The Effect of Age and NT-proBNP on the Association of Central Obesity with 6-Years Cardiovascular Mortality of Middle-Aged and Elderly Diabetic People: The Population-Based Casale Monferrato Study

BACKGROUND: Among people with type 2 diabetes the relationship between central obesity and cardiovascular mortality has not been definitely assessed. Moreover, NT-proBNP is negatively associated with central obesity, but no study has examined their combined effect on survival. We have examined these issues in a well-characterized population-based cohort. METHODS AND FINDINGS: Survival data of 2272 diabetic people recruited in 2000 who had no other chronic disease have been updated to 31 December 2006. NT-proBNP was measured in a subgroup of 1690 patients. Cox proportional hazards modeling was employed to estimate the independent associations between cardiovascular and all-cause mortality and waist circumference. Mean age was 67.9 years, 49.3% were men. Both age and NT-proBNP were negatively correlated with waist circumference (r = -0.11, p<0.001 and r = -0.07, p = 0.002). Out of 2272 subjects, 520 deaths (221 for CV mortality) occurred during a median follow-up of 5.4 years. Central obesity was not associated with CV mortality (hazard ratio, HR, adjusted for age, sex, diabetes duration, 1.14, 95% CI 0.86-1.52). NTproBNP was a negative confounder and age a strong modifier of this relationship (p for interaction<0.001): age<70 years, fully adjusted model HR = 3.52 (1.17-10.57) and age ≥70 years, HR = 0.80 (0.46-1.40). Respective HRs for all-cause mortality were 1.86 (1.03-3.32) and 0.73 (0.51-1.04). CONCLUSIONS: In diabetic people aged 70 years and lower, central obesity was independently associated with increased cardiovascular mortality, independently of the negative effect of NT-proBNP. In contrast, no effect on 6-years survival was evident in diabetic people who have yet survived up to 70 years

Circulating anti-Hsp70 levels in nascent metabolic syndrome: the Casale Monferrato Study.

The metabolic syndrome (MetS) confers an increased risk of both type 2 diabetes and cardiovascular diseases (CVD). Heat shock protein 70 (Hsp70), an intracellular polypeptide, can be exposed on the plasma membrane and/or released into the circulation, eliciting both native and immune responses that may contribute to vascular damage. Our aim was to assess if serum anti-Hsp70 antibody levels were cross-sectionally associated with uncomplicated MetS. A cross-sectional case–control study from the nondiabetic cohort of the Casale Monferrato Study was performed. Subjects with established CVD and/or abnormal renal function were excluded. Case subjects (n = 180) were defined as those fulfilling the criteria for the diagnosis of MetS. Control subjects (n = 136) were completely free of any component of the MetS. Serum anti-Hsp70 levels were measured by immunoenzymatic assay. We found that anti-Hsp70 antibody levels were significantly higher in cases than in control subjects [122.6 (89.5–155.6) vs 107.1 (77.3–152.4) μg/ml, p = 0.04], even after age and sex adjustment. In logistic regression analysis, higher levels of log-anti-Hsp70 conferred greater odds ratio (OR) for MetS, independently of age and sex. There was a statistically significant trend of ORs across quartiles of anti-Hsp70 and values greater than 108.0 μg/ml conferred a 77 % increased OR of MetS as compared with values in the lower quartiles. The strength of the association slightly decreased after further adjustment for apolipoprotein B, smoking, and albumin excretion rate. In conclusion, our results show that serum anti-Hsp70 antibody levels are independently associated with nascent MetS