Obesity and cardiovascular disease

Martin A. Alpert
Department of Medicine, St John’s Mercy Medical Center, St Louis, Mo, USA
Southern Illinois University School of Medicine, Springfield, Ill, USA
University of Missouri School of Medicine, Columbia, Mo, USA
Correspondence: Professor Martin Alpert, St John’s Mercy Medical Center, 621 S. New Ballas Road, Suite 3019-B, St Louis, MO 63141, USA.
Tel: +1 3145696959 , fax: +1 3145696272, e-mail: ALPEMA@stlo.smhs.com

Abstract

Obesity affects the heart in two major ways. It produces hemodynamic and cardiac structural changes that may alter left ventricular function. These alterations are most pronounced in severely obese persons and may predispose to congestive heart failure in such individuals. Obesity also affects the heart through its association with coronary heart disease. This report describes the alterations in cardiac performance and morphology associated with obesity, discusses their clinical sequelae, and reviews the evidence linking obesity to coronary heart disease.
- Heart Metab. 2002;17:8–10.

Keywords: Obesity cardiomyopathy, congestive heart failure, eccentric left ventricular hypertrophy, cardiovascular risk factors, coronary artery disease

Effects of obesity on cardiac performance and morphology
Obesity, particularly severe obesity, produces a variety of alterations in cardiac function and morphology [1–27]. When obesity is severe and chronic, these abnormalities may cause congestive heart failure [1–22].

Cardiac hemodynamics, cardiac morphology, and left ventricular function with obesity
Due to the intense vascularity of fat and to a decrease in systemic vascular resistance, there is a linear increase in total blood volume and cardiac output with increasing adipose accumulation. Since there is no change in heart rate, the augmentation of cardiac output is attributable to an increase in stroke volume [3–6]. Cardiac work rises in excess of that predicted for ideal body weight due to an increase in stroke work [6]. Oxygen consumption increases and the arteriovenous oxygen difference widens due to the avid metabolic activity of fat [5, 6]. There is a leftward shift in the Frank-Starling curve due to incremental increases in left ventricular pressure and volume [7]. Left ventricular end-diastolic pressure is elevated in many, but not all, severely obese individuals [6–9]. Right heart pressures are also commonly elevated, presumably due to similar hemodynamic alterations or left heart failure [6–9].
Hypertension occurs in 60% of obese persons [4]. Cardiac hemodynamic alterations in such individuals are as previously described except for disproportionately elevated left ventricular stroke work [4, 10]. Systemic vascular resistance is higher than in normotensive obese persons but is lower than that expected in hypertensive lean individuals [4, 10]. The coexistence of systemic hypertension and obesity imparts a double burden on the heart due to a simultaneous increase in afterload and preload [4, 10].
Exercise is able to produce an increase in oxygen intake and cardiac output at mild to moderate workloads but falls toward normal with higher workloads [4, 11]. With exercise, left ventricular end-diastolic pressure often exceeds 20 mm Hg in obese individuals, thus predisposing to pulmonary congestion [4, 11].
The aforementioned hemodynamic alterations may produce changes in cardiac morphology and left ventricular function, particularly in those who are more severely and chronically (usually ³15 years) obese [12–18]. The increase in total blood volume and cardiac output leads to left ventricular dilatation [4, 12]. Such hypercirculation may also contribute to enlargement of the left atrium, right ventricle, and right atrium [12]. Dilatation of the left ventricle produces an increase in left ventricular wall stress in accordance with the law of Laplace [4, 12]. This leads to secondary or “eccentric” hypertrophy which is characterized by a high left ventricular radius/thickness or volume/mass ratio and is an attempt to normalize left ventricular wall stress [4, 12]. If wall stress normalizes (adequate hypertrophy), diastolic dysfunction may occur, but systolic function remains normal [14, 18]. If wall stress remains chronically high (inadequate hypertrophy), left ventricular systolic dysfunction may ensue [4, 16, 17]. In hypertensive obese individuals, left ventricular volume is lower and left ventricular wall thickness is greater than in normotensive obese persons, suggesting a hybrid form of hypertrophy [12]. Myocardial fat infiltration, when present, does not typically predispose to left ventricular dysfunction [12].
Most, but not all, of the aforementioned hemodynamic and cardiac structural alterations associated with obesity are reversible with substantial weight loss [4, 12, 16, 18–22]. Total blood volume, oxygen consumption, cardiac output, stroke volume, and systemic blood pressure all decrease with weight reduction [4]. In contrast, systemic vascular resistance changes little (if at all), left ventricular end-diastolic pressure commonly remains elevated, and myocardial wall compliance tends to remain abnormal [4]. Weight loss may also fail to fully normalize elevated right heart pressures [4]. There is convincing evidence that substantial weight reduction in severely obese individuals produces regression of left ventricular hypertrophy, improvement of cardiac Doppler-derived indices of left ventricular diastolic dysfunction, and improvement of left ventricular systolic dysfunction in those with impaired systolic function prior to weight loss [12, 16, 18, 20–22].
It is important to emphasize that most of the information concerning cardiac function and morphology in obesity has been derived from studies of severely obese patients. Data derived from studies of mildly to moderately obese subjects are less consistent.

Obesity cardiomyopathy
Obesity cardiomyopathy is the clinical syndrome of congestive heart failure that evolves from the cardiac functional and structural alterations described in the previous section [23]. The syndrome of obesity cardiomyopathy is seen exclusively in severely obese individuals [23]. Left heart failure predominates [23]; right heart failure occurs as a result of hypercirculation and left heart failure [23]. In some cases, pulmonary hypertension associated with hypoxia due to sleep apnea with or without alveolar hypoventilation may contribute to right heart failure [23]. Sleep apnea occurs in more than 50%, and clinically important alveolar hypoventilation in 5% to 10% of severely obese individuals [23].
Early on, weight gain precedes and then accompanies progressive dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, lower-extremity edema, and, in some cases, increased abdominal girth [23–26]. These episodes may wax and wane with changes in body weight. Initially, these symptoms occur in the presence of impaired left ventricular diastolic function and normal left ventricular systolic function [23–26]. When symptoms of pulmonary and systemic congestion become persistent, left ventricular systolic dysfunction becomes more prevalent [23]. In those with obesity hypoventilation syndrome (sometimes referred to as “Pickwickian” syndrome), there is an accentuation of symptoms of right heart failure which in the advanced stages may be accompanied by somnolence, confusion, disorientation, or coma [23–26]. Physical findings in obesity cardiomyopathy include gallop rhythm (atrial and ventricular), pulmonary crackles, jugular venous distension, hepatojugular reflux, lower extremity edema, and ascites. In those with obesity hypoventilation syndrome, the aforementioned signs may be accompanied by cyanosis, Cheyne-Stokes respiration, conjunctival suffusion, retinal venous congestion, and papilledema [23–26].
Acute episodes of congestive heart failure are treated with dietary salt restriction, low-flow inspired oxygen, and diuretics [23]. Angiotensin-converting enzyme inhibitors should be employed when left ventricular systolic function is depressed and may be used for systemic hypertension [23]. Digitalis may be useful in patients with atrial fibrillation (for rate control) or in those with left ventricular systolic dysfunction [23]. The role of such drugs as angiotensin receptor blockers, hydralazine, nitrates, spironolactone, and
b-blockers in obesity cardiomyopathy has not been established.
Although there is clearcut evidence that substantial weight loss produces regression of left ventricular hypertrophy and improvement of both left ventricular diastolic filling and left ventricular systolic function when such abnormalities are present, information is sparse concerning the effect of weight loss on congestive heart failure in patients with obesity cardiomyopathy [16, 18]. Several case reports and two small series suggest that the clinical manifestations of obesity hypoventilation syndrome can be reversed with substantial weight loss [23–27]. Another small study documented improvement in NYHA functional class following substantial weight loss in most patients with severe obesity and congestive heart failure but without hypoventilation [26].

