Heart and Metabolism

Echocardiographic and hemodynamic data in obese patients

H. Schunkert
Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg,
Regensburg, Germany
Correspondence: Prof. Dr. med. Heribert Schunkert, Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Tel: +49 941 9447233, fax: +49 941 9447235, e-mail: heribert.schunkert@klinik.uni-regensburg.de

Abstract
Obesity entails a wide variety of adaptations in the cardiovascular system. Specifically, high body mass index results in an increase in heart rate and blood volume, as well as in systolic and diastolic hypertension. Not surprisingly, these changes affect cardiac geometry and mass. In addition to anthropometric factors, neurohormonal and inflammatory systems may be activated, resulting in further cardiac and vascular remodeling. In synergy, these maladaptive changes in the obese organism increase the risk of coronary heart disease and congestive heart failure. This review focuses on the hemodynamic mechanisms involved in these processes.
- Heart Metab. 2002;17:14–19.

Keywords: Obesity, left ventricular hypertrophy, cardiac remodeling, fat mass, hypertension

Hemodynamic adaptations to obesity
Cardiac alterations in patients with obesity reflect an integrated response to multiple hemodynamic, metabolic, and inflammatory derangements. Most notably, the risk of arterial hypertension increases dramatically with obesity. For example, in the Augsburg MONICA survey, the prevalence of arterial hypertension in middle-aged lean subjects was 19%. This number increased to 55% in those with a body mass index (BMI) above 30 kg/m2 irrespective of age and gender. Regarding the incidence of hypertension the Framingham Heart Study documented that a weight gain of 5% increases the risk of hypertension by 30% within a 4-year period [1]. Not surprisingly, average systolic and diastolic blood pressures display marked differences according to categories of BMI (Figure 1).

Figure 1. Systolic and diastolic blood pressures and the prevalence of hypertension in 1670 individuals in the Augsburg MONICA surveys. Data are adjusted for age and gender. With increasing BMI, a substantial increase was observed for each parameter, documenting the profound effects of obesity on cardiac afterload.

In addition to blood pressure, the viscosity of the blood determines cardiac afterload. In this respect, obese individuals present with elevated hematocrit as well as elevated fibrinogen levels (Figure 2) [2]. In concert, these changes alter the rheological properties, adding further to the pressure load on the hearts of obese individuals [2]. In addition to pressure overload, volume load of the heart is elevated in obese individuals. In fact, cardiac output increases in parallel with body weight, suggesting an adaptive response of the heart to serve the increased circulatory demands [3]. Cardiac output in the MONICA population showed a highly significant increase with increasing categories of BMI (Figure 3). Finally, individuals with obesity present with higher heart rates, a finding that probably reflects increased sympathetic drive (Figure 3) [4].
Taken together, the heart of an obese person is faced by a series of maladaptive mechanisms that synergistically increase pressure and volume load as well as heart rate. Structural changes to the cardiac muscle are an inevitable consequence.

Figure 2. Hematocrit and fibrinogen levels in 1670 individuals in the Augsburg MONICA surveys. Both key determinants of blood viscosity increase with obesity, adding to the pressure load of the heart.

Changes in cardiac mass and geometry
In light of the hemodynamic changes, it is no surprise that obesity alters left ventricular (LV) mass and geometry. Most significantly, obesity results in an increased risk of left ventricular hypertrophy (LVH) [5]. Even after adjustment for age, gender, and blood pressure, the Framingham Heart Study demonstrated highly significant relations between BMI and LV dimensions and wall thicknesses [6, 7]. The probability of LVH rises from 5.5% in lean subjects to 29.9% in obese subjects (Figure 4). Indeed, obesity may confer a higher risk for LVH than arterial hypertension [8].

Figure 3. Cardiac output and heart rate in 1134 individuals in the Augsburg MONICA surveys. The data document that the volume and chronotropic demands on the heart increase in parallel with BMI.

