C-Reactive Protein, the Metabolic Syndrome, and Prediction of Cardiovascular Events in the Framingham Offspring Study

Abstract

Background-Inflammation (assessed by C-reactive protein [CRP]) and the metabolic syndrome (MetS) are associated with cardiovascular disease (CVD), but population-based data are limited. Methods and Results-We assessed the cross-sectional relations of CRP to the MetS (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition) in 3037 subjects (1681 women; mean age, 54 years) and the utility of CRP and the MetS to predict new CVD events (nϭ189) over 7 years. MetS (Ն3 of 5 traits) was present in 24% of subjects; mean age-adjusted CRP levels for those with 0, 1, 2, 3, 4, or 5 MetS traits were 2.2, 3.5, 4.2, 6.0, or 6.6 mg/L, respectively (P trend Ͻ0.0001).In persons with MetS, age-adjusted CRP levels were higher in women than men (7.8 versus 4.6 mg/L; PϽ0.0001). MetS and baseline CRP were individually related to CVD events (for MetS: age-sex-adjusted hazard ratio [HR], 2.1; 95% CI, 1.5 to 2.8; for highest versus lowest CRP quartile: HR, 2.2; 95% CI, 1.4 to 3.5). Greater risk of CVD persisted for MetS and CRP even after adjustment in a model including age, sex, MetS (HR, 1.8; 95% CI, 1.4 to 2.5), and CRP (HR, 1.9; 95% CI, 1.2 to 2.9). The c-statistic associated with the age-and sex-adjusted model including CRP was 0.72; including MetS, 0.74; and including CRP and MetS, 0.74. Conclusions-Elevated CRP levels are related to insulin resistance and the presence of the MetS, especially in women.Although discrimination of subjects at risk of CVD events using both MetS and CRP is not better than using either phenotype alone, both CRP and MetS are independent predictors of new CVD events.

C‐Reactive Protein Identifies Low‐Risk Metabolically Healthy Obese Persons: The European Prospective Investigation of Cancer–Norfolk Prospective Population Study

“…CRP levels and HRs for CHD were similar to those observed in previous publications 3. The prevalence of metabolic risk criteria was in agreement with other large observational cohort studies, whereas the prevalence of the metabolically healthy but obese phenotype was somewhat higher in our population compared with previous studies,19 probably because we defined abdominal obesity by waist circumference, whereas other studies used other measures to determine obesity (eg, body mass index) 12. It must be noted that in view of the subgroups used in our analyses, differences in our population did not always reach our predefined significance level.…”

“…Ridker et al previously reported an age‐adjusted HR of 2.3 (95% CI 1.6–3.3) for women with the MS if CRP levels <3 mg/L were present in contrast to the HR of 4.0 (95% CI 3.0–5.4) if CRP levels >3 mg/L were present 9. Rutter et al similarly observed that CRP independently predicted CHD above the presence of the MS in the Framingham prospective cohort study 12. We found similar associations for abdominally obese participants with elevated CRP levels showing an increased risk for CHD compared with abdominally obese participants with low CRP levels.…”

“…Experimental and observational evidence suggests that inflammation may play a central role in the pathogenesis of cardiovascular disease 8. CRP is associated with all parameters of the MS9 and has been acknowledged to be an independent but not causal2, 10 risk factor for incident CHD and to add prognostic value for CHD risk on top of the MS criteria 3, 9, 11, 12, 13, 14…”

Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus

“…132 However, the estimated RR for menstrual irregularity was no greater than 1.5 (95% CI, 1.10-2.04 for overweight, very irregular women), which is comparable to the HRs of 1.65 (95% CI, 1.10-2.47) to 2.1 (95% CI, 1.5-2.8) for cardiovascular events from the metabolic syndrome alone in other cohorts. 133,134 Because menstrual irregularity increases the risk for insulin resistance and DM, 135 risk associated with menstrual irregularity may not be attributable to PCOS per se but to insulin resistance, the metabolic syndrome, or obesity. Other PCOS criteria of androgen excess and polycystic ovaries have been associated with an increased risk for coronary occlusion or cardiovascular events in postmenopausal women.…”

The Role of Noninvasive Imaging for Detection High Risk Patients with Subclinical Atherosclerosis

“…The carotid-femoral PWV were analyzed in healthy subjects, hypertensive subjects too and has been shown to be a forecast of future cardiovascular events [45,46]. In studies with patients with acute coronary syndrome and chronic renal disease [47] or heart failure [48], the brachial-ankle PWV has been shown as a predictor of the prognosis for cardiovascular events [49].…”