Obesity and coronary heart disease
Obesity has long been cited as a cardiovascular risk factor [28–45]. While its relation to multiple traditional and nontraditional cardiovascular risk factors is unquestioned, the role of obesity as an independent risk factor is less certain. Methods used to determine the relation between obesity and coronary heart disease include: (1) epidemiologic studies relating morbidity or mortality to some measure of total body fat or fat distribution (including those designed to determine if obesity is an independent risk factor); (2) cross-sectional studies assessing the relation of body fat to coronary anatomy; and (3) studies determining the relation of obesity to cardiovascular risk factors [28].

Epidemiologic studies
There is an impressive body of epidemiologic evidence relating obesity to coronary heart disease and cardiovascular mortality. Obesity was a powerful predictor of coronary heart disease in studies of 1000 to 2000 middle-aged men followed for 10 to 18 years whose relative weight was above 140% or whose body mass index (BMI) was above 30 kg/m2 [28]. The Honolulu Heart Program and Paris Prospective Study showed that for any given BMI, the risk of coronary heart disease increased twofold with successfully higher quintiles and deciles of the Trunk Fat Index [ 3130,]. The Normative Aging Study showed an inverse correlation between age at onset of obesity and the probability of developing coronary heart disease [28]. The Framingham Heart Study and the Manitoba Study identified obesity as an independent risk predictor for coronary heart disease after 26 years of follow-up, particularly in women [32, 33]. The Study of Men Born in 1913 and several smaller studies have identified central obesity as an independent risk factor for coronary heart disease [34].
In contrast, the Pooling Project showed no clear aged-adjusted or age-specific association between obesity and coronary heart disease mortality [28]. In the Twin Cities Prospective Study, 284 healthy middle-aged men were followed for up to 35 years [28]. No obesity index discriminated those who lived from those who died. In the Charleston Heart Study, neither BMI nor fat patterning predicted coronary heart disease mortality during 25 years of follow-up [28].
Criticisms of epidemiologic studies, which may help to explain these conflicting results, include: (1) failure to control for cardiovascular risk factors; (2) failure to include some cardiovascular risk factors in the analysis; (3) misclassification bias; (4) small cohort size and short-term follow-up; and (5) dilution of the influence of high-risk groups by inclusion of all obese subjects [28].

Anatomic studies
Anatomic studies attempting to relate obesity to coronary heart disease have similarly produced conflicting results [28]. A large autopsy study of male accident victims aged 25 to 64 years showed a weak correlation between abdominal panniculus size and the presence of raised coronary lesions in Caucasian but not African-American men [28]. In another postmortem study, coronary heart disease severity was greater and catastrophic coronary heart disease events were more frequent in obese men but not in obese women [28]. In an autopsy study of Japanese-Americans there was a positive correlation between coronary heart disease and relative weight greater than 116% [28]. An autopsy study of 1260 patients showed that advanced coronary heart disease was twice as common in those with an abdominal panniculus greater than 3 cm than in those with poor or average nutritional status [28]. In another study, the severity of coronary atherosclerosis correlated positively with the size of adipocytes but not with the number of fat cells, suggesting that environmental factors may be more important than genetic influences in the development of coronary heart disease in obese individuals [28].
In contrast, several postmortem studies have reported no difference in the frequency of coronary heart disease death or morbidity in men and women based on obesity indexes [28]. Moreover, 12 studies using coronary angiography as a diagnostic probe have failed to demonstrate a consistent relation between obesity and coronary heart disease [28].

Obesity and cardiovascular risk factors
Obesity is renowned for the bad company it keeps. A variety of traditional and novel cardiovascular risk factors occur with greater prevalence in obese than in lean persons and are particularly likely to cluster in those with central obesity [27–43]. As previously noted, systemic hypertension occurs more commonly in obese persons than in lean individuals. Diabetes mellitus occurs with significantly higher frequency in obese than in lean persons.
The presence of excessive visceral fat predisposes to increased lipolysis and free fatty acid production. This is thought to decrease glucose utilization and increase glucose production, leading to glucose intolerance [28]. Hyperinsulinemia results and contributes to insulin resistance, which in turn increases free fatty acid production, decreases high-density lipoprotein production, and decreases low-density lipoprotein particle size [28, 37, 38]. Triglyceride elevation frequently accompanies these metabolic alterations. Central obesity in association with systemic hypertension, insulin resistance (with or without glucose intolerance), and atherogenic dyslipidemia comprises the metabolic syndrome, itself a powerful risk factor for coronary artery disease [28, 37–40]. A variety of thrombogenic factors have been associated with central obesity including elevated plasma fibrinogen levels, impaired fibrinolysis, increased factor VII and VIIc activity, and increased plasminogen activator inhibitor levels [41–43]. Plasma homocysteine concentrations are higher in centrally obese than in lean patients [28]. Lipoprotein(a) may also be elevated in obesity [28]. Plasma leptin, which correlates positively with fat mass, was recently identified as an independent cardiovascular risk factor [44]. Obesity has been associated with endothelial dysfunction, an early stage of coronary atherosclerosis.

Effect of weight reduction
Although weight reduction may favorably modify such cardiovascular risk factors as systemic hypertension, diabetes mellitus, and dyslipidemia, there is currently no evidence showing that weight loss, in the absence of risk factor modification, alters coronary heart disease risk [45, 46].

Summary
Obesity produces a variety of alterations in cardiac function and morphology. In the severely obese, these changes, in association with altered pulmonary function, may predispose to congestive heart failure (obesity cardiomyopathy). Many of these abnormalities are reversible with substantial weight loss. The preponderance of evidence suggests that there is an association between coronary heart disease and obesity, particularly central obesity. This association is due in large part to the association of obesity with a variety of traditional and novel cardiovascular risk factors. There is substantial evidence that obesity also serves as an independent risk factor for coronary atherosclerosis.

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Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome.

Alpert MA.

