[Show abstract][Hide abstract] ABSTRACT: The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers.
The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 μg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function.
Compared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV1) or forced expiratory flow (FEF25-75). There was no evidence for a smoking by treatment interaction for FEV1, but selenium attenuated rate of decline in FEF25-75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF25-75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E.
Among all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF25-75, a marker of airflow.
Clinicaltrials.gov identifier: NCT00241865 .
Respiratory Research 12/2015; 16(1). DOI:10.1186/s12931-015-0195-5 · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary heart disease (CHD) accounts for one in every six deaths in US individuals. Great advances have been made in identifying important risk factors for CHD, such as hypertension, diabetes mellitus, smoking and hypercholesterolaemia, which have led to major developments in therapy. In particular, statins represent one of the greatest successes in the prevention of CHD. While these standard risk factors are important, an obvious opportunity exists to take advantage of ongoing scientific research to better risk-stratify individuals and to identify new treatment targets. In this Review, we summarize ongoing scientific research in a number of metabolic molecules or features, including lipoproteins, homocysteine, calcium metabolism and glycaemic markers. We evaluate the current state of the research and the strength of evidence supporting each emerging biomarker. We also discuss whether the associations with CHD are strong and consistent enough to improve current risk stratification metrics, and whether these markers enhance our understanding of the underlying biology of CHD and thus point towards new treatment options.
[Show abstract][Hide abstract] ABSTRACT: Background-beta(2)-Microglobulin and cystatin C may have advantages over creatinine in assessing risk associated with kidney function. We therefore investigated whether emerging filtration markers, beta(2)-microglobulin and cystatin C, are prospectively associated with risk of the development of peripheral artery disease (PAD). Methods and Results-We conducted nested case-control studies among women within the Nurses' Health Study (1990-2010) and among men within the Health Professionals Follow-up Study (1994-2008) with the use of archived blood samples collected before PAD diagnosis. During follow-up, symptomatic PAD was confirmed in 144 women and 143 men. Controls were matched 3: 1 based on age, race, smoking status, fasting status, and date of blood sampling. Conditional logistic regression models were used to estimate relative risks (RRs) and were adjusted for plasma creatinine and cardiovascular risk factors. In women, the RRs (95% CI) per 1-SD) increment were 1.16 (0.85 to 1.58) for beta(2)-microglobulin and 0.94 (0.69 to 1.28) for cystatin C. Corresponding RRs in men were 1.50 (1.08 to 2.09) for beta(2)-microglobulin and 1.54 (1.07 to 2.22) for cystatin C. There was no association between creatinine and PAD risk in women, whereas the association in men (RR 1.41, 95% CI 1.10 to 1.81) disappeared after adjustment for either beta(2)-microglobulin or cystatin C. In pooled analyses of men and women, only beta(2)-microglobulin was associated with PAD risk (RR 1.31, 95% CI 1.04 to 1.64). Conclusions-In pooled analyses, beta(2)-microglobulin was associated with an increased risk of symptomatic PAD; a similar association with cystatin C was observed only in men. The findings suggest that beta(2)-microglobulin may capture the atherosclerosis-promoting or atherosclerosis-related elements of kidney dysfunction better than creatinine.
Journal of the American Heart Association 08/2014; 3(4). DOI:10.1161/JAHA.114.000803 · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD.
We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990–2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986–2010). We measured plasma homocysteine in nested matched case–control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990–2010) and 143 PAD cases and 428 controls within the HPFS (1994–2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up.
Higher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08–4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61–2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82–0.98 for each 250 μg increase) but not women (HR 1.01, 95% CI, 0.88–1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women.
Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women.
[Show abstract][Hide abstract] ABSTRACT: The Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets are characterized by higher intake of fruit, vegetables, whole grains, and unsaturated fatty acids. All of these foods and nutrients may affect cholesterol, inflammation, the development of atherosclerosis, and, therefore, risk of cardiac death.
Our objective was to examine the association between the Mediterranean and DASH dietary patterns and risk of sudden cardiac death (SCD) in women.
We used a prospective cohort of 93,122 postmenopausal women enrolled in the Women's Health Initiative study between 1993 and 1998 and followed for an average of 10.5 y. Women completed a food-frequency questionnaire (FFQ) twice during follow-up. We scored their diets according to how closely the reported diet resembled each dietary pattern. SCD was defined as death that occurred within 1 h of symptom onset.
