Dr Nagahiro said: "Obesity is a risk factor for cardiovascular disease (CVD) but several studies have reported that low body mass index (BMI, kg/m2) was associated with worse cardiovascular outcome compared to middle or higher BMI. This strange phenomenon is called the 'obesity paradox' and has been described in patients with stroke, heart failure, coronary artery disease and renal disease."
He added: "The obesity paradox was reported in diabetic patients in 2012. Adults who were normal weight at the time of incident diabetes had higher mortality than adults who were overweight or obese.1 However, the relationship between obesity and cardiovascular events in patients with diabetes and hypertension is unknown."
The current study assessed the relationship between BMI and cardiovascular events in patients with hypertension and glucose intolerance. The researchers used data from the Nagoya Heart Study, a randomised trial comparing the efficacies of valsartan and amlodipine among 1,105 hypertensive patients with glucose intolerance in Japan. Patients were enrolled from October 2004 to January 2009 and the median follow-up was 3.2 years. The CVD endpoint was a composite of acute myocardial infarction, stroke, admission due to heart failure, coronary revascularization, or sudden cardiac death.
Patients were classified2 into four groups according to their baseline BMI: <23kg/m2 (n=283), 23 to 24.99kg/m2 (n=290), 25.00 to 27.49kg/m2 (n=277), and ≥27.50kg/m2 (n=255). Stratified analyses were performed according to these groups with the lowest BMI category as reference.
The primary endpoint occurred in 42 patients (14.8%, 4.6/100 patient-years) in the lowest BMI category (the reference group), 24 patients (8.3%, 2.3/100 patient-years) in the BMI 23.00 to 24.99kg/m2 group (hazard ratio [HR] =0.48), 27 patients (9.7%, 2.8/100 patient-years) in the BMI 25.00 to 27.49kg/m2 group (HR=0.57), and 13 patients (5.1%, 1.5/100 patient-years) in the highest BMI category (HR=0.32).
Dr Nagahiro said: "As BMI increased, CVD risk decreased among Japanese hypertensive patients with glucose intolerance. After adjustment for age, gender and smoking status, the lowest BMI group showed the highest CVD incidence and the highest BMI group had the lowest CVD incidence. CVD risk in the highest BMI group was less than one-third that of the lowest BMI group."
The Kaplan-Meier curve shows the proportion of patients who reached the primary endpoint over time (see figure). The maximum follow-up period was 2,126 days (5.8 years). Dr Nagahiro said: "Our study shows that there is an obesity paradox in hypertensive patients with glucose intolerance. This may be because of the severity of diabetes mellitus in the lowest BMI group. Baseline HbA1c and disease duration is similar to other groups however the percentage of insulin therapy is higher than other groups. This background indicates that the severity of diabetes mellitus is different. The two middle BMI groups had similar CVD risk, probably because mild obesity needs more time to exert an adverse effect on the cardiovascular system."
He concluded: "Hypertensive patients with glucose intolerance and a high BMI should lose weight and restore their BMI to normal range. The results of our study did not refute the fact that severe obesity is a CVD risk factor."