Division of Cardiology, University of South Alabama, College of Medicine, Mobile 36617, USA.

Obesity produces an increase in total blood volume and cardiac output because of the high metabolic activity of excessive fat. In moderate to severe cases of obesity, this may lead to left ventricular dilation, increased left ventricular wall stress, compensatory (eccentric) left ventricular hypertrophy, and left ventricular diastolic dysfunction. Left ventricular systolic dysfunction may occur if wall stress remains high because of inadequate hypertrophy. Right ventricular structure and function may be similarly affected by the aforementioned morphologic and hemodynamic alterations and by pulmonary hypertension related to the sleep apnea/ obesity hypoventilation syndrome. The term obesity cardiomyopathy is applied when these cardiac structural and hemodynamic changes result in congestive heart failure. Obesity cardiomyopathy typically occurs in persons with severe and long-standing obesity. The predominant causes of death in those with obesity cardiomyopathy are progressive congestive heart failure and sudden cardiac death.

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Obesity and cardiac function.

de Divitiis O, Fazio S, Petitto M, Maddalena G, Contaldo F, Mancini M.

We studied 10 obese volunteers, mean age 36.5 +/- 10.3 years, who weighed 123.56 +/- 28.7 g and were 69.96 +/- 22.5 kg overweight. The subjects did not have diabetes, arterial hypertension or signs of cardiac and respiratory failure or disease and all underwent right- and left-heart catheterization. cardiac output and stroke volume were high, according to increased oxygen consumption and to the degree of obesity. Ventricular end-diastolic and atrial pressures ranged from normal to high and correlated with body weight, signs of volume overloading and reduced left ventricular (LV) compliance. The mean pulmonary artery pressure was elevated and correlated well with weight, pulmonary resistance being normal; mean aortic pressure did not correlate with weight, and systemic arterial resistance tended to have a negative correlation. The LV function curve showed impaired ventricular function, particularly for the heaviest subjects, in whom Vmax and the ratio of the stroke work index to LV end-diastolic pressure were reduced. These indexes correlated well with each other and both correlated negatively with the degree of obesity. In contrast, maximal dP/dt was normal and did not correlate with excess weight. These observations show that depressed LV function is already present in relatively young obese people, even if they are free from signs of cardiopathy and other associate diseases. The degree of impairment of heart function seems to parallel the degree of obesity.

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Cardiovascular function in extreme obesity.

Backman L, Freyschuss U, Hallberg D, Melcher A.

PMID: 4717325 [PubMed - indexed for MEDLINE]
 
9: Am J Cardiol 1992 Oct 1;70(9):921-4 Related Articles,

Cardiomyopathy of obesity: a clinicopathologic evaluation of 43 obese patients with heart failure.

Kasper EK, Hruban RH, Baughman KL.

Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, Maryland.

Right heart hemodynamic and endomyocardial biopsy abnormalities associated with marked obesity were characterized in 43 obese patients who presented with symptoms of congestive heart failure. Marked obesity was defined as a body mass index greater than or equal to 35 kg/m2. They were compared to a group of 409 patients with similar presentations but normal body mass. Analysis of the 519 patients showed that body mass index was positively correlated with right heart pressures and cardiac output (p less than or equal to 0.0001), pulmonary vascular resistance index (p less than or equal to 0.003) and systolic blood pressure (p less than or equal to 0.0006). Obese patients had elevated right heart pressures, cardiac output (p less than or equal to 0.0001) and pulmonary vascular resistance index (p less than or equal to 0.02) when compared with a group of lean patients with a similar degree of cardiomyopathy. After evaluation, a significantly higher percentage of obese patients were found to have idiopathic dilated cardiomyopathy compared with lean patients. A specific etiology was found in 264 (64.5%) of the 409 lean patients compared with 10 (23.3%) of the obese patients (p less than or equal to 0.0001). The most common finding on endomyocardial biopsy in the obese group was mild myocyte hypertrophy (67%). These data suggest that the cardiomyopathy of obesity exists and may play an important role in a population referred for the evaluation of heart failure.

PMID: 1529947 [PubMed - indexed for MEDLINE]
 
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Obesity and essential hypertension. Hemodynamics, intravascular volume, sodium excretion, and plasma renin activity.

Messerli FH, Christie B, DeCarvalho JG, Aristimuno GG, Suarez DH, Dreslinski GR, Frohlich ED.

Systemic hemodynamics, intravascular volume, and plasma renin activity were determined in 135 lean, midly obese, or distinctly overweight subjects who were normotensive or had borderline or established essential hypertension. Cardiac output (but not index) was higher and peripheral resistance lower in obese than in lean subjects, except in borderline hypertension. Intravascular volume was increased in obese patients, and more so when corrected for body height; correction for body weight led to relative volume contraction. Intravascular volume correlated directly with cardiac output in the entire population, as well as in the subgroups. Intravascular volume correlated inversely with total peripheral resistance in all subjects and in each subgroup. Both correlations remained significant when an approximation was used to correct influences of obesity on total blood volume. Sodium excretion was higher in obese than in lean subjects. Thus, despite the expanded intravascular volume in obesity, the pathophysiologic relationship between systemic hemodynamics and intravascular volumes remains unchanged. Relatively low peripheral resistance in obesity may decrease the risk of systemic vascular disease. Nevertheless, since circulating volume is increased, the greater venous return adds an additional load to a left ventricle that is already burdened by a high afterload caused by arterial hypertension.

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Role of circulatory congestion in the cardiorespiratory failure of obesity.

Kaltman AJ, Goldring RM.

The role of circulatory congestion in the cardiorespiratory dysfunction of massive obesity was investigated in 18 patients. They were hypervolemic and had increased cardiac outputs proportionate to their weight. The average resting left ventricular filling pressure was within the upper limits of normal, but it increased to abnormally high levels with increased venous return of passive leg raising, and further during exercise. The elevations in pressure were associated with high resting central blood volumes which increased significantly with exertion. These findings are consistent with reduced distensibility of the central circulation in these congested patients. Weight reduction was accompanied by a decrease in central blood volumes and restoration of a normal left ventricular response in three of four patients and a return toward normal in one. The improvement in ventricular function with relief of edema and dyspnea. In 14 patients with normal or only minimal alveolar hypoventilation, there were no significant transpulmonary diastolic pressure gradients despite a marked increase in left ventricular end-diastolic pressures. One patient, after regaining weight, subsequently had an abnormal gas exchange and an increased pulmonary vascular resistance. He and two others with severe alveolar hypoventilation demonstrated cor pulmonale on a background of left ventricular dysfunction and congestion of the circulation. Two other patients, the least obese of the group, had hypoventilation and cor pulmonale with normal left ventricular pressures. Hypervolemia and a hyperdynamic state are common features of the obese patients. High cardiac output is maintained despite marked circulatory congestion which may result in generalized anasarca and increased ventricular filling pressures. This clinical syndrome may be present in obese patients without intrinsic heart disease and may be reversible with weight reduction. The central circulatory congestion may contribute to the development of the alveolar hypoventilation syndrome in certain obese patients.

