Plasma Levels of Fetuin‐A and Risk of Coronary Heart Disease in US Women: The Nurses' Health Study

Background: Fetuin‐A may be involved in the etiology of coronary heart disease (CHD) through opposing pathways (ie, promoting insulin resistance and inhibiting ectopic calcification). We aimed to explicitly examine whether systemic inflammation, a factor leading to elevated vascular calcification, may modify the association between fetuin‐A and CHD risk. Method and Results During 16 years of follow‐up (1990–2006), we prospectively identified and confirmed 466 incident fatal or nonfatal CHD case in the Nurses' Health Study. For each case, 1 healthy control was selected using risk‐set sampling from 26 245 eligible participants. Cases and controls were matched for age, smoking status, fasting status, and date of blood draw. After multivariate adjustment for lifestyle factors, body mass index, diet, and blood lipids, fetuin‐A levels were not associated with CHD risk in the whole population: odds ratio (OR) (95% CI) comparing extreme quintiles of fetuin‐A was 0.79 (0.44 to 1.40). However, a significant inverse association was observed among participants with higher C‐reactive protein levels (Pinteraction=0.04). The OR (95% CI) comparing highest versus lowest quintiles of fetuin‐A was 0.50 (0.26 to 0.97; Ptrend=0.004) when C‐reactive protein levels were above population median (0.20 mg/dL), whereas among the remainder of the participants, the corresponding OR (95% CI) was 1.09 (0.58 to 2.05; Ptrend=0.75). Conclusions: In this population of US women, fetuin‐A levels were associated with lower CHD risk when C‐reactive protein levels were high, but null association was observed among participants with lower C‐reactive protein levels. This divergent pattern of association needs replication in future studies

Depression and Risk of Sudden Cardiac Death and Coronary Heart Disease in Women Results From the Nurses' Health Study

ObjectivesWe assessed the association between depression and sudden cardiac death (SCD) and cardiac events among individuals without baseline coronary heart disease (CHD).BackgroundDepression is a risk factor for cardiac events and mortality among those with CHD, possibly from arrhythmia.MethodsWe studied depressive symptoms and a proxy variable for clinical depression consisting of severe symptoms and/or antidepressant medication use and their relationship to cardiac events in the Nurses' Health Study. Questionnaires in 1992, 1996, and 2000 assessed symptoms with the Mental Health Index (MHI-5), and antidepressant use was assessed in 1996 and 2000. Primary end points included SCD, fatal CHD, and nonfatal myocardial infarction.ResultsAmong 63,469 women without prior CHD/stroke in 1992, 7.9% had MHI-5 scores <53, previously found to predict clinical depression. Depressive symptoms were associated with CHD events, and the relationship was strongest for fatal CHD, where the association remained significant even after controlling for CHD risk factors (hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.11 to 2.00 for MHI-5 score <53). In models from 1996 onward, our proxy variable for clinical depression was most associated with SCD in multivariable models (HR: 2.33, 95% CI: 1.47 to 3.70), and this risk was primarily due to a specific relationship between antidepressant use and SCD (HR: 3.34, 95% CI: 2.03 to 5.50).ConclusionsIn this cohort of women without baseline CHD, depressive symptoms were associated with fatal CHD, and a measure of clinical depression including antidepressant use was specifically associated with SCD. Although antidepressant use might be a marker of worse depression, its specific association with SCD merits further study

Effect Modification of Long‐Term Air Pollution Exposures and the Risk of Incident Cardiovascular Disease in US Women

