Plasma Phospholipid Fatty Acid Concentration and Incident Coronary Heart Disease in Men and Women: The EPIC-Norfolk Prospective Study

Background

The lack of association found in several cohort studies between dietary saturated fat and coronary heart disease (CHD) risk has renewed debate over the link between dietary fats and CHD.

Methods and Findings

We assessed the relationship between plasma phospholipid fatty acid (PFA) concentration and incident CHD using a nested case control design within a prospective study (EPIC-Norfolk) of 25,639 individuals aged 40–79 years examined in 1993–1997 and followed up to 2009. Plasma PFA concentrations were measured by gas chromatography in baseline samples retrieved from frozen storage. In 2,424 men and women with incident CHD compared with 4,930 controls alive and free of cardiovascular disease, mean follow-up 13 years, saturated PFA (14:0, 16:0,18:0) plasma concentrations were significantly associated with increased CHD risk (odds ratio [OR] 1.75, 95% CI 1.27–2.41, p<0.0001), in top compared to bottom quartiles (Q), and omega-6 polyunsaturated PFA concentrations were inversely related (OR 0.77, 0.60–0.99, p<0.05) after adjusting for age, sex, body mass index, blood pressure, smoking, alcohol intake, plasma vitamin C, social class, education, and other PFAs. Monounsaturated PFA, omega-3 PFA, and trans PFA concentrations were not significantly associated with CHD. Odd chain PFA (15:0, 17:0) concentrations were significantly inversely associated with CHD (OR 0.73, 0.59–0.91, p<0.001, Q4 versus Q1). Within families of saturated PFA or polyunsaturated PFA, significantly heterogeneous relationships with CHD were observed for individual fatty acids.

Conclusions

In this study, plasma concentrations of even chain saturated PFA were found to be positively and omega-6 polyunsaturated PFA inversely related to subsequent coronary heart disease risk. These findings are consistent with accumulating evidence suggesting a protective role of omega-6 fats substituting for saturated fats for CHD prevention. Please see later in the article for the Editors'' Summary     

Multilocus Heterozygosity and Coronary Heart Disease: Nested Case-Control Studies in Men and Women

BackgroundGeneralized allelic heterozygosity has been proposed to improve reproductive fitness and has been associated with higher blood pressure, but its association with chronic disease is not well characterized.MethodsUsing the Affymetrix Genome-Wide Human 6.0 array, we performed whole genome scans in parallel case-control studies of coronary heart disease (CHD) nested in the Health Professionals Follow-up Study and Nurses’ Health Study. We examined ~700,000 single nucleotide polymorphisms (SNPs) in 435 men with incident CHD and 878 matched controls and 435 women with incident CHD with 931 matched controls. We examined the relationship of genome-wide heterozygosity with risk of incident of CHD and with baseline levels of cardiovascular risk factors.ResultsIn both cohorts, approximately 227650 (SD 2000) SNPs were heterozygous. The number of heterozygous SNPs was not related to risk of CHD in either men or women (adjusted odds ratios per 2000 heterozygous SNPs 1.01 [95% confidence interval, 0.91-1.13] in women and 0.94 [0.84-1.06] in men). We also found no consistent associations of genome-wide heterozygosity with levels of lipids, inflammatory markers, adhesion molecules, homocysteine, adiponectin, or body-mass index.ConclusionsIn these parallel nested case-control studies, we found no relationship of multilocus heterozygosity with risk of CHD or its major risk factors. Studies in other populations are needed to rule out associations with lower levels of heterozygosity.     

Prediction of Risk Factors for Coronary Heart Disease Using Framingham Risk Score in Korean Men

Background

Currently, there is sparse data available on the relationship between coronary heart disease (CHD) and its risk factors estimated by the Framingham Risk Score (FRS) in Korea. This is particularly true when looking at risk factors of CHD associated with the FRS after adjustment for other covariates especially in healthy subjects.

