Inflammatory Markers and the Risk of Coronary Heart Disease in Men and Women

Department of Oral Health Policy and Epidemiology, Harvard University, Cambridge, Massachusetts, United States
New England Journal of Medicine (Impact Factor: 55.87). 12/2004; 351(25):2599-610. DOI: 10.1056/NEJMoa040967
Source: PubMed


Few studies have simultaneously investigated the role of soluble tumor necrosis factor alpha (TNF-alpha) receptors types 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein, and interleukin-6 as predictors of cardiovascular events. The value of these inflammatory markers as independent predictors remains controversial.
We examined plasma levels of sTNF-R1, sTNF-R2, interleukin-6, and C-reactive protein as markers of risk for coronary heart disease among women participating in the Nurses' Health Study and men participating in the Health Professionals Follow-up Study in nested case-control analyses. Among participants who provided a blood sample and who were free of cardiovascular disease at baseline, 239 women and 265 men had a nonfatal myocardial infarction or fatal coronary heart disease during eight years and six years of follow-up, respectively. Using risk-set sampling, we selected controls in a 2:1 ratio with matching for age, smoking status, and date of blood sampling.
After adjustment for matching factors, high levels of interleukin-6 and C-reactive protein were significantly related to an increased risk of coronary heart disease in both sexes, whereas high levels of soluble TNF-alpha receptors were significant only among women. Further adjustment for lipid and nonlipid factors attenuated all associations; only C-reactive protein levels remained significant. The relative risk among all participants was 1.79 for those with C-reactive protein levels of at least 3.0 mg per liter, as compared with those with levels of less than 1.0 mg per liter (95 percent confidence interval, 1.27 to 2.51; P for trend <0.001). Additional adjustment for the presence or absence of diabetes and hypertension moderately attenuated the relative risk to 1.68 (95 percent confidence interval, 1.18 to 2.38; P for trend = 0.008).
Elevated levels of inflammatory markers, particularly C-reactive protein, indicate an increased risk of coronary heart disease. Although plasma lipid levels were more strongly associated with an increased risk than were inflammatory markers, the level of C-reactive protein remained a significant contributor to the prediction of coronary heart disease.

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Available from: Carolyn Christa Cannuscio
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    • "Although multifactorial in its origin, inflammatory and immunological events are considered to play central roles in initiation and progression of atherosclerotic plaques [1]. Indeed, elevations in soluble markers of inflammation as well as changes in leukocyte subset distribution are frequently reported in patients with CAD [2]–[5]. However, studies on relationships between markers of inflammation and severity of CAD have yielded disparate results [6]–[9]. "
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    ABSTRACT: Methods: Twenty patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and 30 patients with stable angina (SA) underwent CCTA at two occasions, immediately prior to coronary angiography and after three months. Atherosclerotic plaques were classified as calcified, mixed and non-calcified. Blood samples were drawn at both occasions. Leukocyte subsets were analyzed by white blood cell differential counts and flow cytometry. Levels of C-reactive protein (CRP) and interleukin(IL)-6 were measured in plasma. Blood analyses were also performed in 37 healthy controls.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "Whether the sex specific associations of adiponectin on metabolic and atherosclerosis-related events we and others [24,25] observed is due to the interaction between circulating adiponectin and either sex-linked genes and/or sexual hormone effects is not known and deserves further investigations. Sex-specific associations have been reported also for other CV risk factors, including those between elevated plasma levels of sTNF-receptors and coronary heart disease [48], between uric acid and atrial fibrillation [49] and between prolactin and cardiac remodeling [50]. A better understanding of the different role of adiponectin on CV disease across sexes, might be gained by verifying whether adiponectin changes, as obtained by interventional studies, are differently related to CV outcomes in males and females. "
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    ABSTRACT: Background The pathogenesis of cardiovascular (CV) mortality, whose rate is increased in type 2 diabetes, is poorly understood.While high serum adiponectin is associated with increased CV mortality in the general population, no data are available in type 2 diabetes.We here investigated whether this counterintuitive association was observable also in diabetic patients and whether it was sex-specific.Methods Three prospective cohorts were analyzed: 1) Gargano Heart Study (GHS; 359 patients, 58 events/1,934 person-years; py); 2) Health Professional Follow-up Study (HPFS; 833 men, 146 events/10,024 py); 3) Nurses¿ Health Study (NHS; 902 women, 144 events/15,074 py).ResultsIn GHS serum adiponectin predicted CV mortality in men (hazard ratio, HR, and 95% CI per standard deviation, SD, increment¿=¿1.54, 1.19-2.01), but not women (HR¿=¿0.98, 0.48-2.01).Circulating adiponectin predicted CV mortality in men from HPFS (HR¿=¿1.44, 1.21-1.72), but not in women from NHS (HR¿=¿1.08, 0.86-1.35), used as replication samples. In a pooled analysis, HRs were 1.47 (1.27-1.70) in 1,075 men and 1.07 (0.86-1.33) in 1,019 women (p for HRs heterogeneity across sexes¿=¿0.018).Conclusions This is the first report showing that high circulating adiponectin predicts increased CV mortality in men, but not in women with type 2 diabetes. Further studies are necessary to unravel the mechanisms through which adiponectin influences CV mortality in a sex-specific manner.
    Full-text · Article · Sep 2014 · Cardiovascular Diabetology
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    • "In addition, blood hs-CRP levels decreased from baseline to follow-up. hs-CRP, a biomarker of subclinical inflammation, is produced by the liver in response to various inflammatory conditions and is a predictor of cardiovascular disease risk [39,40,41]. These results can be explained by changes in milk and dairy food consumption, which were observed clearly in our study. "
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    ABSTRACT: BACKGROUND/OBJECTIVES The immigrant population has grown considerably in South Korea since the early 1990s due to international marriages. Dietary changes in immigrants are an important issue, because they are related to health and disease patterns. This study was conducted to compare changes in dietary intake between baseline and follow-up periods. SUBJECTS/METHODS Two hundreds thirty three Vietnamese female married immigrants. Baseline data were collected during 2006-2009, and the follow-up data were collected during 2008 and 2010. Food consumption was assessed using a 1-day 24-hour recall. RESULTS The amount of the total food consumed (P < 0.001) including that of cereals (P = 0.004), vegetables (P = 0.003), and fruits (P = 0.002) decreased at follow-up compared to that at baseline, whereas consumption of milk and dairy products increased (P = 0.004). Accordingly, the overall energy and nutrient intake decreased at follow-up, including carbohydrates (P = 0.012), protein (P = 0.021), fiber (P = 0.008), iron (P = 0.009), zinc (P = 0.006), and folate (P = 0.002). Among various anthropometric and biochemical variables, mean skeletal muscle mass decreased (P = 0.012), plasma high density lipoprotein-cholesterol increased, (P = 0.020) and high sensitivity C-reactive protein decreased at follow-up (P < 0.001). CONCLUSIONS A long-term follow-up study is needed to investigate the association between changes in food and nutrient intake and anthropometric and biochemical variables in these Vietnamese female marriage immigrants.
    Full-text · Article · Jun 2014 · Nutrition research and practice
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