A higher Mediterranean diet score was associated with lower risk of SCD (HR: 0.64; 95% CI: 0.43, 0.94) when women in the highest quintile were compared with women in the lowest quintile after adjustment for age, total energy, race, income, smoking, and physical activity. After adjustment for potential mediators, the association was similar (HR: 0.67; 95% CI: 0.46, 0.99). A higher DASH diet score was not associated with risk of SCD. However, sodium intake, which is a crucial component of the DASH dietary pattern, was not well characterized by the FFQ.
The Mediterranean dietary pattern may be associated with lower risk of SCD in women. This trial was registered at clinicaltrials.gov as NCT00000611.
American Journal of Clinical Nutrition 12/2013; 99(2). DOI:10.3945/ajcn.112.056135 · 6.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Alcohol and caffeine intakes may play a role in the development of sudden cardiac death (SCD) because of their effects on cholesterol, blood pressure, heart rate variability, and inflammation. OBJECTIVE: Our objective was to examine the association between long-term alcohol and caffeine intakes and risk of SCD in women. DESIGN: We examined 93,676 postmenopausal women who participated in the Women's Health Initiative Observational Study. Women were enrolled between 1993 and 1998 and were followed until August 2009. Women completed a food-frequency questionnaire at baseline and again at year 3. We modeled exposure to alcohol 3 ways: by using baseline intake only, a cumulative average of baseline and year 3 intake, and the most recent reported intake (a simple time-varying analysis). RESULTS: Intake of 5-15 g alcohol/d (about one drink) was associated with a nonsignificantly reduced risk of SCD compared with 0.1-5 g/d of baseline intake (HR: 0.64; 95% CI: 0.40, 1.02), of cumulative average intake (HR: 0.69; 95% CI: 0.43, 1.11), and of most recent intake (HR: 0.58; 95% CI: 0.35, 0.96), with adjustment for age, race, income, smoking, body mass index, physical activity, hormone use, and total energy. No association was found between SCD and total caffeine intake (mg/d) or cups of caffeinated coffee, decaffeinated coffee, and caffeinated tea. CONCLUSIONS: Our results suggest that about one drink per day (or 5.1-15 g/d) may be associated with a reduced risk of SCD in this population; however, this association was only statistically significant for a model using the most recent alcohol intake. Total caffeine, regular coffee, decaffeinated coffee, and regular tea intake were not associated with the risk of SCD. This trial was registered at clinicaltrials.gov as NCT00000611.
American Journal of Clinical Nutrition 04/2013; 97(6). DOI:10.3945/ajcn.112.044248 · 6.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: The goal of this study was to examine the prospective association between oxidation-specific biomarkers, primarily oxidized phospholipids (OxPL) on apolipoprotein B-100-containing lipoproteins (OxPL/apoB) and lipoprotein (a) [Lp(a)], and risk of peripheral artery disease (PAD). As secondary analyses, we examined indirect measures of oxidized lipoproteins, including autoantibodies to malondialdehyde-modified low density lipoprotein (MDA-LDL) and apolipoprotein B-100 immune complexes (ApoB-IC). BACKGROUND: Biomarkers to predict the development of PAD are lacking. OxPL circulate in plasma, are transported by Lp(a), and deposit in the vascular wall and induce local inflammation. METHODS: The study population included two parallel nested case-control studies of 143 men within the Health Professionals Follow-up Study (1994-2008) and 144 women within the Nurses' Health Study (1990-2010) with incident confirmed cases of clinically significant PAD, matched 1:3 to controls. RESULTS: Levels of OxPL/apoB were positively associated with risk of PAD in men and women: pooled relative risk (RR) 1.37, 95% CI, 1.19-1.58 for each 1-standard deviation increase after adjusting age, smoking, fasting status, month of blood draw, lipids, body mass index, and other cardiovascular disease risk factors. Lp(a) was similarly associated with risk of PAD (pooled adjusted RR, 1.36; 95% CI, 1.18-1.57 for each 1-standard deviation increase). Autoantibodies to MDA-LDL and ApoB-IC were not consistently associated with risk of PAD. CONCLUSIONS: OxPL/apoB were positively associated with risk of PAD in men and women. The major lipoprotein carrier of OxPL, Lp(a), was also associated with risk of PAD, reinforcing the key role of OxPL in the pathophysiology of atherosclerosis mediated by Lp(a).
