Hector O. Ventura

Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss.

Obesity has reached global epidemic proportions in both adults and children and is associated with numerous comorbidities, including hypertension (HTN), type II diabetes mellitus, dyslipidemia, obstructive sleep apnea and sleep-disordered breathing, certain cancers, and major cardiovascular (CV) diseases. Because of its maladaptive effects on various CV risk factors and its adverse effects on CV structure and function, obesity has a major impact on CV diseases, such as heart failure (HF), coronary heart disease (CHD), sudden cardiac death, and atrial fibrillation, and is associated with reduced overall survival. Despite this adverse association, numerous studies have documented an obesity paradox in which overweight and obese people with established CV disease, including HTN, HF, CHD, and peripheral arterial disease, have a better prognosis compared with nonoverweight/nonobese patients. This review summarizes the adverse effects of obesity on CV disease risk factors and its role in the pathogenesis of various CV diseases, reviews the obesity paradox and potential explanations for these puzzling data, and concludes with a discussion regarding the current state of weight reduction in the prevention and treatment of CV diseases.

Omega-3 polyunsaturated fatty acids and cardiovascular diseases.

Omega-3 polyunsaturated fatty acid (omega-3 PUFA) therapy continues to show great promise in primary and, particularly in secondary prevention of cardiovascular (CV) diseases. The most compelling evidence for CV benefits of omega-3 PUFA comes from 4 controlled trials of nearly 40,000 participants randomized to receive eicosapentaenoic acid (EPA) with or without docosahexaenoic acid (DHA) in studies of patients in primary prevention, after myocardial infarction, and most recently, with heart failure (HF). We discuss the evidence from retrospective epidemiologic studies and from large randomized controlled trials showing the benefits of omega-3 PUFA, specifically EPA and DHA, in primary and secondary CV prevention and provide insight into potential mechanisms of these observed benefits. The target EPA + DHA consumption should be at least 500 mg/day for individuals without underlying overt CV disease and at least 800 to 1,000 mg/day for individuals with known coronary heart disease and HF. Further studies are needed to determine optimal dosing and the relative ratio of DHA and EPA omega-3 PUFA that provides maximal cardioprotection in those at risk of CV disease as well in the treatment of atherosclerotic, arrhythmic, and primary myocardial disorders.

Hypertension and sudden death: Increased ventricular ectopic activity in left ventricular hypertrophy

The present study was designed to detect and quantify cardiac arrhythmias in hypertensive patients with left ventricular hypertrophy. Continuous ambulatory electrocardiographic tracings and arterial pressure were recorded for 24 hours in 14 normotensive subjects, 10 patients with established essential hypertension without left ventricular hypertrophy, and 16 hypertensive patients with left ventricular hypertrophy by electrocardiographic criteria. Urinary excretion of norepinephrine was simultaneously measured over four successive four-hour and one eight-hour period. Patients with left ventricular hypertrophy had significantly more ventricular (but not atrial) premature contractions than those without left ventricular hypertrophy or than normotensive subjects. Five patients with left ventricular hypertrophy had episodes of more than 30 premature ventricular contractions per minute. Higher-grade ventricular ectopic activity such as coupled premature ventricular contractions was seen in two, and multifocal premature ventricular contractions were seen in three in the group with left ventricular hypertrophy. No difference in urinary catecholamine excretion rates among the three groups was seen. Left ventricular hypertrophy has been shown to be an independent risk factor for sudden death and acute myocardial infarction. Electrocardiographic monitoring of patients with left ventricular hypertrophy allows identification of those who have the highest risk and, therefore, require the most aggressive therapeutic intervention.