Background: Ambient air pollution exposures have been frequently linked to cardiovascular disease (CVD) morbidity and mortality. However, less is known about the populations most susceptible to these adverse effects. Methods and Results: We assessed the associations of long‐term particulate matter (PM) exposures with incident CVD in a nationwide cohort of 114 537 women in the Nurses’ Health Study, and performed analyses to identify subpopulations at the greatest risk. Residential address level time‐varying monthly exposures to PM 2.5, PM 10, and PM 2.5 to 10 microns in diameter were estimated from spatio‐temporal prediction models. In multivariable models, increases in all size fractions of PM were associated with small, but not statistically significant, increased risks of total CVD, coronary heart disease, and stroke. PM‐associated CVD risks were statistically significantly higher among women with diabetes as compared to those without (P‐for‐interaction <0.0001 for PM 10 and PM 2.5 and 0.007 for PM 2.5 to 10). For each 10 μg/m3 increase in 12‐month average PM 2.5, PM 2.5 to 10, and PM 10, the multivariable adjusted hazard ratios were 1.44 (95% CI: 1.23 to 1.68), 1.17 (95% CI: 1.05 to 1.30), and 1.19 (95% CI: 1.10 to 1.28) among women with diabetes. There were also suggestions of higher risks among older (≥70 years) women, the obese, and those living in the Northeast and South. Smoking status and family history did not consistently modify the association between PM and CVD, and risks were most elevated with exposures in the previous 12 months. Conclusions: In this nationwide cohort, women with diabetes were identified as the subpopulation most sensitive to the adverse cardiovascular health effects of PM

Mediterranean diet and telomere length in Nurses’ Health Study: population based cohort study

Objective: To examine whether adherence to the Mediterranean diet was associated with longer telomere length, a biomarker of aging. Design: Population based cohort study. Setting: Nurses’ Health Study, an ongoing prospective cohort study of 121 700 nurses enrolled in 1976; in 1989-90 a subset of 32 825 women provided blood samples. Participants: 4676 disease-free women from nested case-control studies within the Nurses’ Health Study with telomere length measured who also completed food frequency questionnaires. Main outcome measure Association between relative telomere lengths in peripheral blood leukocytes measured by quantitative real time polymerase chain reaction and Alternate Mediterranean Diet score calculated from self reported dietary data. Results: Greater adherence to the Mediterranean diet was associated with longer telomeres after adjustment for potential confounders. Least squares mean telomere length z scores were −0.038 (SE 0.035) for the lowest Mediterranean diet score groups and 0.072 (0.030) for the highest group (P for trend=0.004). Conclusion: In this large study, greater adherence to the Mediterranean diet was associated with longer telomeres. These results further support the benefits of adherence to the Mediterranean diet for promoting health and longevity

Migraine and risk of cardiovascular disease in women: Prospective cohort study

Objective To evaluate the association between migraine and incident cardiovascular disease and cardiovascular mortality in women. Design Prospective cohort study among Nurses’ Health Study II participants, with follow-up from 1989 and through June 2011. Setting Cohort of female nurses in United States. Participants 115 541 women aged 25-42 years at baseline and free of angina and cardiovascular disease. Cumulative follow-up rates were more than 90%. Main outcome measures The primary outcome of the study was major cardiovascular disease, a combined endpoint of myocardial infarction, stroke, or fatal cardiovascular disease. Secondary outcome measures included individual endpoints of myocardial infarction, stroke, angina/coronary revascularization procedures, and cardiovascular mortality. Results 17 531 (15.2%) women reported a physician’s diagnosis of migraine. Over 20 years of follow-up, 1329 major cardiovascular disease events occurred and 223 women died from cardiovascular disease. After adjustment for potential confounding factors, migraine was associated with an increased risk for major cardiovascular disease (hazard ratio 1.50, 95% confidence interval 1.33 to 1.69), myocardial infarction (1.39, 1.18 to 1.64), stroke (1.62, 1.37 to 1.92), and angina/coronary revascularization procedures (1.73, 1.29 to 2.32), compared with women without migraine. Furthermore, migraine was associated with a significantly increased risk for cardiovascular disease mortality (hazard ratio 1.37, 1.02 to 1.83). Associations were similar across subgroups of women, including by age (<50/≥50), smoking status (current/past/never), hypertension (yes/no), postmenopausal hormone therapy (current/not current), and oral contraceptive use (current/not current). Conclusions Results of this large, prospective cohort study in women with more than 20 years of follow-up indicate a consistent link between migraine and cardiovascular disease events, including cardiovascular mortality. Women with migraine should be evaluated for their vascular risk. Future targeted research is warranted to identify preventive strategies to reduce the risk of future cardiovascular disease among patients with migraine