Echocardiographic analyses have provided further evidence of the adaptive changes in cardiac geometry in obese individuals. Particularly, echocardiography allows the investigator to establish whether the pathological increase in LV mass is due to dilatation of the heart (eccentric LVH) or due to thickening of its walls (concentric LVH). In obesity, LVH is caused to a variable extent by increases in LV volume and LV wall thickness [8–10]. Indeed, obesity in the absence of hypertension was found to predominantly increase volume load. Subsequently, LV dimensions increase and so thus the risk of eccentric LVH. By contrast, obesity in conjunction with hypertension resulted predominantly in increased LV wall thickness [11].

Figure 4. Prevalence of LVH in 1670 individuals in the Augsburg MONICA surveys. With increasing BMI, a substantial increase in LVH was observed, documenting the profound risk related to obesity with respect to cardiac hypertrophy.

Coexistence of obesity and hypertension
Obesity is considered to be the most frequently occurring secondary form of arterial hypertension. Thus, both conditions may often be found in combination. With respect to cardiac geometry, Kuch and coworkers analyzed the combined effects of obesity and hypertension [10]. Most notably, the coexistence of hypertension and obesity produced a concentric pattern of LVH. Accordingly, in obese, hypertensive individuals the predominant cardiac effects were seen in the form of increased posterior and septal thicknesses. The additive effects of obesity and hypertension with respect to the most important hemodynamic and cardiac structural parameters are summarized in Figure 5 [11].

Figure 5. Flow chart showing the hemodynamic, structural, and functional alterations of the heart observed in obese patients (adapted from [8]).

Differentiation between fat and fat-free mass
In order to elucidate the mechanisms that form the link between obesity and cardiac structural changes it may be of interest to take a closer look at body composition. Roughly, body composition may be divided into fat and fat-free mass. With respect to the heart, this distinction is of particular interest since fat mass is poorly perfused whereas fat-free mass determines the circulatory demands. Obesity not only results in an increase in fat mass but also an increase in fat-free mass in an average ratio of 8:2 [12]. However, there may be substantial interindividual variability with respect to body composition in obese subjects. Therefore, the Strong Heart and Augsburg MONICA studies used body impedance measurements in order to distinguish between poorly perfused fat mass and metabolically active fat-free mass [9, 13]. LV dimensions were found to be strongly associated with fat-free mass, whereas septal and posterior wall thicknesses correlated with fat mass. These data suggest that differential mechanisms may contribute to the increase in LV dimension and wall thickness in obese individuals.
The disproportional increase in LV wall thickness, as observed with elevated fat mass, mimics the effects of arterial hypertension. By contrast, an increase in fat-free body mass (visceral organs, musculature) increases the circulatory demands and may result in a balanced increase in cardiac size. Thus, with respect to the heart, the pathological component of obesity is largely the increase in fat mass that results in pressure overload and, subsequently, concentric remodeling of the myocardium.

Cardiac function and obesity
LVH has been identified as one of the strongest predictors of heart failure [14]. Thus, the changes in cardiac morphology and geometry of obese individuals are only intermediate steps towards a profound alteration in cardiac function (Figure 5). Most prominently, the chronic elevation of cardiac pressure load and secondary concentric LVH result in a progressive impairment of LV filling, leading to a high risk of diastolic heart failure. Accordingly, obesity has been identified as an independent predictor of LV diastolic dysfunction in the general population [15].
With excessive obesity, alterations in systolic function may also become evident. In particular, longstanding obesity may result in a decrease in mid-wall fiber shortening and ejection fraction [16]. In conjunction, diastolic and systolic malfunction of the heart, along with obesity itself, contributes to the symptomatology of obese individuals, most notably dyspnea and reduced exercise capacity.
In addition to changes in cardiac function, cardiac arrhythmias are frequently found in obese subjects [17]. Particularly if there is a concentric pattern of LVH, the prevalence of ventricular ectopic beats is substantially raised. Moreover, obesity is a significant risk factor for atrial fibrillation [18]. In this respect the hyperdynamic circulation in conjunction with diastolic dysfunction, as observed in obesity, may constitute important pathophysiological mechanisms that cause atrial enlargement and, subsequently, fibrillation. In addition to the respective symptoms, these arrhythmias may also contribute to the elevated cardiovascular risk observed in obese individuals (Figure 5).