Methodology/Principal Findings

We conducted a prospective cohort study to examine the association between the risk factors of CHD and the risk for CHD estimated by FRS in 15,239 men in 2005 and 2010. The FRS is based on six coronary risk factors: gender, age, total cholesterol, high-density lipoprotein (HDL)-cholesterol, systolic blood pressure (BP), and smoking habit. Multiple linear regression analysis was used to analyze the relationships between the FRS and risk factors for CHD. This study reported that apolipoproetein B (apoB), apoA-I, apoB/apoA-I, alcohol intake, log-transformed TG, log-transformed hsCRP, LDL-cholesterol, hypertension, diabetes, regular exercise, and BMI were significantly associated with the FRS. Above all, the partial R-square of apoB was 14.77%, which was overwhelmingly bigger than that of other variables in model V. This indicated that apoB accounted for 14.77% of the variance in FRS.

Conclusion/Significance

In this study, apoB was found to be the most important determinant for the future development of CHD during a 5-year follow-up in healthy Korean men.     

Optimal Body Weight for the Prevention of Coronary Heart Disease in Normal‐weight Physically Active Men

Although 36% of US men are normal weight (BMI <25 kg/m²), the health benefits of greater leanness in normal‐weight individuals are seldom acknowledged. To assess the optimal body weight with respect to minimizing coronary heart disease (CHD) risk, we applied Cox proportional hazard analyses of 20,525 nonsmoking, nondiabetic, normal‐weight men followed prospectively for 7.7 years, including 20,301 who provided follow‐up questionnaires. Two‐hundred and forty two men reported coronary artery bypass graph (CABG) or percutaneous transluminal coronary angioplasty (PTCA) and 82 reported physician‐diagnosed incident myocardial infarction (267 total). The National Death Index identified 40 additional ischemic heart disease deaths. In these normal‐weight men, each kg/m² decrement in baseline BMI was associated with 11.2% lower risk for total CHD (P = 0.005), 13.2% lower risk for nonfatal CHD (P = 0.002), 19.0% lower risk for nonfatal myocardial infarction (P = 0.01), and 12.2% lower risk for PTCA or CABG (P = 0.007). Compared to men with BMI between 22.5 and 25 kg/m², those <22.5 kg/m² had 24.1% lower total CHD risk (P = 0.01), 27.9% lower nonfatal CHD risk (P = 0.01), 37.8% lower nonfatal myocardial infarction risk (P = 0.05), and 27.8% lower PTCA or CABG risk (P = 0.02). In nonabdominally obese men (waist circumference <102 cm), CHD risk declined linearly with declining waist circumference. CHD risk was unrelated to change in waist circumference between 18 years old and baseline except as it contributed to baseline circumference. These results suggest that the optimal BMI for minimizing CHD risk lies somewhere <22.5 kg/m², as suggested from our previous analyses of incident diabetes, hypertension, and hypercholesterolemia in these men.     

Effects of Obesity Phenotype on Coronary Heart Disease Risk Factors in Response to Weight Loss

Objective: To determine whether there is a difference in risk‐factor improvement for coronary heart disease (CHD) between the intra‐abdominal fat (IF) and subcutaneous fat (SF) obesity phenotypes after weight loss. Research Methods and Procedures: Subjects included 55 mildly obese women (body mass index, 25 to 36 kg/m²; age range, 34 to 63 years) who had at least two of three CHD risk factors [systolic blood pressure (SBP), >140 mm Hg; total cholesterol (TC), >220 mg/dL; fasting plasma glucose, >110 mg/dL). Using computed tomography, IF obesity was classified as ≥110 cm² of the IF area measured; subjects with <110 cm² were classified as having SF obesity. The IF and SF obesity groups were divided into diet‐only and diet‐plus‐exercise groups. Assays and measurements were performed before and after a 14‐week (98‐day) intervention. Results: Weight was reduced by 7 to 10 kg in each group. The IF and SF areas, SBP, diastolic blood pressure, TC, and low‐density lipoprotein‐cholesterol were significantly reduced in all groups (p < 0.01). Reduction in IF area was greater in IF obesity than in SF obesity, whereas no differences were observed in the improvement of CHD risk factors. Sample sizes needed for observing a significant difference for SBP, TC, triglycerides, and fasting plasma glucose were greater than the number of subjects in this study. Discussion: Our results suggest that the influence of the obesity phenotype on improving CHD risk factors is not apparent. A larger study is needed to prove the validity of this finding.     