PMID: 1020753 [PubMed - indexed for MEDLINE]

12. Alpert MA, Alexander JK. Cardiac morphology and obesity in man. In: Alpert MA, Alexander JK, eds. The Heart and Lung in Obesity. Armonk, NY: Futura; 1998:25–44.

13: Int J Obes Relat Metab Disord 1995 Aug;19(8):550-7 Related Articles,

Interrelationship of left ventricular mass, systolic function and diastolic filling in normotensive morbidly obese patients.

Alpert MA, Lambert CR, Terry BE, Cohen MV, Mukerji V, Massey CV, Hashimi MW, Panayiotou H.

Division of Cardiology, University of South Alabama College of Medicine, Mobile 36617, USA.

OBJECTIVE: To determine the interrelationship of left ventricular (LV) mass, systolic function and diastolic relaxation in morbidly obese subjects. METHOD: We obtained echocardiograms (M-mode, two dimension) and cardiac Doppler studies (pulse wave, continuous wave colour flow) on 50 subjects whose actual body weight was > or = twice ideal body weight. LV mass/height index was calculated from echocardiographic data (Penn Convention). LV systolic function was assessed by calculating LV fractional shortening. LV diastolic filling was assessed by measuring the transmitral Doppler E/A ratio and the transmitral E wave deceleration time. RESULTS: There were significant positive correlations between LV mass/height index and the LV internal dimensions in diastole, systolic blood pressure, LV end-systolic wall wall stress and the transmitral E wave deceleration time. There were significant negative correlations between LV mass/height index and both LV fractional shortening and the transmitral Doppler E/A ratio. There were significant negative correlations between LV fractional shortening and the LV internal dimension in diastole, systolic blood pressure LV end-systolic wall stress and the transmitral E wave deceleration time. There was a significant positive correlation between LV fractional shortening and the transmitral Doppler E/A ratio. There were significant positive correlations between the transmitral E wave deceleration time and LV internal dimension in diastole, systolic blood pressure and LV end-systolic wall stress. There were significant negative correlations between the transmitral Doppler E/A ratio and the aforementioned variables. CONCLUSIONS: Unfavourable alterations in LV loading conditions contribute to the development of LV hypertrophy and impairment systolic dysfunction in morbidly obese subjects. Increasing LV mass and altered loading conditions may synergistically contribute to impairment of LV diastolic filling in such individuals.

PMID: 7489025 [PubMed - indexed for MEDLINE]
 
14: JAMA 1991 Jul 10;266(2):231-6 Related Articles,

The impact of obesity on left ventricular mass and geometry. The Framingham Heart Study.

Lauer MS, Anderson KM, Kannel WB, Levy D.

Charles A. Dana Research Institute, Boston, Mass.

OBJECTIVE.--To determine the relationship of varying degrees of obesity with left ventricular mass and geometry. DESIGN.--Survey. SETTING.--Population-based epidemiologic study. PARTICIPANTS AND METHODS.--M-mode echocardiograms, which were adequate for estimation of left ventricular mass, were obtained in 3922 healthy participants of the Framingham Heart Study. Measured height and weight were used to calculate body-mass index, a measure of obesity. RESULTS.--Body-mass index was strongly correlated with left ventricular mass. After adjusting for age and blood pressure, body-mass index remained a strong independent predictor of left ventricular mass, left ventricular wall thickness, and left ventricular internal dimension (P less than .01 for all). Body-mass index was associated with prevalence of echocardiographic left ventricular hypertrophy, particularly in subjects with a body-mass index exceeding 30 kg/m2. CONCLUSIONS.--Obesity is significantly correlated with left ventricular mass, even after controlling for age and blood pressure. The increase in left ventricular mass associated with increasing adiposity reflects increases in both left ventricular wall thickness and left ventricular internal dimension.

PMID: 1829117 [PubMed - indexed for MEDLINE]
 
15: Am J Cardiol 1995 Dec 1;76(16):1194-7 Related Articles,
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Relation of duration of morbid obesity to left ventricular mass, systolic function, and diastolic filling, and effect of weight loss.

Alpert MA, Lambert CR, Panayiotou H, Terry BE, Cohen MV, Massey CV, Hashimi MW, Mukerji V.

Division of Cardiology, University of South Alabama College of Medicine, Mobile, Alabama 36617, USA.

Longer duration of morbid obesity is associated with higher LV mass, poorer LV systolic function, and greater impairment of LV diastolic filling. Weight loss-induced decreases in LV mass and improvements in LV systolic function and diastolic filling are due in part to favorable alterations in LV loading conditions.

PMID: 7484912 [PubMed - indexed for MEDLINE]

16. Alpert MA, Alexander JK. Obesity and ventricular function in man: systolic function. In: Alpert MA, Alexander JK, eds. The Heart and Lung in Obesity. Armonk, NY: Futura; 1998:77–94.

17: Am J Cardiol 1993 Mar 15;71(8):733-7 Related Articles,

Factors influencing left ventricular systolic function in nonhypertensive morbidly obese patients, and effect of weight loss induced by gastroplasty.

Alpert MA, Terry BE, Lambert CR, Kelly DL, Panayiotou H, Mukerji V, Massey CV, Cohen MV.

Division of Cardiology, University of South Alabama College of Medicine, Mobile.

Heart rate and blood pressure were measured, and echocardiography was performed in 39 patients whose actual body weight was greater than twice their ideal body weight to identify factors influencing left ventricular (LV) systolic function in morbidly obese patients and assess the effect of weight loss on LV systolic function. Patients were studied before and after weight loss induced by gastroplasty. The study cohort was 133 +/- 8% overweight before weight loss and 39 +/- 7% overweight at the nadir of weight loss. Before weight loss, LV fractional shortening varied inversely with LV internal dimension in diastole (an indirect index of preload), LV end-systolic wall stress and systolic blood pressure (indexes of afterload). The weight loss-induced change in LV fractional shortening varied directly with the pre-weight loss LV internal dimension in diastole, LV end-systolic wall stress and systolic blood pressure, and inversely with the pre-weight loss LV fractional shortening. The weight loss-induced change in LV fractional shortening varied inversely with the weight loss-induced changes in LV end-systolic stress and systolic blood pressure. In patients with reduced LV fractional shortening (n = 14), weight loss produced a significant increase in LV fractional shortening that was accompanied by a significant decrease in LV internal dimension in diastole, LV end-systolic stress and systolic blood pressure. The results suggest that LV loading conditions have an important role in determining LV systolic function in morbidly obese patients. Improvement in LV systolic function in these patients is closely related to weight loss-induced alterations in LV loading conditions.

PMID: 8447274 [PubMed - indexed for MEDLINE]

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19: Am J Med Sci 2001 Apr;321(4):237-41 Related Articles,

Management of obesity cardiomyopathy.

