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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Hypertension. Author manuscript; available in PMC 2010 December 1.
Published in final edited form as:
PMCID: PMC2803034


Experimental and clinical studies show that chronic hypertension leads to myocardial pathology and systolic and diastolic dysfunction that frequently progresses to heart failure1. Elevated afterload causes cardiomyocyte hypertrophy, which alters myocardial energy metabolism by increasing glucose metabolism and impairing mitochondrial oxidative capacity, increasing production of reactive oxygen species and oxidative damage, and triggering remodeling of the myocardial extracellular matrix and left ventricle (see Figure)2. Obesity is also a strong risk factor for both hypertension and heart failure, and has been increasing at epidemic proportions worldwide3, 4. The increase in obesity in Western societies over the last century is associated with greater consumption of highly processed carbohydrate (e.g. sugar, white flour, white potatoes) and saturated fats5. At present, there is little information regarding the effects of dietary fat and carbohydrate composition on cardiac function and the development of heart failure in hypertension.

Figure 1
Schematic depiction of the potential impact of a “junk food” diet on the development of cardiac pathology essential hypertension. A diet high in sugar, high glycemic starch and saturated fats promotes myocardial dysfunction through hypertension ...

In this issue of the journal, Majane et al. present the novel finding that consuming a diet that is high in sugar and saturated fat results in relative modest obesity (~10% increase in body mass) compared to a sugar free-low fat diet, but greatly accelerates left ventricular dysfunction in a rat model of essential hypertension6. Importantly, this effect occurred in the absence of an increase in blood pressure and with no signs of diabetes or systemic insulin resistance. Cardiac dysfunction was associated with two classic indicators of myocardial pathology that occur in response to hypertension: accelerated cardiomyocyte apoptosis and activation of matrix metalloproteinase-2. These important findings support the concept that in essential hypertension, a high saturated fat/high sugar diet accelerates the progression from modest left ventricular concentric hypertrophy to frank pump dysfunction.

The effects of glycemic load and fat intake on the development of myocardial pathology and contractile dysfunction in patients with hypertension have not been reported. There is, however, a growing shift in the paradigm for the role of dietary macronutrient composition in the incidences of coronary heart disease (CHD)7. Recent epidemiological studies found no reduction in CHD associated with consumption of a low fat/high carbohydrate diet, and reduced risk with consumption of a diet that is low in sugar and rapidly absorbed starches and high in polyunsaturated fatty acids7, 8. It is becoming increasing clear that consuming a diet with a high glycemic load typical of the “junk food” diet, is strongly associated with an increased risk for CHD8.

Other recent reports from rodent models of chronic arterial pressure overload suggest that in the absence of severe obesity, a low carbohydrate/high fat diet attenuates development of left ventricular hypertrophy and heart failure, while a high sugar diet accelerate this process9, 10. The cardiac effects of dietary lipids and carbohydrates in hypertension are complex and poorly defined, and the optimal diet for prevention of cardiac dysfunction and heart failure in hypertension is not known. It is important to separate the adverse effects of dietary intake of sugar, refined starches and saturated fat on the heart from the established detrimental impact of obesity on the cardiovascular system3, 4, 9. In our recent work in the Dahl hypertensive rat we observed less left ventricular dysfunction and chamber expansion with a high fat/low carbohydrate diet compared to a high starch or high sugar diet in the absence of any differences in fat or body mass, thus suggesting a direct pathological link between dietary glycemic index and cardiac pathology in hypertension9, 10. This suggest that the pathology observed by Majane et al. may be due to the high intake of sugar and saturated fat, and not the relatively modest level of obesity that was induced by the diet. Adverse effects of a high sugar diet can clearly occur without obesity, 9, 11. The mechanism behind this observation may be generation of NADPH and reactive oxygen species by accelerated flux of glucose into the oxidative pentose phosphate pathway12, as suggested by the observation that treatment with the anti-oxidant tempol prevented cardiac hypertrophy, left ventricular remodeling, contractile dysfunction, and myocardial lipid peroxidation in fructose-fed mice subjected to aortic constriction11. Alternatively, it could be the result of flux through the hexosamine biosynthetic pathway or greater N-acetyl-glucosamine production9.

We propose that prolonged intake of a typical ‘’junk food’’ diet triggers multiple steps that eventually converge to accelerate the onset of heart failure (see Figure). Excess caloric intake results in obesity that is closely linked to myocardial structural and functional changes, e.g. increased left ventricular mass that frequently results in heart failure4. In support, a large community-based study found that obesity is an independent risk factor for the onset of heart failure3. There is also a robust relationship between obesity and the development of hypertension, i.e. increased sympathetic activity likely plays a crucial role in obesity-induced hypertension and could raise arterial pressure by causing peripheral vasoconstriction and by increasing renal tubular sodium retention13. Hypertension itself is also an independent risk factor for the onset of contractile dysfunction and heart failure1. We further propose that excessive intake of high glycemic foods and saturated fats perturbs normal myocardial metabolism and signaling, activating pathological processes (see Figure). For example, a high glycemic load enhances myocardial glucose uptake by increasing insulin and lowering plasma free fatty acids, which may stimulate flux through the hexosamine and pentose pathways, and generation of reactive oxygen species and oxidative damage9, 11. In addition, high intake of saturated fatty acids coupled with the suppressed rate of mitochondrial fatty acid oxidation in hypertrophied and failing myocardium should facilitate accumulation generation of ceramides, which could result in cardiomyocyte apoptosis2, 9. For example, we found a higher rate of cardiomyocyte apoptosis in healthy rats fed a high fat diet comprised of saturated fatty acids compared to a diet rich in mono- and polyunsaturated fats, which correlated with lower cardiac palmitoylceramide levels14. Together, a vicious cycle may thus be established where continued consumption of a high glycemic/high saturated fat diet by hypertensive individuals further exacerbates pathological processes in the myocardium, causing systolic and diastolic dysfunction, and triggering the progression to heart failure (see Figure).

In summary, the results of the study by Majane et al. support the concept that high intake of sugar and saturated fat accelerates development of cardiac pathology and pump dysfunction in hypertension despite no signs of diabetes and only a modest level of obesity6. Thus the combination of poor macronutrient intake and hypertension appears to form a potent ‘’cocktail’’ that severely impairs cardiac function. These findings raise the interesting possibility that dietary manipulation may represent a relatively cost-effective and easy adjunctive therapeutic option that could be offered to hypertensive and heart failure patients. However, additional clinical and basic studies are required to further test this hypothesis and to delineate underlying mechanisms that link high ‘’junk food’’ intake to reduced contractile and diastolic function.

Supplementary Material



Sources of Funding:

W.C. Stanley and M.F. Essop were supported by a National Institutes of Health Fogarty International Research Collaboration Award (R03-TW007344).



William C. Stanley: NONE

Keyur B. Shah: NONE

M. Faadiel Essop: NONE

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