Adipocytokines, C-Reactive Protein, and Cardiovascular Disease: A Population-Based Prospective Study

Abstract

BackgroundBeing overweight or obese is associated with a greater risk of coronary heart disease and stroke compared with normal weight. The role of the specific adipose tissue-derived substances, called adipocytokines, in overweight- and obesity-related cardiovascular disease (CVD) is still unclear.ObjectiveTo investigate the associations of three adipose tissue-derived substances: adiponectin, leptin, and interleukin-6 with incident CVD in a longitudinal population-based study, including extensive adjustments for traditional and metabolic risk factors closely associated with overweight and obesity. C-reactive protein (CRP) was used as a proxy for interleukin-6.MethodsProspective population-based study of 6.502 participants, 51.9% women, aged 30–60 years, free of CVD at baseline, with a mean follow-up time of 11.4 years, equivalent to 74,123 person-years of follow-up. As outcome, we defined a composite outcome comprising of the first event of fatal and nonfatal coronary heart disease and fatal and nonfatal stroke.ResultsDuring the follow-up period, 453 composite CV outcomes occurred among participants with complete datasets. In models, including gender, age, smoking status, systolic blood pressure, treatment for hypertension, diabetes, body mass index (BMI), total cholesterol, high-density-lipoprotein cholesterol, homeostasis model assessment of insulin resistance, estimated glomerular filtration rate, adiponectin, leptin, and CRP, neither adiponectin (hazard ratio [HR] with 95% confidence interval [CI]: 0.97 [0.87–1.08] per SD increase, P = 0.60) nor leptin (0.97 [0.85–1.12] per SD increase, P = 0.70) predicted the composite outcome, whereas CRP was significantly associated with the composite outcome (1.19 [1.07–1.35] per SD increase, P = 0.002). Furthermore, in mediation analysis, adjusted for age and sex, CRP decreased the BMI-associated CV risk by 43% (95%CI 29–72).ConclusionsIn this study, neither adiponectin nor leptin were independently associated with CVD, raising questions over their role in CVD. The finding that CRP was significantly associated with an increased risk of CVD and decreased the BMI-associated CVD risk substantially, could imply that interleukin-6-related pathways may play a role in mediating overweight- and obesity-related CVD.

Leptin concentration and risk of coronary heart disease and stroke: A systematic review and meta-analysis

“…A published meta-analysis, comprising eight nested case-control studies with a total of 1980 CVD patients and 11567 participants, indicated a significant association between leptin and pathogenetic risk of CHD and stroke [21]. In contrast, the latest research studies did not find the same association [22–24]. Given the inconsistency of prior results, we performed an updated meta-analysis to investigate the relationship between high leptin concentration and risk of CVD.…”

Increased leptin/adiponectin ratio relates to low-normal thyroid function in metabolic syndrome

“…These findings provide a rationale to hypothesize that the plasma leptin/adiponectin (L/A) ratio is higher in subjects with low-normal thyroid function. Of note, the L/A ratio may represent a preferential marker compared to leptin and adiponectin alone in predicting incident cardiovascular disease [17, 18]. The L/A ratio is also considered to represent a biomarker of adipocyte dysfunction [19].…”

Diabetes mellitus related biomarker: The predictive role of growth-differentiation factor-15

“…The most commonly used inflammatory biomarker in established diabetes is highly selective Creactive protein (hs-CRP), which well correlates with CV complications, poorer metabolic control and severe hypoglycaemia in diabetes, although low sensitivity and specificity of this biomarker was found [11][12][13][14]. Apart from serial testing of hs-CRP, which is time-consuming, other novel pro-inflammatory biomarkers like Growth-Differentiation Factor-15 (GDF-15) have been proposed risk stratify patients with diabetes including type two diabetes mellitus (T2DM) [15].…”