Alpert MA.

Division of Cardiology, University of South Alabama, College of Medicine, Mobile 36617, USA.

Therapy of acute exacerbations of congestive heart failure associated with obesity cardiomyopathy consists of dietary salt restriction, inspired oxygen, diuretics, and angiotensin-converting enzyme inhibitors or, if left ventricular systolic dysfunction is present, hydralazine/isosorbide dinitrate. Digitalis may be indicated in selected cases. These measures may also be useful chronically in association with weight loss. Substantial weight loss is capable of reversing all of the hemodynamic abnormalities associated with obesity except elevation of left ventricular filling pressure. Substantial weight loss may also reduce left ventricular mass and improve left ventricular diastolic filling in those with left ventricular hypertrophy before weight loss. Left ventricular systolic function also improves after weight loss in those with impaired pre-weight-loss systolic function. These beneficial effects of weight loss occur partly because of favorable alterations in left ventricular loading conditions. Substantial weight loss in patients with congestive heart failure associated with obesity cardiomyopathy produces a reversal of many of the clinical manifestations of cardiac decompensation and improves New York Heart Association functional class in most patients.

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PMID: 11307865 [PubMed - indexed for MEDLINE]

 
20: Surgery 1990 Oct;108(4):809-18; discussion 818-20 Related Articles,

Assessment of cardiac function in patients who were morbidly obese.

Alaud-din A, Meterissian S, Lisbona R, MacLean LD, Forse RA.

Department of Surgery, Royal Victoria Hospital, McGill University, Montreal, Canada.

Cardiac function of 30 patients who were morbidly obese was studied before bariatric surgery. Twelve patients were studied 13 +/- 4 months after surgery. These patients had a mean age of 37.1 +/- 2.9 years and a body mass index of 50.0 +/- 1.4 kg/m2. Cardiac function was measured by echocardiography, radionuclide angiography scanning, and right heart catheterization. To determine the degree of cardiac dysfunction, the patients were studied with exercise and intravenous fluid challenges. Ultrasonography produced evidence of myocardial thickening with an increased interventricular septum in eight patients (32%) and increased left ventricular mass in 17 patients (53%). The radionuclide scan suggested that morbid obesity was associated with a significantly (p less than 0.05) increased end-diastolic volume and decreased left ventricular ejection fraction as compared with patients who were of normal weight. With exercise the patient who was of normal weight had an increase in the end-diastolic volume, stroke volume, and heart rate, but the patient who was morbidly obese only increased heart rate to produce the necessary increase in cardiac output. Right heart catheterization indicated that the relationship of the pulmonary wedge pressure and the left ventricular stroke work index was abnormal in 14 of 29 patients (48.3%) and depressed in six of 29 patients (20.7%) with exercise. One liter of fluid caused an abnormal relationship of the pulmonary wedge pressure and the left ventricular stroke work index in 12 of 30 patients (40%) and a depressed response in 10 of 30 patients (33.3%). Cardiac studies were repeated in 12 patients after a 54.8 +/- 1.9 kg weight loss. Echocardiography indicated a decrease in dilatation (27.3% to 9.1%) and a significant (p less than 0.05) decrease in hypertrophy (45.5% to 0%). After the weight loss, radionuclide and right heart catheterization studies indicated improved cardiac function with reduced filling pressures and increased left ventricular work during fluid and exercise challenges. These results support the presence of obesity-related cardiomyopathy with ventricular dysfunction, which appears to be caused by a noncompliant ventricle. Significant weight loss achieved with gastroplasty results in increased ventricular compliance and improved cardiac function.

PMID: 2218895 [PubMed - indexed for MEDLINE]
 
21: Circulation 1972 Feb;45(2):310-8 Related Articles,

Cardiovascular effects of weight reduction.

Alexander JK, Peterson KL.

PMID: 4257897 [PubMed - indexed for MEDLINE]

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26. Alpert MA, Terry BE, Lambert CR, et al. Cardiac morphology and left ventricular function in morbidly obese patients with and without congestive heart failure, and effect of weight loss. Am J Cardiol. 1997;80:736–740.

27: Acta Med Scand 1979;205(5):367-73 Related Articles,

Reversibility of cardiovascular changes in extreme obesity. Effects of weight reduction through jejunoileostomy.

Backman L, Freyschuss U, Hallberg D, Melcher A.

PMID: 443075 [PubMed - indexed for MEDLINE]

28. Alexander JK. Obesity and coronary heart disease. In: Alpert MA, Alexander JK, eds. The Heart and Lung in Obesity. Armonk, NY: Futura; 1998:213–238.

29: Ann Intern Med 1985 Dec;103(6 ( Pt 2)):1010-9 Related Articles,

Obesity, atherosclerosis, and coronary artery disease.

Barrett-Connor EL.

Although several risk factors for heart disease including high blood pressure, diabetes mellitus, and lipid and lipoprotein abnormalities are associated with overweight, overweight is not consistently associated with coronary heart disease risk. Some prospective studies of white men (life insurance cohorts, airline pilots, cancer study volunteers, and the Framingham population) have shown a positive linear relationship of weight to coronary heart disease. Other epidemiologic studies show a negative association, no association, a U-shaped relationship, or a threshold effect. The inconsistencies do not appear to be explained by differences in the definition or distribution of obesity, duration of follow-up, or risk factor distribution. Neither misclassification bias nor confounding by cigarette smoking or chronic disease appears to explain the inconsistencies. No known protective effect of obesity could explain these divergent findings. Inconsistent results with regard to the nature, strength, and linearity of the association between obesity and atherosclerosis do not support the hypothesis that obesity causes atherosclerosis, despite its biological plausibility.

Publication Types:
  • Review


PMID: 3904565 [PubMed - indexed for MEDLINE]

 
30: Am J Epidemiol 1991 Jul 15;134(2):111-22 Related Articles,

Comment in:


Predictors of arteriographically defined coronary stenosis in the Honolulu Heart Program. Comparisons of cohort and arteriography series analyses.

Reed D, Yano K.

Honolulu Heart Program National Heart, Lung, and Blood Institute, Bethesda, MD.

The purpose of this study was to determine if the major risk factors for clinical myocardial infarction also predicted coronary artery stenosis as defined by arteriography. Of a cohort of 7,591 men who were free of cardiovascular disease at entry, 357 had arteriographic studies during a 20-year follow-up period. Risk factor levels were therefore known prior to the onset of clinical symptoms and arteriographic studies. Men with arteriograms were divided into groups with and without prior clinical myocardial infarction. High blood pressure, serum cholesterol, obesity, and low alcohol intake predicted both severe coronary stenosis and incident myocardial infarction, thus indicating that these variables were associated with clinical events through the underlying process of atherosclerosis. Dietary intake of cholesterol and serum glucose also had similar but not always statistically significant patterns of association with both coronary stenosis and myocardial infarction. In contrast, serum triglyceride and cigarette smoking predicted clinical myocardial infarction, but not severe coronary stenosis. This suggests that these variables play a stronger role in the precipitation of acute clinical events than in the underlying process of atherosclerosis. The findings were quite different for several risk factors when analyzed in a case-control format using the arteriography series from this same data set. Examination of possible explanations for the differences raises questions concerning the use of arteriography series for etiologic studies of coronary atherosclerosis.