Dimorphic Cardiac Adaptation to Obesity and Arterial Hypertension

Cardiovascular function and structure were evaluated by M-mode echocardiography and systemic hemodynamics in paired lean and obese patients, either hypertensive or normotensive. Compared to lean patients, obese patients had greater left atrial (p less than 0.0001), ventricular (p less than 0.001), and aortic root (p less than 0.002) diameters; posterior and septal wall thickness (p less than 0.001); and ventricular mass, cardiac output, stroke volume, and stroke work (all p less than 0.0001). Hypertensive patients had increased posterior wall thickness, end diastolic wall stress, stroke work (p less than 0.01), and a lower radius to posterior wall thickness ratio indicating concentric hypertrophy (p less than 0.001) when compared to normotensive patients. Cardiac adaptation to obesity consists of left ventricular dilatation and hypertrophy (eccentric hypertrophy) irrespective of arterial pressure levels. In contrast, essential hypertension solely produces concentric hypertrophy. Both obesity and hypertension increase left ventricular stroke work by disparate hemodynamic mechanisms; their presence in the same patient will tax the heart and increase the long-term risk of congestive failure.

Impact of Obesity and the Obesity Paradox on Prevalence and Prognosis in Heart Failure

Obesity has reached epidemic proportions in the United States and worldwide. Considering the adverse effects of obesity on left ventricular (LV) structure, diastolic and systolic function, and other risk factors for heart failure (HF), including hypertension and coronary heart disease, HF incidence and prevalence, not surprisingly, is markedly increased in obese patients. Nevertheless, as with most other cardiovascular diseases, numerous studies have documented an obesity paradox, in which overweight and obese patients, defined by body mass index, percent body fat, or central obesity, demonstrate a better prognosis compared with lean or underweight HF patients. This review will describe the data on obesity in the context of cardiopulmonary exercise testing in HF. Additionally, the implications of obesity on LV assist devices and heart transplantation are reviewed. Finally, despite the obesity paradox, we address the current state of weight reduction in HF.

Photopheresis for the Prevention of Rejection in Cardiac Transplantation

BACKGROUND Photopheresis is an immunoregulatory technique in which lymphocytes are reinfused after exposure to a photoactive compound (methoxsalen) and ultraviolet A light. We performed a preliminary study to assess the safety and efficacy of photopheresis in the prevention of acute rejection of cardiac allografts. METHODS A total of 60 consecutive eligible recipients of primary cardiac transplants were randomly assigned to standard triple-drug immunosuppressive therapy (cyclosporine, azathioprine, and prednisone) alone or in conjunction with photopheresis. The photopheresis group received a total of 24 photopheresis treatments, each pair of treatments given on two consecutive days, during the first six months after transplantation. The regimen for maintenance immunosuppression, the definition and treatment of rejection episodes, the use of prophylactic antibiotics, and the schedule for cardiac biopsies were standardized among all 12 study centers. All the cardiac-biopsy samples were graded in a blinded manner at a central pathology laboratory. Plasma from the subgroup of 34 patients (57 percent) who were enrolled at the nine U.S. centers was analyzed by polymerase-chain-reaction amplification for cytomegalovirus DNA. RESULTS After six months of follow-up, the mean (+/-SD) number of episodes of acute rejection per patient was 1.44+/-1.0 in the standard-therapy group, as compared with 0.91+/-1.0 in the photopheresis group (P=0.04). Significantly more patients in the photopheresis group had one rejection episode or none (27 of 33) than in the standard-therapy group (14 of 27), and significantly fewer patients in the photopheresis group had two or more rejection episodes (6 of 33) than in the standard-therapy group (13 of 27, P=0.02). There was no significant difference in the time to a first episode of rejection, the incidence of rejection associated with hemodynamic compromise, or survival at 6 and 12 months. Although there were no significant differences in the rates or types of infection, cytomegalovirus DNA was detected significantly less frequently in the photopheresis group than in the standard-therapy group (P=0.04). CONCLUSIONS In this pilot study, the addition of photopheresis to triple-drug immunosuppressive therapy significantly decreased the risk of cardiac rejection without increasing the incidence of infection.