Self-Reported Substantial 1-Year Weight Change Among Men and Women in the United States

Population-based data have not been readily available on relatively short-term changes in weight. Therefore, we sought to determine the nature of self-reported substantial (> 10%) weight change over one year in a representative sample of the US population which participated in the 1989 National Health Interview Survey (NHIS). Across all ages, a larger proportion of women than men reported both weight loss as well as weight gain of any amount (18.9% vs. 16.1% for weight loss and 20.0% vs. 16.1% for weight gain). In sex-specific logistic regression analyses, significant risk factors common to both sexes for substantial weight loss included divorced/separated marital status, smoking, increased number of blood pressure checks, increased BMI (body mass index) and increased number of bed days. Black race reduced the risk of weight loss for both men and women. Sex-specific risk factors for weight loss in men only were widowhood or never married marital status, while increasing age was a protective factor in women only. Concerning weight gain > 10% over the past year, increased number of blood pressure checks and having one or more diabetic parents were significant risk factors among both men and women; while never being married, increased age, BMI, and education exerted a protective effect in both sexes. For women only, risk factors for weight gain included black race, increased number of contacts with a health professional, and being unemployed. Intention to lose weight was associated with both weight gain and weight loss in both sexes, although it did not serve as a confounder in any of these relationships. A greater likelihood of substantial weight loss among women relative to men was diminished for persons with higher BMI, higher number of blood pressure checks, being widowed, divorced or separated, and intention to lose weight. A greater likelihood of substantial weight gain among women relative to men was diminished for persons with low BMI. The results of this cross-sectional study of weight change, involving a one-year follow-up period, generally correspond with the results obtained by longitudinal studies involving a longer follow-up.     

Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease

Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10⁻⁷ for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.     

Assessment of Global Coronary Heart Disease Risk in Overweight and Obese African‐American Women

Objective : To examine, with the use of national guidelines, coronary heart disease (CHD) risk with increasing BMI for primary prevention in urban African‐American women. Research Methods and Procedures : Participants were recruited for CHD risk factor screening from 20 churches as part of a larger study of nutrition and fitness (Project Joy). All participants had a demographic, smoking and medical history assessment, and the following measurements were taken: weight, height, waist circumference, blood pressure, lipid levels, and glucose. Three methods of defining risk, the Framingham Point Scoring System, a count of risk factors, and the presence of the multiple metabolic syndrome, based on the National Cholesterol Education Program Adult Treatment Panel III Report and BMI classes established by the Clinical Guidelines, were used. Results : A total of 396 women were eligible. Participants were 40 to 80 years of age and had marked excess prevalence of overweight and obesity (84%); 55% were obese. There was a linear increase in risk factors as BMI increased. Lipids did not differ significantly among BMI classifications. Seventeen percent of women had multiple metabolic syndrome. Eight percent and 16% of women in the normal and overweight BMI classes, respectively, had two or more modifiable risk factors. There was no difference in number of modifiable risk factors among the obese classes. The Framingham Point Scoring System assigned a <10% risk of a hard CHD event in 10 years to 97% of the women. Discussion : National risk assessment guidelines for primary prevention of CHD may not be adequate for overweight and obese urban African‐American women and require further study.     

Weight Control Behaviors Among Adult Men and Women: Cause for Concern?