Dietary fiber intake and mortality among survivors of myocardial infarction: prospective cohort study

Objective: To evaluate the associations of dietary fiber after myocardial infarction (MI) and changes in dietary fiber intake from before to after MI with all cause and cardiovascular mortality. Design: Prospective cohort study. Setting: Two large prospective cohort studies of US women and men with repeated dietary measurements: the Nurses’ Health Study and the Health Professionals Follow-Up Study. Participants: 2258 women and 1840 men who were free of cardiovascular disease, stroke, or cancer at enrollment, survived a first MI during follow-up, were free of stroke at the time of initial onset of MI, and provided food frequency questionnaires pre-MI and at least one post-MI. Main outcome measures Associations of dietary fiber post-MI and changes from before to after MI with all cause and cardiovascular mortality using Cox proportional hazards models, adjusting for drug use, medical history, and lifestyle factors. Results: Higher post-MI fiber intake was significantly associated with lower all cause mortality (comparing extreme fifths, pooled hazard ratio 0.75, 95% confidence interval 0.58 to 0.97). Greater intake of cereal fiber was more strongly associated with all cause mortality (pooled hazard ratio 0.73, 0.58 to 0.91) than were other sources of dietary fiber. Increased fiber intake from before to after MI was significantly associated with lower all cause mortality (pooled hazard ratio 0.69, 0.55 to 0.87). Conclusions: In this prospective study of patients who survived MI, a greater intake of dietary fiber after MI, especially cereal fiber, was inversely associated with all cause mortality. In addition, increasing consumption of fiber from before to after MI was significantly associated with lower all cause and cardiovascular mortality

Identifying Metabolomic Profiles of Insulinemic Dietary Patterns

The food-based empirical dietary index for hyperinsulinemia (EDIH) score assesses the insulinemic potential of diet. This cross-sectional study evaluated associations between EDIH scores from food frequency questionnaires with c-peptide concentrations and with 448 metabolites, from fasting plasma samples, in multivariable linear regression analyses. Metabolites were measured with liquid chromatography tandem mass spectroscopy. Using a robust two-stage study design, discovery of metabolite associations was conducted among 1109 Women’s Health Initiative (WHI) Hormone Therapy (HT) trial participants and results replicated in an independent dataset of 810 WHI Observational Study (OS) participants. In both discovery and replication datasets, statistical significance was based on the false-discovery rate adjusted P \u3c 0.05. In the multivariable-adjusted analyses, EDIH was significantly associated with c-peptide concentrations among 919 women (HT & OS) with c-peptide data. On average, c-peptide concentrations were 18% higher (95% CI, 6%, 32%; P-trend \u3c 0.0001) in EDIH quintile 5 compared to quintile 1. Twenty-six metabolites were significantly associated with EDIH in the discovery dataset, and 19 of these were replicated in the validation dataset. Nine metabolites were found to decrease in abundance with increasing EDIH scores and included: C14:0 CE, C16:1 CE, C18:1 CE, C18:3 CE, C20:3 CE, C20:5 CE, C36:1 PS plasmalogen, trigonelline, and eicosapentanoate, whereas the 10 metabolites observed to increase with increasing EDIH scores were: C18:2 SM, C36:3 DAG, C36:4 DAG-A, C51:3 TAG, C52:3 TAG, C52:4, TAG, C54:3 TAG, C54:4 TAG, C54:6 TAG, and C10:2 carnitine. Cholesteryl esters, phospholipids, acylglycerols, and acylcarnitines may constitute circulating metabolites that are associated with insulinemic dietary patterns

Saturated Fats Compared With Unsaturated Fats and Sources of Carbohydrates in Relation to Risk of Coronary Heart Disease A Prospective Cohort Study

