Synergistic effects of glucose tolerance and BMI on cardiovascular events and all-cause mortality in a healthy population: CA.ME.LI.A study 7 years follow-up.

The CA.ME.LI.A (CArdiovascular risks, MEtabolic syndrome, LIver and Autoimmune disease) epidemiological study was conducted in Abbiategrasso (Milan, Italy) to identify risk factors for metabolic and cardiovascular disease in an apparently healthy population of northern Italy. The population (n = 2,545, 1,251 men, 1,254 women) was stratified according to body mass index [normal body weight (NBW): <25 kg/m²; overweight-obese (OWO): ≥25 kg/m²] and according to fasting blood glucose [normal fasting glucose: <100 mg/dL; impaired fasting glucose (IFG): 100-125 mg/dL; diabetes mellitus (DM): ≥126 mg/dL]. The incidence of cardiovascular (CV) events and overall mortality were studied by the Kaplan-Meier method using the log rank test. Univariate analysis was conducted with time-dependent Cox models. During the 7-yr follow-up period, 80 deaths and 149 CV events occurred. IFG [hazard ratio (HR): 2.81; confidence interval (CI): 1.37-5.77; P = 0.005], DM (HR: 4.88; CI: 1.47-16; P = 0.010), or OWO (HR: 2.78; CI:1.68-4.59; P < 0.001) all produced significant increases in CV events and deaths. In the combination IFG/OWO (HR: 5.51; CI: 3.34-9.08; P < 0.001), there was an apparent additive effect of the two conditions, whereas in the combination DM/OWO (HR: 12.71; CI: 7.48-22; P < 0.001), there was an apparent multiplicative effect on the risk for CV events and deaths. In males, the DM/NBW group had a higher incidence of cardiovascular events and deaths than the IFG/OWO group. In contrast, in females, the IFG/OWO group had a higher incidence of cardiovascular events and deaths than the DM/NBW group. In women, there was a greater incidence of CV events in the IFG/OWO group (HR: 6.23; CI: 2.88-13; P < 0.001) than in men in the same group (HR: 4.27; CI: 2.15-8.47; P < 0.001). Consistent with these data, also all-cause mortality was progressively increased by IFG/DM and OWO, with an apparently exponential effect in the combination DM/OWO (HR: 11.78; CI: 6.11-23; P < 0.001). IFG/DM and OWO, alone or in combination, had major effects in increasing mortality for all causes and CV events. The relative contributions of hyperglycemia and overweight/obesity on cardiovascular events and deaths were apparently, to a certain extent, sex dependent. Females were more affected by overweight/obesity either alone or combined with IFG, as compared with males.NEW & NOTEWORTHY For the first time, the combined effects of glucose tolerance and BMI have been investigated in an apparently healthy large population sample of a city in the north of Italy. We found that there are synergistic effects of glucose levels with BMI to increase not only cardiovascular events and deaths but also cancer-related deaths and all-cause mortality.