Regression of hypertension and LVH by weight reduction
Numerous interventional studies have documented that weight reduction reduces the risk of arterial hypertension and LVH in obese individuals. In fact, in some studies, weight reduction was more successful than pharmacological therapy with respect to LVH regression and blood pressure lowering [19]. Undoubtedly, weight reduction helps to limit hypotensive pharmacotherapy in obese individuals. Moreover, sympathetic drive and heart rate variability may be substantially improved by weight loss [20]. It is unclear at present whether weight reduction also has beneficial effects on long-term disturbances of systolic and diastolic cardiac function in obesity. However, there is no doubt that the clinical symptoms of heart failure such as dyspnea and reduced exercise capacity respond well to weight reduction. In addition, preliminary evidence suggests that pharmacologically assisted weight reduction has beneficial effects on cardiac geometry and function [21].

Conclusion
The heart of an obese individual is subjected to a multitude of hemodynamic, neuroendocrine, and metabolic factors that, in conjunction, lead to volume and pressure load on the heart. Depending on the admixture of contributing factors, either eccentric or concentric LVH develops as an intermediate step. Ultimately, symptoms of heart failure or
cardiac arrhythmias develop, increasing the risk of cardiac death. Emphasis should therefore be focused on weight reduction and prevention of cardiac alterations secondary to obesity.

Acknowledgments
Supported by grants of the Deutsche Forschungsgemeinschaft; the Bundes-
ministerium für Forschung und Technologie; the Vaillant Stiftung, Munich; the Deutsche Stiftung für Herzforschung, Frankfurt; the Ernst and Berta Grimmke Stiftung; and an
unrestricted research grant from R.W. Johnson Pharmaceutical Research, Raritan, NJ.

REFERENCES

1: Lancet 2001 Nov 17;358(9294):1682-6

Related Articles,

Comment in:

Lancet. 2001 Nov 17;358(9294):1659.

Assessment of frequency of progression to hypertension in non-hypertensive participants in the Framingham Heart Study: a cohort study.

Vasan RS, Larson MG, Leip EP, Kannel WB, Levy D.

From the National Heart, Lung, & Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA. vasan@fram.nhlbi.nih.gov

BACKGROUND: Patients with optimum (<120/80 mm Hg), normal (120-129/80-84 mm Hg), and high normal (130-139/85-89 mm Hg) blood pressure (BP) may progress to hypertension (>140/90 mm Hg) over time. We aimed to establish the best frequency of BP screening by assessing the rates and determinants of progression to hypertension. METHODS: We assessed repeated BP measurements in individuals without hypertension (BP<140/90 mm Hg) from the Framingham Study (4200 men, 5645 women; mean age 52 years) who attended clinic examinations during 1978-94. The incidence of hypertension (or use of antihypertensive treatment) and its determinants were studied. FINDINGS: A stepwise increase in hypertension incidence occurred across the three non-hypertensive BP categories; 5.3% (95% CI 4.4-6.3%) of participants with optimum BP, 17.6% (15.2-20.3%) with normal, and 37.3% (33.3-41.5%) with high normal BP aged below age 65 years progressed to hypertension over 4 years. Corresponding 4-year rates of progression for patients 65 years and older were 16.0% (12.0-20.9), 25.5% (20.4-31.4), and 49.5% (42.6-56.4), respectively. Obesity and weight gain also contributed to progression; a 5% weight gain on follow-up was associated with 20-30% increased odds of hypertension. INTERPRETATION: High normal BP and normal BP frequently progress to hypertension over a period of 4 years, especially in older adults. These findings support recommendations for monitoring individuals with high normal BP once a year, and monitoring those with normal BP every 2 years, and they emphasise the importance of weight control as a measure for primary prevention of hypertension.

PMID: 11728544 [PubMed - indexed for MEDLINE]

2: Thromb Res 1994 Aug 1;75(3):223-31