Long-term CHD Risk of Previously Obese Patients With T2DM
Long-term CHD Risk of Previously Obese Patients With T2DM
Mean age ± standard deviation of the 315 patients was 53.1 ± 6.6 years, mean MAXBMI ± standard deviation was 26.6 ± 3.4 kg/m, and mean BMI at enrollment ± standard deviation was 22.4 ± 2.7 kg/m.
Among the 315 patients who had no history of cardiovascular events at the start point, 48 of them developed coronary heart disease. Twenty-seven patients died without experiencing coronary heart disease and 168 were continuing to visit the hospital without having experienced coronary heart disease. Seventy-two patients had stopped visiting the hospital before January 2004 without having experienced coronary heart disease. The median observation period from the start of the observation to the endpoint was 13.9 years. The characteristics of the 315 patients at the start of the observation period are summarized in Table 1. Forty-eight had history of obesity. Ten of them had become obese before the age of thirty and another twenty of them had become obese before the age of forty.
At enrollment, patients with a MAXBMI greater than or equal to 30 kg/m had a larger BMI than patients with a MAXBMI less than 30 kg/m. Patients with a MAXBMI greater than or equal to 30 kg/m had higher HbA1c and lower HDL cholesterol values, but the difference was not statistically significant. Patients with a MAXBMI greater than or equal to 30 kg/m had a higher incidence of diabetic retinopathy than patients with a MAXBMI less than 30 kg/m. This result was consistent with the report of Ogawa et al..
The Kaplan-Meier analysis exhibited that coronary heart disease occurred more frequently in previously obese patients and that the effect seemed proportional over the follow-up periods (Figure 1B; MAXBMI compared with subjects in the reference category for the log-rank statistic; p = 0.0029). After stratification by gender, coronary heart disease occurred more frequently both in men and in women, but the results with women did not reach significance (Figure 1C and 1D). The occurrence of coronary heart disease of previously overweight patients was comparable to that of never-overweight patients (Figure 1B). In addition, the occurrence of coronary heart disease was not affected by BMI category at enrollment (Figure 1A).
(Enlarge Image)
Figure 1.
Kaplan-Meier survival curves from the probability of remaining free of coronary heart disease events. A: categorized by the body mass index (BMI) at enrollment, B: categorized by the maximal body mass index before enrollment (MAXBMI), C: categorized by the maximal body mass index before enrollment (MAXBMI) with diabetic men, D: categorized by the maximal body mass index before enrollment (MAXBMI) with diabetic women.
Next we used Cox regression models to examine the interaction of known risk factors as confounding factors with the incidence of cardiovascular events. Calculation by multivariate Cox regression models exhibited a presumable threshold effect rather than a graded increase of MAXBMI, suggesting unrecognized factors acted with regard to previous obesity. Hazard ratios and corresponding 95% confidence intervals of coronary heart disease for patients with previous obesity compared with subjects in the reference category (22 < or = MAXBMI < 25) were 2.52 and 1.15 to 5.50 (p value = 0.020) after adjustment for age and sex with additional adjustment for smoking status, serum lipids, and blood pressure (Table 2).
In the present cohort, a larger decrease of BMI before enrollment was observed in patients with larger MAXBMI (Table 1). The differences between BMI at enrollment and MAXBMI (deltaBMI) strongly correlated with MAXBMI values (Pearson's correlation coefficient = 0.64) and deltaBMI also related with the occurrence of coronary heart disease. The hazard ratios by the increment of one standard deviation of deltaBMI (2.62 kg/m) were calculated as 1.38 (95% confidence intervals: 1.08 to 1.79; p value = 0.013) after adjustment for age, sex, smoking status, serum lipids, and blood pressure (Table 3). The association became weak after adjustment for HbA1c at enrollment (Table 3), suggesting that prolonged poor glycemic control was in part related to the patients with a large deltaBMI.
Results
Patients
Mean age ± standard deviation of the 315 patients was 53.1 ± 6.6 years, mean MAXBMI ± standard deviation was 26.6 ± 3.4 kg/m, and mean BMI at enrollment ± standard deviation was 22.4 ± 2.7 kg/m.
Among the 315 patients who had no history of cardiovascular events at the start point, 48 of them developed coronary heart disease. Twenty-seven patients died without experiencing coronary heart disease and 168 were continuing to visit the hospital without having experienced coronary heart disease. Seventy-two patients had stopped visiting the hospital before January 2004 without having experienced coronary heart disease. The median observation period from the start of the observation to the endpoint was 13.9 years. The characteristics of the 315 patients at the start of the observation period are summarized in Table 1. Forty-eight had history of obesity. Ten of them had become obese before the age of thirty and another twenty of them had become obese before the age of forty.
At enrollment, patients with a MAXBMI greater than or equal to 30 kg/m had a larger BMI than patients with a MAXBMI less than 30 kg/m. Patients with a MAXBMI greater than or equal to 30 kg/m had higher HbA1c and lower HDL cholesterol values, but the difference was not statistically significant. Patients with a MAXBMI greater than or equal to 30 kg/m had a higher incidence of diabetic retinopathy than patients with a MAXBMI less than 30 kg/m. This result was consistent with the report of Ogawa et al..
The Kaplan-Meier Analysis
The Kaplan-Meier analysis exhibited that coronary heart disease occurred more frequently in previously obese patients and that the effect seemed proportional over the follow-up periods (Figure 1B; MAXBMI compared with subjects in the reference category for the log-rank statistic; p = 0.0029). After stratification by gender, coronary heart disease occurred more frequently both in men and in women, but the results with women did not reach significance (Figure 1C and 1D). The occurrence of coronary heart disease of previously overweight patients was comparable to that of never-overweight patients (Figure 1B). In addition, the occurrence of coronary heart disease was not affected by BMI category at enrollment (Figure 1A).
(Enlarge Image)
Figure 1.
Kaplan-Meier survival curves from the probability of remaining free of coronary heart disease events. A: categorized by the body mass index (BMI) at enrollment, B: categorized by the maximal body mass index before enrollment (MAXBMI), C: categorized by the maximal body mass index before enrollment (MAXBMI) with diabetic men, D: categorized by the maximal body mass index before enrollment (MAXBMI) with diabetic women.
Cox Regression Models
Next we used Cox regression models to examine the interaction of known risk factors as confounding factors with the incidence of cardiovascular events. Calculation by multivariate Cox regression models exhibited a presumable threshold effect rather than a graded increase of MAXBMI, suggesting unrecognized factors acted with regard to previous obesity. Hazard ratios and corresponding 95% confidence intervals of coronary heart disease for patients with previous obesity compared with subjects in the reference category (22 < or = MAXBMI < 25) were 2.52 and 1.15 to 5.50 (p value = 0.020) after adjustment for age and sex with additional adjustment for smoking status, serum lipids, and blood pressure (Table 2).
In the present cohort, a larger decrease of BMI before enrollment was observed in patients with larger MAXBMI (Table 1). The differences between BMI at enrollment and MAXBMI (deltaBMI) strongly correlated with MAXBMI values (Pearson's correlation coefficient = 0.64) and deltaBMI also related with the occurrence of coronary heart disease. The hazard ratios by the increment of one standard deviation of deltaBMI (2.62 kg/m) were calculated as 1.38 (95% confidence intervals: 1.08 to 1.79; p value = 0.013) after adjustment for age, sex, smoking status, serum lipids, and blood pressure (Table 3). The association became weak after adjustment for HbA1c at enrollment (Table 3), suggesting that prolonged poor glycemic control was in part related to the patients with a large deltaBMI.