impairs triglyceride production. AIM: To test the hypothesis that lower fasting triglyceride levels may paradoxically indicate more advanced liver disease. METHODS: A cross-sectional analysis of 11 947 adults aged 20 years or older without chronic viral hepatitis from the National Health and Nutrition Examination Survey 1999-2010 was performed to analyze the relationships between fasting triglyceride levels and five validated non-invasive indices of liver fibrosis, including Fibrosis 4 Score (FIB4), NAFLD Fibrosis Score (NFS), Ast-Platelet Ration Index, AST/ALT ratio and BARD. RESULTS: Low-fasting triglyceride levels were consistently associated with elevated liver fibrosis indices. Individuals in the lowest quintile of triglycerides (TG) had an adjusted odds ratio (OR) of 3.0 (95% CI, 1.7-5.2; P < 0.001) for advanced fibrosis estimated by FIB4 score and OR of 1.8 (95% Cl, 1.2-2.7; P = 0.009) estimated by NFS, compared to individuals in the highest quintile. This association remained highly significant when restricted to individuals with abnormal LFTs from suspected NAFLD. This inverse relationship was continuous, and more pronounced among men and whites (P interaction <0.001 and 0.008 respectively), but not modified by age or body mass index. In addition, fasting TG had a stronger, more direct association with liver fibrosis indices than did albumin or total bilirubin. CONCLUSIONS: Fasting triglyceride levels were inversely associated with liver fibrosis indicators in American adults, especially among white men. Our findings suggest that sequential lipid measurements may serve as a useful disease marker in the management of chronic liver disease patients.