AbstractBackgroundThe associations between dietary saturated fats and the risk of coronary heart disease (CHD) remain controversial, but few studies have compared saturated with unsaturated fats and sources of carbohydrates in relation to CHD risk.ObjectivesThis study sought to investigate associations of saturated fats compared with unsaturated fats and different sources of carbohydrates in relation to CHD risk.MethodsWe followed 84,628 women (Nurses’ Health Study, 1980 to 2010), and 42,908 men (Health Professionals Follow-up Study, 1986 to 2010) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years.ResultsDuring 24 to 30 years of follow-up, we documented 7,667 incident cases of CHD. Higher intakes of polyunsaturated fatty acids (PUFAs) and carbohydrates from whole grains were significantly associated with a lower risk of CHD comparing the highest with lowest quintile for PUFAs (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.73 to 0.88; p trend <0.0001) and for carbohydrates from whole grains (HR: 0.90, 95% CI: 0.83 to 0.98; p trend = 0.003). In contrast, carbohydrates from refined starches/added sugars were positively associated with a risk of CHD (HR: 1.10, 95% CI: 1.00 to 1.21; p trend = 0.04). Replacing 5% of energy intake from saturated fats with equivalent energy intake from PUFAs, monounsaturated fatty acids, or carbohydrates from whole grains was associated with a 25%, 15%, and 9% lower risk of CHD, respectively (PUFAs, HR: 0.75, 95% CI: 0.67 to 0.84; p < 0.0001; monounsaturated fatty acids, HR: 0.85, 95% CI: 0.74 to 0.97; p = 0.02; carbohydrates from whole grains, HR: 0.91, 95% CI: 0.85 to 0.98; p = 0.01). Replacing saturated fats with carbohydrates from refined starches/added sugars was not significantly associated with CHD risk (p > 0.10).ConclusionsOur findings indicate that unsaturated fats, especially PUFAs, and/or high-quality carbohydrates can be used to replace saturated fats to reduce CHD risk

Haptoglobin Genotype Is a Consistent Marker of Coronary Heart Disease Risk Among Individuals With Elevated Glycosylated Hemoglobin

ObjectivesThis study sought to investigate into the biologically plausible interaction between the common haptoglobin (Hp) polymorphism rs#72294371 and glycosylated hemoglobin (HbA1c) on risk of coronary heart disease (CHD).BackgroundStudies of the association between the Hp polymorphism and CHD report inconsistent results. Individuals with the Hp2-2 genotype produce Hp proteins with an impaired ability to prevent oxidative injury caused by elevated HbA1c.MethodsHbA1c concentration and Hp genotype were determined for 407 CHD cases matched 1:1 to controls (from the NHS [Nurses' Health Study]) and in a replication cohort of 2,070 individuals who served as the nontreatment group in the ICARE (Prevention of Cardiovascular Complications in Diabetic Patients With Vitamin E Treatment) study, with 29 CHD events during follow-up. Multivariate models were adjusted for lifestyle and CHD risk factors as appropriate. A pooled analysis was conducted of NHS, ICARE, and the 1 previously published analysis (a cardiovascular disease case-control sample from the Strong Heart Study).ResultsIn the NHS, Hp2-2 genotype (39% frequency) was strongly related to CHD risk only among individuals with elevated HbA1c (≥6.5%), an association that was similar in the ICARE trial and the Strong Heart Study. In a pooled analysis, participants with both the Hp2-2 genotype and elevated HbA1c had a relative risk of 7.90 (95% confidence interval: 4.43 to 14.10) for CHD compared with participants with both an Hp1 allele and HbA1c <6.5% (p for interaction = 0.004), whereas the Hp2-2 genotype with HbA1c <6.5% was not associated with risk (relative risk: 1.34 [95% confidence interval: 0.73 to 2.46]).ConclusionsHp genotype was a significant predictor of CHD among individuals with elevated HbA1c