Enalapril improves systemic and renal hemodynamics and allows regression of left ventricular mass in essential hypertension

Enalapril, a new angiotensin-converting enzyme inhibitor, is an effective antihypertensive agent for both renovascular and essential hypertension. It is structurally different from captopril in that it does not possess a sulfhydryl group. The systemic and renal hemodynamic, biochemical and cardiac adaptive changes induced by enalapril were studied in 8 patients with essential hypertension before and after 12 weeks of therapy. Mean arterial pressure decreased from 110 to 90 mm Hg (p less than 0.01), and this was mediated through a decrease in total peripheral resistance from 42 +/- 3 to 32 +/- 3 U (p less than 0.01). Cardiac index and heart rate did not change. Renal plasma flow was increased in 6 of 8 patients and renal vascular resistance decreased from 123 +/- 6 to 91 +/- 7 U (p less than 0.001). Left ventricular mass index decreased from a mean of 166 +/- 29 to 117 +/- 8 g/m2 (p less than 0.05) without impaired myocardial contractility. Thus, enalapril lowers arterial pressure by reducing total peripheral resistance without reflexive cardiac effects. It also has favorable hemodynamic effects on the kidney. This is the first report of regression of LV mass with this agent in man.

Borderline hypertension and obesity: two prehypertensive states with elevated cardiac output.

Systemic, renal and splanchnic hemodynamics, intravascular volume, circulating catecholamine levels and plasma renin activity were compared in 39 patients with borderline hypertension and 28 normotensive subjects, who were less than 5% (n = 42, lean patients) or more than 40% overweight (n = 25, obese patients). Lean borderline hypertensive patients had greater cardiac output (p < 0.05), heart rate (p < 0.01) and renal blood flow (p < 0.05); cardiopulmonary redistribution of intravascular volume (p < 0.05); and higher circulating norepinephrine levels (p < 0.05). Obese normotensive subjects also showed an increased cardiac output (p < 0.005), stroke volume (p < 0.01), left ventricular stroke work (p < 0.05), and renal blood flow (p < 0.05) (but not respective indexes), but intravascular volume was expanded (p < 0.05) without redistribution and circulating catecholamine levels were normal. Obese borderline hypertensive patients had hemodynamic characteristics similar to those of obese normotensive subjects except for an increased peripheral resistance (p < 0.05). The data indicate that although both populations have an increased cardiac output, the lean borderline hypertensive patients have signs of enhanced adrenergic activity as evidenced by higher circulating catecholamine levels and heart rate with blood volume translocation to the cardiopulmonary circulation. In contrast, the obese subjects (whether normotensive or borderline hypertensive), who also have increased cardiac output, seem to have normal adrenergic activity and an expanded intravascular volume without cardiopulmonary redistribution.

Diurnal variation of blood pressure in elderly patients with essential hypertension

Twenty‐one elderly patients with essential hypertension, all over 65 years of age, were subjected to automated noninvasive 24‐hour blood pressure measurement. Readings were obtained every 7.5 minutes throughout the day. The data were analyzed with respect to: correlation between office and ambulatory pressure measurements; possible differences in the circadian blood pressure pattern; and the existence of hypertensive or atherosclerotic cardiovascular complications. In all patients, the office systolic pressures were significantly higher than the ambulatory daytime pressures; diastolic pressures were similar. At night, two patterns of blood pressure emerged. In one there was a further fall in both systolic and diastolic pressures to normotensive levels, whereas the other pattern revealed no change in diastolic pressure, although systolic pressure increased significantly to similar levels as measured in the office. The prevalence of hypertensive or atherosclerotic cardiovascular complications in the patients with the first pattern was significantly less than in the group of patients with the second pattern (chi square, P < 0.025). The data reported herein indicate that ambulatory blood pressure monitoring may help in the overall clinical evaluation of elderly patients with hypertension.

Racial differences in cardiac adaptation to essential hypertension determined by echocardiography indexes

Epidemiologic data point to racial differences in cardiac adaptation to hypertension. In this study, echocardiography and measurement of systemic hemodynamics were performed in 30 black and 30 white patients with untreated essential hypertension. Each black patient was matched with a white patient for age, sex and mean arterial pressure. Wall thickness measurements were similar, but left ventricular mass index was significantly increased in blacks (probability [p] less than 0.05). There was a nonsignificant increase in the number of black patients with posterior wall thickness greater than 1.1 cm. Only in black patients was posterior wall thickness related to systolic (r = 0.45; p = 0.008) and diastolic (r = 0.44; p = 0.0042) pressure and to total peripheral resistance (r = 0.32; p less than 0.046). Thus, although ventricular wall thickness changes are similar in black and white patients, qualitative differences exist in the cardiac adaptive process to systemic hypertension.