Journal of the American College of Cardiology 03/2013; 61(21). DOI:10.1016/j.jacc.2013.02.047 · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: Lower concentrations of adiponectin have been linked to subsequent risk of coronary heart disease in healthy individuals. Whether similar relationships exist for the development of systemic atherosclerosis, such as peripheral artery disease (PAD), is uncertain. We investigated the association between total adiponectin and risk of lower extremity PAD. METHODS AND RESULTS: We performed a prospective, nested case-control study among 18 225 male participants of the Health Professionals Follow-up Study who were free of diagnosed cardiovascular disease at the time of blood draw (1993-1995). During 14 years of follow-up, 143 men developed PAD. Using risk set sampling, controls were selected in a 3:1 ratio and matched on age, smoking status, fasting status, and date of blood draw (n=429). Median (interquartile range) adiponectin concentrations at baseline were lower among cases compared with controls (4.1 [3.2-5.5] versus 5.4 [3.8-7.5] µg/mL; P<0.001). A log-linear inverse association was evident over the full spectrum of adiponectin concentrations with PAD risk after controlling for baseline cardiovascular risk factors using restricted spline conditional logistic regression. Adiponectin was associated with a 42% lower risk of PAD per SD increase in natural log-transformed adiponectin (relative risk, 0.58; 95% confidence interval, 0.45-0.74) after adjustment for cardiovascular risk factors. The relative risk was attenuated (relative risk, 0.68; 95% confidence interval, 0.51-0.92) after further accounting for high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, C-reactive protein, and cystatin C. Additional adjustment for hemoglobin A1c, triglycerides, and γ-glutamyltransferase had little impact on this association (relative risk, 0.68; 95% confidence interval, 0.50-0.92). CONCLUSIONS: Total adiponectin is inversely associated with risk of symptomatic lower extremity PAD in men.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: The aim of this study was to estimate the annual incidence rate of sudden cardiac death (SCD) and to identify risk factors for SCD in post-menopausal women. BACKGROUND: With the aging U.S. population, post-menopausal women now have the greatest population burden of cardiovascular disease including SCD. METHODS: We examined 161,808 women who participated in the Women's Health Initiative clinical trials and observational study. The women were recruited at 40 clinical sites across the United States, enrolled between 1993 and 1998, and followed until August 2009. Our primary endpoint is incident SCD, defined as death occurring within 1 h of symptom onset or within 1 h after the participant was last seen without symptoms and death that occurred in the absence of a potentially lethal non-coronary disease process. RESULTS: Four hundred eighteen women experienced adjudicated SCD. The incidence rate of SCD was 2.4/10,000 women/year (95% confidence interval: 2.2 to 2.7). We identified the following independent risk factors for SCD: older age, African-American race, tobacco use, higher pulse, higher waist-to-hip ratio, elevated white blood cell count, history of heart failure, diabetes, history of myocardial infarction, previous carotid artery disease, and hypertension. Population-attributable fractions were greatest for hypertension, waist-to-hip ratio, and myocardial infarction. CONCLUSIONS: Besides traditional risk factors for coronary heart disease, risk factors for sudden cardiac death in post-menopausal women include African-American race, higher pulse, higher waist-to-hip ratio, elevated white blood cell count, and heart failure. Nearly one-half of women who experienced sudden cardiac death had no previous diagnosis of coronary heart disease.
Journal of the American College of Cardiology 11/2012; 60(25). DOI:10.1016/j.jacc.2012.09.031 · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies have examined the associations of individual clinical risk factors with risk of peripheral artery disease (PAD), but the combined effects of these risk factors are largely unknown.
To estimate the degree to which the 4 conventional cardiovascular risk factors of smoking, hypertension, hypercholesterolemia, and type 2 diabetes are associated with the risk of PAD among men.
Prospective study of 44,985 men in the United States without a history of cardiovascular disease at baseline in 1986; participants in the Health Professionals Follow-up Study were followed up for 25 years until January 2011. The presence of risk factors was updated biennially during follow-up.
Clinically significant PAD defined as limb amputation or revascularization, angiogram reporting vascular obstruction of 50% or greater, ankle-brachial index of less than 0.90, or physician-diagnosed PAD.
