The importance of body mass index and weight-change in patients with coronary artery disease

Abstract: High body mass index (BMI) is associated with cardiovascular risk factors such as hypertension, dyslipidemia, and insulin resistance. Obesity is also an independent risk factor for coronary artery disease (CAD) and can cause structural as well as functional changes in the heart. High BMI is associated with increased mortality in the population. Weight-loss from a state of overweight or obesity may reverse some of the alternations associated with excess weight. However, the survival benefit of weight-loss among the population is still uncertain. The aims of this thesis were to examine the prognostic importance of BMI and weight-change in patients with CAD. A total of 12 550 patients with CAD, 94% with prior acute myocardial infarction (AMI), were included in our post-hoc analyses. Patients were recruited from 3 large clinical trials in which weight and height were measured. Mean follow-up ranged from 6 months to 5.4 years. Patients were categorized into 4 groups according to baseline BMI: underweight (< 22.00 kg/m2), normal-weight (22.00-24.99 kg/m2), overweight (25.00-29.99 kg/m2), obese (>/= 30 kg/m2). Patients were divided into 3 groups with regard to weight-change; weight-loss, weight-stability and weight-gain. Weight-change was pre-defined as weight-gain or weight-loss from baseline of > 0.1 kg per baseline BMI-unit. Consequently, for a patient with a BMI of 25 kg/m2, a change of >±2.5 kg was categorized as a weight-change. This corresponds to 3-3.5% change in total body-weight. Weight-change was assessed after 3-12 months. One of the main findings in this thesis was that among patients with CAD, being overweight or obese was not associated with increased mortality or morbidity risk, compared to being normal-weight. Being underweight was significantly associated with increased mortality risk compared to being normal-weight. The prognostic impact of BMI was related to time of follow-up as well as the inherent risk of the patient. It seems that obesity might be hazardous during longer period of follow-up and when the inherent risk of the patient is low. Another finding is that the association between BMI and prognosis was related to treatment with neurohormonal blockade, i.e. ACE inhibitors and betablockers. Increased activation of the renin angiotensin system and the sympathetic nervous system is common in patients with CAD. Being overweight or obese was associated with decreased survival among patients not receiving neurohormonal blockade. Among patients receiving neurohormonal blockade, overweight and obese patients did not have increased mortality compared to normal-weight patients. Weight-loss was not associated with survival benefits among patients with CAD. Compared to weight-stability, weight-loss was rather associated with increased mortality, independent of baseline BMI. Weight-gain had similar risk compared to weight-stability. The reasons for these observations are likely multifactorial. Importantly, our findings do not preclude a benefit of weight-loss in response to exercise training as part of a cardiac rehabilitation program. Our observations expand the knowledge about how BMI and body weight-change are related to the prognosis in patients with stable CAD and following AMI. These findings reinforce the need for a better understanding of the importance of BMI and the complexity of weight-change to the prognosis among these patients. Our data do not indicate that obesity is a negative factor in patients with CAD today, whereas underweight is. Further, our observations indicate that weight-loss in patients with established CAD should render every doctor's attention and underlying reasons should be explored. These associations and their causes should be further assessed in future investigations. Meanwhile, we believe that our main focus should be on preventing obesity early in life. In other words, obesity should be prevented rather than treated.