NEUMARK-SZTAINER, DIANNE, NANCY E. SHERWOOD, SIMONE A. FRENCH, AND ROBERT W. JEFFERY. Weight control behaviors among adult men and women: cause for concern? Obes Res. Objectives To examine gender differences in weight control behaviors; their duration and the consistency of their use over a 3-year period; and variations of these behaviors by body mass index (BMI). Research Methods and Procedures The study population included 714 women and 229 men participating in a community-based weight gain prevention program who completed surveys about their weight control behaviors annually for 3 years. General dieting behaviors (e.g., current, regular, and past dieting), dietary restraint (using Restrained Eating subscale of the Three-Factor Eating Questionnaire), and specific weight control practices (e.g., increasing exercise, skipping meals, and taking laxatives) were assessed. Results Women were more likely than men to report weight control behaviors, with particularly strong associations found between gender and “history of dieting” (odds ratio = 8.1) and “participation in an organized weight loss program” (odds ratio = 11.7). Among both genders, exercise was the most frequently reported specific weight loss practice (66% of women and 53% of men), followed by decreasing fat intake (62% of women and 48% of men). The use of at least one unhealthy weight control behavior over the past year was reported by 22% of the women and 17% of the men. Gender differences were not found for duration of use of most of the specific weight control practices over the past year, or for consistency of general dieting behaviors and dietary restraint over time. Although both gender and BMI were strongly associated with dieting behaviors, interactions between gender and BMI on prevalence rates of dieting were not significant. Discussion Although weight control behaviors were more prevalent among women than men, in general, large gender differences were not found in the types of behaviors used and the duration and consistency of their use. The high percentages of adults using healthy methods of weight control was encouraging. However, there is still cause for concern, in that unhealthy weight control practices were also reported by a significant percentage of the population.     

Meta-Analysis of RAGE Gene Polymorphism and Coronary Heart Disease Risk

Background

Recent data from human and animal studies have shown an upregulated expression of advanced glycosylation end product–specific receptor (RAGE) in human atherosclerotic plaques 1 and in retina, messangial, and aortic vessels, suggesting an important role of RAGE in the pathogenesis of atherothrombotic diseases. In the past few years, the relationship between RAGE polymorphisms (−429T/C, −374T/A, and G82S) and coronary heart disease (CHD) has been reported in various ethnic groups; however, these studies have yielded contradictory results.

Methods

PubMed, ISI web of science, EMBASE and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between RAGE polymorphisms and susceptibility to CHD. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

A total of 17 studies including 4343 patients and 5402 controls were involved in this meta-analysis. Overall, no significant results were observed for −429T/C (OR  = 1.01, 95% CI: 0.92–1.12, P  = 0.78), −374T/A (OR  = 1.11, 95% CI: 0.98–1.26, P  = 0.09) and G82S (OR  = 1.12, 95% CI: 0.86–1.45, P  = 0.41) polymorphism. In the stratified analyses according to ethnicity, sample size, CHD endpoint and Hardy-Weinberg status, no evidence of any gene-disease association was obtained.

Conclusions

This meta-analysis demonstrates that there is no association between the RAGE −429T/C, −374T/A and G82S polymorphisms and CHD.     

Association of Plasma Resistin Levels with Coronary Heart Disease in Women

Objective: To examine the association between plasma resistin levels and the presence of coronary heart disease (CHD) in women. Research Methods and Procedures: Plasma resistin levels were measured in a case‐control study including 185 women with angiographically confirmed CHD and 227 population‐based female controls from the Coronary Risk Factors for Atherosclerosis in Women (CORA) study. Results: After adjustment for age, smoking, family history of myocardial infarction, retirement, education, physical activity, menopausal status, hormone replacement use, BMI, hypertension, diabetes, and dyslipidemia, the odds ratio for CHD for women in the highest compared with lowest quintile of plasma resistin levels was 3.19 (95% confidence interval, 1.44 to 7.10; p log trend, 0.001). After additional adjustment for plasma C‐reactive protein levels, this association was substantially attenuated and no longer significant (odds ratio, 1.80; 95% confidence interval, 0.69 ti 4.69; p trend = 0.23). Discussion: These results suggest that plasma resistin levels are significantly associated with the presence of CHD in women; however, this association can largely be explained by concomitant inflammatory processes. Further studies are needed to determine the causal role of resistin in the development of CHD in humans.     