During a median follow-up of 24.2 years (interquartile range, 20.8-24.7 years), there were 537 cases of incident PAD. Each risk factor was significantly and independently associated with a higher risk of PAD after adjustment for the other 3 risk factors and confounders. The age-adjusted incidence rates were 9 (95% CI, 6-14) cases/100,000 person-years (n = 19 incident cases) for 0 risk factors, 23 (95% CI, 18-28) cases/100,000 person-years (n = 99 incident cases) for 1 risk factor, 47 (95% CI, 39-56) cases/100,000 person-years (n = 176 incident cases) for 2 risk factors, 92 (95% CI, 76-111) cases/100,000 person-years (n = 180 incident cases) for 3 risk factors, and 186 (95% CI, 141-246) cases/100,000 person-years (n = 63 incident cases) for 4 risk factors. The multivariable-adjusted hazard ratio for each additional risk factor was 2.06 (95% CI, 1.88-2.26). Men without any of the 4 risk factors had a hazard ratio of PAD of 0.23 (95% CI, 0.14-0.36) compared with all other men in the cohort. In 96% of PAD cases (95% CI, 94%-98%), at least 1 of the 4 risk factors was present at the time of PAD diagnosis. The population-attributable risk associated with these 4 risk factors was 75% (95% CI, 64%-87%). The absolute incidence of PAD among men with all 4 risk factors was 3.5/1000 person-years.
Among men in this cohort, smoking, hypertension, hypercholesterolemia, and type 2 diabetes account for the majority of risk associated with development of clinically significant PAD.
JAMA The Journal of the American Medical Association 10/2012; 308(16):1660-7. DOI:10.1001/jama.2012.13415 · 30.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The American Heart Association Task Force released a scientific statement in 2007 for the treatment of hypertension in the prevention of coronary artery disease (CAD). These guidelines recommend more aggressive control of blood pressure (BP) among those at high risk for CAD: individuals with diabetes mellitus, chronic kidney disease, cardiovascular disease, congestive heart failure, or a 10-year Framingham risk score ≥10%. These individuals are advised to maintain a BP <130/80 mm Hg. We estimated the burden of uncontrolled BP among those at an increased risk of CAD using the updated task force guidelines. We used a cross-sectional analysis of National Health and Nutrition Examination Survey 2005-2008 participants. Participants were 24 989 adults aged 18 to 85 years. Using the old definition of hypertension (>140/90 mm Hg), 98 million (21%) Americans have hypertension. Using the updated guidelines, an additional 52 million (11%) American adults now have elevated BP requiring treatment, for a total of 150 million adults (32%). Adults with diabetes mellitus have the greatest population burden of uncontrolled BP (50.6 million), followed by adults with chronic kidney disease (43.7 million) and cardiovascular disease (43.3 million). Although individuals at a higher risk for CAD are more likely to be aware of their hypertension and to be taking antihypertension medication, they are less likely to have their BP under control. Additional efforts are needed in the treatment of elevated BP, especially among individuals with an increased risk of CAD.
[Show abstract][Hide abstract] ABSTRACT: A family history of later-onset breast cancer (FHLBC) may suggest multi-factorial inheritance of breast cancer risk, including unhealthy lifestyle behaviors that may be shared within families. We assessed whether adherence to lifestyle behaviors recommended for breast cancer prevention--including maintaining a healthful body weight, being physically active and limiting alcohol intake--modifies breast cancer risk attributed to FHLBC in postmenopausal women.
Breast cancer outcomes through August 2003 were analyzed in relationship to lifestyle and risk factors collected by questionnaire during enrollment (between 1993 and 1998) of 85,644 postmenopausal women into the Women's Health Initiative Observational Study.
During a mean follow-up of 5.4 years, 1997 women were diagnosed with invasive breast cancer. The rate of invasive breast cancer among women with an FHLBC who participated in all three behaviors was 5.94 per 1,000 woman-years, compared with 6.97 per 1,000 woman-years among women who participated in none of the behaviors. The rate among women with no FHLBC who participated in all three behavioral conditions was 3.51 per 1,000 woman-years compared to 4.67 per 1,000 woman-years for those who participated in none. We did not observe a clinically important departure from additive effects (Interaction Contrast: 0.00014; 95% CI: -0.00359, 0.00388).
Participating in breast healthy behaviours was beneficial to postmenopausal women and the degree of this benefit was the same for women with and without an FHLBC.
Breast cancer research: BCR 10/2010; 12(5):R82. DOI:10.1186/bcr2727 · 5.88 Impact Factor