Weight Reduction And Pharmocologic Treatment - Brief Article

Nutrition Research Newsletter, August, 2001 by K. Masuo, H. Mikami, T. Ogihara, M. Tuck

The risk for hypertension in obesity has been reported to be 50% to 300% higher than for normal-weight individuals. However, the underlying mechanisms of the blood pressure (BP) elevation in obesity-related hypertension remain unclear. The goal of the present study, recently published in the American Journal of Hypertension, was to clarify the mechanism of BP decrease achieved by weight loss, an ACE inhibitor (enalapril), and a long-acting CCB (amlodipine) in overweight and hypertensive patients. The researchers studied sequential changes in variables during weight loss and pharmacological treatments during 1 year, especially focusing on sympathetic activity and the plasma levels of insulin and leptin.

Five groups of 20 young (37 to 54 years), obese (BMI [is greater than] 26.0 kg/[m.sup.2]), male hypertensives each were treated with weight reduction alone, or with amlodipine or enalapril either with or without a weight reduction program. One reason for choosing a CCB and an ACE inhibitor was that they have contrasting effects on sympathetic activity. The five groups were matched in age, BMI, and BP levels at entry. The three groups on a weight reduction program either with or without pharmacological treatment were again divided into "weight loss groups" who either succeeded in weight reduction by 10% or more in BMI in the first 6 months and their BMI stabilizing or decreasing further during the next 6 months, and "nonweight loss groups" who failed to reduce weight ([is less than] 10%) in the first 6 months. Overall, all subjects were divided into eight study groups. Hypertension was defined as 160/95 mm Hg or higher. Weight reduction was achieved by a low caloric diet (1200 kcal/day) and exercise (at least 1 hour daily), typically swimming, walking, or jogging.

The success rate in weight loss was 65% for the weight reduction alone group, 60% in the ACE inhibitor and weight reduction group, and 40% in the CCB and weight reduction group at month 6. There was a significant difference between the success of weight reduction between the combined CCB and weight reduction group versus the weight-reduction-program-alone group. BMI in hypertensives with weight loss decreased significantly; however, BMI did not change in the pharmacological-treatment-alone groups.

Subjects receiving pharmocological treatments regardless of combined weight reduction reached the goal BP ([is less than] 140/90 mm Hg) at month 6. Blood pressure levels decreased significantly at month 3 in the eight study groups. The reductions in BP were greater in both pharmacological treatment groups than in the weight-loss-alone group. Pulse rate increased slightly in the CCB-alone group and the combined CCB and nonweight loss group at 3 and 6 months. In the combined CCB and weight loss group, pulse rate actually decreased at 12 months with the rate being equal to the reductions in pulse rate seen in the weight reduction group alone. On the other hand, in the ACE inhibitor group, pulse rate decreased throughout the study period regardless of weight loss.

Plasma insulin decreased significantly at month 3 in the weight loss group, but the reductions in insulin in the CCB-alone group and the combined CCB and nonweight-loss group were present only at 6 months. Plasma insulin decreased significantly at month 3 in the ACE inhibitor groups regardless of weight loss. There were significant reductions in plasma leptin in all eight study groups, even in hypertensives treated with drugs but nonweight loss. ACE inhibition had the most striking effect to lower plasma leptin.

The main findings in the present study were that weight loss has more favorable effects on hyperinsulinemia, hyperleptinemia, and stimulated sympathetic activity in obese hypertensive subjects than pharmacological treatment alone. It was determined that weight loss amplified the effects of ACE inhibitors and CCB on improving metabolic function and on the BP depressor effect of the pharmacological treatments. In addition, ACE inhibition had a more striking effect to lower plasma leptin than did other modalities of treatments, and finally normalization or suppression of sympathetic overactivity, and the attendant hyperinsulinemia and hyperleptinemia appeared to be the primary factor in reducing BP by weight loss. Based on these findings, weight loss should be regarded as an essential component of treatment programs for obesity-related hypertension. Weight loss reduced the dose of drugs needed to achieve the target BP.

K. Masuo, H. Mikami, T. Ogihara, M. Tuck. Weight Reduction and Pharmacologic Treatment in Obese Hypertensives. Am J Hypertens 14:530-538 (June 2001) [Correspondence: Toshio Ogihara, MD, Dept of Geriatric Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita City, Osaka, Japan. E-mail: ogihara@geriat.med.osaka-u.ac.jp].