PMID: 1862795 [PubMed - indexed for MEDLINE]

 
31: Arterioscler Thromb 1992 Dec;12(12):1387-92 Related Articles,

Upper-body fat distribution: a hyperinsulinemia-independent predictor of coronary heart disease mortality. The Paris Prospective Study.

Casassus P, Fontbonne A, Thibult N, Ducimetiere P, Richard JL, Claude JR, Warnet JM, Rosselin G, Eschwege E.

INSERM Unite 21, Villejuif, France.

The Paris Prospective Study is a long-term investigation of the factors predicting coronary heart disease in a large population of middle-aged men. The first follow-up examination involved 7,152 subjects, who were natives of metropolitan France and were free of any cardiovascular history. At that time, the usual cardiovascular risk factors and plasma insulin levels were recorded. An index of body fat distribution, the iliac-to-thigh ratio, was entered into the list of predictive variables, despite the fact that it had been measured 1 year before the first follow-up examination. After 11 years of mean follow-up, 129 of the men had died of coronary heart disease. Univariate analysis showed that the iliac-to-thigh ratio (p < 0.0001) and plasma insulin level (both fasting [p < 0.003] and 2-hour postload [p < 0.02]), as well as the four major risk factors of coronary heart disease (age, smoking, blood pressure, and plasma cholesterol level) were significantly higher in subjects who died of coronary heart disease compared with those who had died of another cause or were alive at the end of follow-up. In multivariate stepwise logistic regression, the iliac-to-thigh ratio appeared as an independent predictor of coronary heart disease death, thereby causing the removal of fasting insulin level from the list of significant independent predictors. Nevertheless, in a model that entered 2-hour postload insulin in two classes (high or low), both the insulin level and iliac-to-thigh ratio were found as significant independent predictors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 1450171 [PubMed - indexed for MEDLINE]
 
32: Circulation 1983 May;67(5):968-77 Related Articles,

Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study.

Hubert HB, Feinleib M, McNamara PM, Castelli WP.

The relationship between the degree of obesity and the incidence of cardiovascular disease (CVD) was reexamined in the 5209 men and women of the original Framingham cohort. Recent observations of disease occurrence over 26 years indicate that obesity, measured by Metropolitan Relative Weight, was a significant independent predictor of CVD, particularly among women. Multiple logistic regression analyses showed that Metropolitan Relative Weight, or percentage of desirable weight, on initial examination predicted 26-year incidence of coronary disease (both angina and coronary disease other than angina), coronary death and congestive heart failure in men independent of age, cholesterol, systolic blood pressure, cigarettes, left ventricular hypertrophy and glucose intolerance. Relative weight in women was also positively and independently associated with coronary disease, stroke, congestive failure, and coronary and CVD death. These data further show that weight gain after the young adult years conveyed an increased risk of CVD in both sexes that could not be attributed either to the initial weight or the levels of the risk factors that may have resulted from weight gain. Intervention in obesity, in addition to the well established risk factors, appears to be an advisable goal in the primary prevention of CVD.

PMID: 6219830 [PubMed - indexed for MEDLINE]
 
33: J Chronic Dis 1977 Sep;30(9):567-84 Related Articles,

Change in risk factor and the development of chronic disease. A methodological illustration.

Hsu PH, Mathewson FA, Abu-Zeid HA, Rabkin SW.

PMID: 903389 [PubMed - indexed for MEDLINE]
 
34: Br Med J (Clin Res Ed) 1984 May 12;288(6428):1401-4 Related Articles,

Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913.

Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Bjorntorp P, Tibblin G.

In a prospective study of risk factors for ischaemic heart disease 792 54 year old men selected by year of birth (1913) and residence in Gothenburg agreed to attend for questioning and a battery of anthropometric and other measurements in 1967. Thirteen years later these baseline findings were reviewed in relation to the numbers of men who had subsequently suffered a stroke, ischaemic heart disease, or death from all causes. Neither quintiles nor deciles of initial indices of obesity (body mass index, sum of three skinfold thickness measurements, waist or hip circumference) showed a significant correlation with any of the three end points studied. Statistically significant associations were, however, found between the waist to hip circumference ratio and the occurrence of stroke (p = 0.002) and ischaemic heart disease (p = 0.04). When the confounding effect of body mass index or the sum of three skinfold thicknesses was accounted for the waist to hip circumference ratio was significantly associated with all three end points. This ratio, however, was not an independent long term predictor of these end points when smoking, systolic blood pressure, and serum cholesterol concentration were taken into account. These results indicate that in middle aged men the distribution of fat deposits may be a better predictor of cardiovascular disease and death than the degree of adiposity.

PMID: 6426576 [PubMed - indexed for MEDLINE]

35. Yater WM, Traum AH, Spring S, et al. Coronary artery disease in men eighteen to thirty-nine years of age. Am Heart J. 1948;36:334–372.
36. Lee KT, Thomas WA. Relationship of body weight to acute myocardial infarction. Am Heart J. 1956;52:581–591.

37: Int J Obes 1991 Sep;15 Suppl 2:109-15 Related Articles,

Insulin resistance in visceral obesity.

Kissebah AH.

Medical College of Wisconsin, Froedtert Memorial Lutheran Hospital, Milwaukee 53226.

Publication Types:
  • Review
  • Review, Tutorial


PMID: 1794931 [PubMed - indexed for MEDLINE]

 
38: N Engl J Med 1996 Apr 11;334(15):952-7 Related Articles,

Comment in:

Click here to read 
Hyperinsulinemia as an independent risk factor for ischemic heart disease.

Despres JP, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ.

Lipid Research Center, Laval University Hospital Research Center, Quebec, Canada.

BACKGROUND. Prospective studies suggest that hyperinsulinemia may be an important risk factor for ischemic heart disease. However, it has not been determined whether plasma insulin levels are independently related to ischemic heart disease after adjustment for other risk factors, including plasma lipoprotein levels. METHODS. In 1985 we collected blood samples from 2103 men from suburbs of Quebec City, Canada, who were 45 to 76 years of age and who did not have ischemic heart disease. A first ischemic event (angina pectoris, acute myocardial infarction or death from coronary heart disease) occurred in 114 men (case patients) between 1985 and 1990. Each case patient was matched for age, body-mass index, smoking habits, and alcohol consumption with a control selected from among the 1989 men who remained free of ischemic heart disease during follow-up. After excluding men with diabetes, we compared fasting plasma insulin and lipoprotein concentrations at base line in 91 case patients and 105 controls. RESULTS. Fasting insulin concentrations at base line were 18 percent higher in the case patients than in the controls (P<0.001). Logistic-regression analysis showed that the insulin concentration remained associated with ischemic heart disease (odds ratio for ischemic heart disease with each increase of 1 SD in the insulin concentration, 1.7; 95 percent confidence interval, 1.3 to 2.4) after adjustment for systolic blood pressure, use of medications, and family history of ischemic heart disease. Further adjustment by multivariate analysis for plasma triglyceride, apolipoprotein B, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations did not significantly diminish the association between the insulin concentration and the risk of ischemic heart disease (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.3). CONCLUSIONS. High fasting insulin concentrations appear to be an independent predictor of ischemic heart disease in men.