冠心病患者TNF-a 水平及其基因多态性的研究

为了研究中国汉族人群中血清肿瘤坏死因子-a（TNF-a）水平及其-857、-863位点基因多态性与冠心病之间的相关性, 采用双抗体夹心ELISA法检测血清TNF-a水平,同时应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测TNF-a基因多态性。 冠心病组血清TNF-a水平显著高于对照组（P<0.05）,-863 位点基因多态性在两组间分布有显著差异(P<0.05),-857位点分布无差异。血清TNF-a水平显著升高提示炎性反应在冠心病病程中有重要作用,TNF-a的水平受其基因多态性的影响。     

Clinical Utility of a Coronary Heart Disease Risk Prediction Gene Score in UK Healthy Middle Aged Men and in the Pakistani Population

BackgroundNumerous risk prediction algorithms based on conventional risk factors for Coronary Heart Disease (CHD) are available but provide only modest discrimination. The inclusion of genetic information may improve clinical utility.MethodsWe tested the use of two gene scores (GS) in the prospective second Northwick Park Heart Study (NPHSII) of 2775 healthy UK men (284 cases), and Pakistani case-control studies from Islamabad/Rawalpindi (321 cases/228 controls) and Lahore (414 cases/219 controls). The 19-SNP GS included SNPs in loci identified by GWAS and candidate gene studies, while the 13-SNP GS only included SNPs in loci identified by the CARDIoGRAMplusC4D consortium.ResultsIn NPHSII, the mean of both gene scores was higher in those who went on to develop CHD over 13.5 years of follow-up (19-SNP p=0.01, 13-SNP p=7x10^-3). In combination with the Framingham algorithm the GSs appeared to show improvement in discrimination (increase in area under the ROC curve, 19-SNP p=0.48, 13-SNP p=0.82) and risk classification (net reclassification improvement (NRI), 19-SNP p=0.28, 13-SNP p=0.42) compared to the Framingham algorithm alone, but these were not statistically significant. When considering only individuals who moved up a risk category with inclusion of the GS, the improvement in risk classification was statistically significant (19-SNP p=0.01, 13-SNP p=0.04). In the Pakistani samples, risk allele frequencies were significantly lower compared to NPHSII for 13/19 SNPs. In the Islamabad study, the mean gene score was higher in cases than controls only for the 13-SNP GS (2.24 v 2.34, p=0.04). There was no association with CHD and either score in the Lahore study.ConclusionThe performance of both GSs showed potential clinical utility in European men but much less utility in subjects from Pakistan, suggesting that a different set of risk loci or SNPs may be required for risk prediction in the South Asian population.     

同型半胱氨酸与冠心病

随着社会的进步以及人类生活水平的提高,冠心痛的发病率也逐年提高,目前已经成为全球死亡率最高的疾病之一,同时医学水平的不断发展也使得人们对冠心病有了更进一步的研究.近年来同型半胱氨酸越来越受到人们的关注,众多研究表明,高同型半胱氨酸血症是冠心痛的独立危险因子,可以影响冠心病的严重程度及预后.但是迄今为止,同型半胱氨酸在冠心病发病中的确切机制尚不完全明确,认为主要与血管内皮损伤、血管平滑肌细胞增殖凋亡、破坏凝血纤溶系统、影响糖、蛋白质、脂质代谢等方面有关.针对高同型半胱氨酸血症的治疗,对于改善冠心病患者的预后有一定疗效.因此,本文就同型半胱氨酸冠心痛的关系作一综述,从而为临床更好的防治冠心痛提供相关的资料.     

Hematocrit and Coronary Heart Disease

Hematocrit values of patients with acute myocardial infarction have been reported by some workers to be higher than those found in controls; this has been denied by others. In these reported studies important postural, postprandial, age and stress effects have not been considered. In the present investigation hematocrits of healthy and coronary subjects were determined under the same “standard basal” conditions, in the morning hours, fasting or after a light breakfast, and in sitting position; patients studied had no acute illness or distress. A mean hematocrit of 49.1 ± 2.4% was observed in 66 men with chronic coronary disease and of 46.8 ± 3.2% in 68 healthy controls of the same age and sex, the difference being highly significant. The increased hematocrit and plasma viscosity in coronary patients creates significantly higher whole blood viscosity than that observed in healthy controls. This hemodynamic factor may be responsible for the development of clinical symptoms of coronary heart disease and possibly of the basic vascular disease itself.