PMID: 8596596 [PubMed - indexed for MEDLINE]

 
39: Arteriosclerosis 1990 Jul-Aug;10(4):497-511 Related Articles,

Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease.

Despres JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C.

Physical Activity Sciences Laboratory, Laval University, Ste-Foy, Quebec, Canada.

Several epidemiological studies have reported that the regional distribution of body fat is a significant and independent risk factor for cardiovascular disease (CVD) and related mortality. Although these associations are well established, the causal mechanisms are not fully understood. Numerous studies have, however, shown that specific topographic features of adipose tissue are associated with metabolic complications that are considered as risk factors for CVD such as insulin resistance, hyperinsulinemia, glucose intolerance and type II diabetes mellitus, hypertension, and changes in the concentration of plasma lipids and lipoproteins. The present article summarizes the evidence on the metabolic correlates of body fat distribution. Potential mechanisms for the association between body fat distribution, metabolic complications, and CVD are reviewed, with an emphasis on plasma lipoprotein levels and plasma lipid transport. From the evidence available, it seems likely that subjects with visceral obesity represent the subgroup of obese individuals with the highest risk for CVD. Although body fat distribution is now considered as a more significant risk factor for CVD and related death rate than obesity per se, further research is clearly needed to identify the determinants of body fat distribution and the causal mechanisms involved in the metabolic alterations. It appears certain, however, that an altered plasma lipid transport is a significant component of the relation between body fat distribution and CVD.

Publication Types:
  • Review
  • Review, Tutorial


PMID: 2196040 [PubMed - indexed for MEDLINE]

 
40: J Clin Invest 1996 Jun 1;97(11):2601-10 Related Articles,
Click here to read 
Obesity/insulin resistance is associated with endothelial dysfunction. Implications for the syndrome of insulin resistance.

Steinberg HO, Chaker H, Leaming R, Johnson A, Brechtel G, Baron AD.

Department of Medicine, Indiana University Medical Center, Indianapolis, Indiana 46202, USA.

To test the hypothesis that obesity/insulin resistance impairs both endothelium-dependent vasodilation and insulin-mediated augmentation of endothelium-dependent vasodilation, we studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of methacholine chloride (MCh) or sodium nitroprusside (SNP) during saline infusion and euglycemic hyperinsulinemia in lean insulin-sensitive controls (C), in obese insulin-resistant subjects (OB), and in subjects with non-insulin-dependent diabetes mellitus (NIDDM). MCh induced increments in LBF were approximately 40% and 55% lower in OB and NIDDM, respectively, as compared with C (P < 0.05). Euglycemic hyperinsulinemia augmented the LBF response to MCh by - 50% in C (P < 0.05 vs saline) but not in OB and NIDDM. SNP caused comparable increments in LBF in all groups. Regression analysis revealed a significant inverse correlation between the maximal LBF change in response to MCh and body fat content. Thus, obesity/insulin resistance is associated with (a) blunted endothelium-dependent, but normal endothelium-independent vasodilation and (b) failure of euglycemic hyperinsulinemia to augment endothelium-dependent vasodilation. Therefore, obese/insulin-resistant subjects are characterized by endothelial dysfunction and endothelial resistance to insulin's effect on enhancement of endothelium-dependent vasodilation. This endothelial dysfunction could contribute to the increased risk of atherosclerosis in obese insulin-resistant subjects.

PMID: 8647954 [PubMed - indexed for MEDLINE]
 
41: Arterioscler Thromb Vasc Biol 1996 Mar;16(3):368-74 Related Articles,
Click here to read 
Visceral fat accumulation and its relation to plasma hemostatic factors in healthy men.

Cigolini M, Targher G, Bergamo Andreis IA, Tonoli M, Agostino G, De Sandre G.

Institute of Clinical Medicine, University of Verona, Italy.

The associations between abdominal visceral fat and the plasma hemostatic system were examined in 38-year-old healthy men (n=52) with a wide range of fatness and fat distribution. Plasma hemostatic factors and metabolic parameters, including glucose tolerance, were measured, and body fatness and adipose tissue distribution were assessed by using computed tomography. The men with more visceral fat (ie, higher than the median value [n=26]) had a less favorable metabolic profile than the men with less visceral fat (n=26). They also had significantly (P<.05) higher plasma fibrinogen, factor VIII clotting activity, tissue-type plasminogen activator antigen, and plasminogen activator inhibitor-1 (PAI-1) activity (19.2+/-2.4 versus 8.5+/-1.6 AU/mL, P<.001) and lower basal tissue-type plasminogen activator activity. After adjustment for plasma insulin, the men with larger abdominal visceral fat area still had significantly higher plasma PAI-1 activity, but no difference was found in any of the other hemostatic factors. In multiple linear regression analysis, abdominal visceral fat area was a positive predictor of plasma PAI-1 activity, but it failed to show any significant association with other hemostatic factors after controlling for plasma insulin. These results suggest the presence of relationships between abdominal visceral fat and several plasma hemostatic factors that are largely mediated by concomitant alterations in plasma insulin concentration. In addition, our results suggest that abdominal accumulation of visceral fat is an independent predictor of plasma PAI-1 activity.

PMID: 8630661 [PubMed - indexed for MEDLINE]

42. Anellone G, DiGarbo V, Cardova R, et al. Blood coagulation and fibrinolysis in obese NIDDM patients. Diabetes Res. 1994;25:85–92.

43: Arterioscler Thromb 1993 Feb;13(2):162-9 Related Articles,

Impact of weight loss on plasminogen activator inhibitor (PAI-1), factor VII, and other hemostatic factors in moderately overweight adults.

Folsom AR, Qamhieh HT, Wing RR, Jeffery RW, Stinson VL, Kuller LH, Wu KK.

Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454-1015.

Based on previous cross-sectional findings, we hypothesized that weight loss could improve several hemostatic factors associated with cardiovascular disease. In a randomized controlled trial, moderately overweight men and women were assigned to one of four weight loss treatment groups or to a control group. Measurements of plasminogen activator inhibitor-1 (PAI-1) antigen, tissue-type plasminogen activator (t-PA) antigen, D-dimer antigen, factor VII activity, fibrinogen, and protein C antigens were made at baseline and after 6 months in 90 men and 88 women. Net treatment weight loss was 9.4 kg in men and 7.4 kg in women. There was no net change (p > 0.05) in D-dimer, fibrinogen, or protein C with weight loss. Significant (p < 0.05) decreases were observed in the combined treatment groups compared with the control group for mean PAI-1 (31% decline), t-PA antigen (24% decline), and factor VII (11% decline). Decreases in these hemostatic variables were correlated with the amount of weight lost and the degree that plasma triglycerides declined; these correlations were stronger in men than women. These findings suggest that weight loss can improve abnormalities in hemostatic factors associated with obesity.

Publication Types:
  • Clinical Trial
  • Randomized Controlled Trial


PMID: 8427853 [PubMed - indexed for MEDLINE]

 
44: Circulation 2001 Dec 18;104(25):3052-6 Related Articles,

Comment in:

Click here to read 
Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS).

Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A, Sattar N.

Department of Pathological Biochemistry, Glasgow Royal Infirmary, University of Glasgow, Glasgow, Scotland.

BACKGROUND: Leptin plays a role in fat metabolism and correlates with insulin resistance and other markers of the metabolic syndrome, independent of total adiposity. Therefore, we hypothesized that raised leptin levels may identify men at increased risk of a coronary event in the West of Scotland Coronary Prevention Study (WOSCOPS). Methods and Results- Plasma leptin levels were measured at baseline in 377 men (cases) who subsequently experienced a coronary event and in 783 men (controls) who remained free of an event during the 5-year follow-up period of the study. Controls were matched to cases on the basis of age and smoking history and were representative of the entire WOSCOPS cohort. Leptin levels were significantly higher in cases than controls (5.87+/-2.04 ng/mL versus 5.04+/-2.09 ng/mL, P<0.001). In univariate analysis, for each 1 SD increase in leptin, the relative risk (RR) of an event increased by 1.25 (95% confidence interval [CI], 1.10 to 1.43; P<0.001). There was minimal change in this RR with correction for body mass index (RR, 1.24; 95% CI, 1.06 to 1.45; P=0.006) or with further correction for classic risk factors, including age, lipids, and systolic blood pressure (RR, 1.20; 95% CI, 1.02 to 1.42; P=0.03). Leptin correlated with C-reactive protein (r=0.24, P<0.001) and, even with this variable added to the model, leptin retained significance as a predictor of coronary events (RR, 1.18; 95% CI, 1.00 to 1.39; P=0.05) at the expense of C-reactive protein. CONCLUSIONS: We show, for the first time, in a large prospective study that leptin is a novel, independent risk factor for coronary heart disease.

PMID: 11748099 [PubMed - indexed for MEDLINE]

 
45: Int J Obes 1991 Dec;15(12):853-9 Related Articles,

Improvement of glucose and lipid metabolism associated with selective reduction of intra-abdominal visceral fat in premenopausal women with visceral fat obesity.

Fujioka S, Matsuzawa Y, Tokunaga K, Kawamoto T, Kobatake T, Keno Y, Kotani K, Yoshida S, Tarui S.

Second Department of Internal Medicine, Osaka University Medical School, Japan.

Visceral fat obesity (VFO) with predominant intra-abdominal fat accumulation has been shown to be more often associated with metabolic disorders than subcutaneous fat obesity (SFO). In the present study, changes in fat distribution and their effects on metabolic complications were investigated in forty premenopausal female obese patients in whom substantial weight reduction was obtained by means of a low calorie diet. Analysis of fat distribution by CT scanning demonstrated that visceral fat decreased to a greater extent than abdominal subcutaneous fat, which was particularly evident in VFO patients. On the other hand, change of fat distribution was small in SFO patients. That is, visceral to subcutaneous abdominal fat ratio (V/S ratio) decreased from 0.62 +/- 0.36 to 0.46 +/- 0.33 in VFO, whereas from 0.23 +/- 0.07 to 0.20 +/- 0.09 in SFO after weight reduction. Although obese patients, especially those with VFO, were frequently associated with glucose intolerance and hyperlipidemia, marked diminution was observed in the elevated levels of plasma glucose area on 75g OGTT, serum total cholesterol and triglyceride after weight reduction. By the examination of interrelationship between the changes in body weight, BMI, total and regional fat volume and changes in glucose and lipid metabolism, we found that the decrease in the V/S ratio and visceral fat volume were more strongly correlated with the improvement in plasma glucose and lipid metabolism compared to the decrease in body weight, BMI, total fat volume and abdominal subcutaneous fat volume. Furthermore, partial correlation analyses demonstrated that the metabolic improvements were associated with changes in visceral abdominal fat after control for changes in total adipose tissue volume.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 1794928 [PubMed - indexed for MEDLINE]
 
46: Am J Clin Nutr 1996 Feb;63(2):225-33 Related Articles,

Effects of diet and exercise on common cardiovascular disease risk factors in moderately obese older women.

Fox AA, Thompson JL, Butterfield GE, Gylfadottir U, Moynihan S, Spiller G.

Aging Study Unit, Geriatrics Research, Education, and Clinical Center, Veterans Affairs Health Care System, Palo Alto, CA 94304, USA.

Diet and exercise studies of premenopausal women have shown reductions in obesity and other cardiovascular disease (CVD) risk factors. Forty-one healthy, moderately obese (120-140% of ideal body weight, LBW), postmenopausal women (65.6 +/- 3.3 y) participating in 24-wk diet or diet + exercise programs were studied to determine whether similar CVD risk reduction would occur. Daily energy need (DEN) was estimated from basal energy expenditure and self-reported activity. The diet + exercise group (n = 16) reduced their daily energy intake (DEI) by 2092 kJ from their DEN and expended 837 kJ/d in walking and resistance exercise. The two diet-only groups (n = 13 and n = 12) reduced their DEI by 2092 and 2929 kJ from their DEN, respectively. Body weight, waist-to-hip and subscapula-to-triceps ratios, blood lipids (total, low-density-lipoprotein, and high-density-lipoprotein cholesterol, and triacylglycerols), glucose, and insulin concentrations were measured at baseline and after 12 and 24 wk of diet and diet + exercise. Data were analyzed by using analysis of variance with repeated measures (P < or = 0.05) and Tukey's post hoc test. Loss of body weight was significant for all groups between baseline and 12 and 24 wk (baseline: 79.3 +/- 7.6 kg; 12 wk; 75.1 +/- 7.7 kg; 24 wk; 72.8 +/- 8.0 kg) but did not differ among groups. No significant time or treatment effects were observed between baseline and 24 wk for changes in mean blood lipid, glucose, and fasting insulin concentrations or measures of body fat distribution. Although 24 wk of diet or diet+exercise significantly reduced body weight in this group, this loss in body weight was not accompanied by a reduction of other commonly accepted CVD risks.

Publication Types:
  • Clinical Trial
  • Controlled Clinical Trial


PMID: 8561064 [PubMed - indexed for MEDLINE]

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