Hypertension in Africa: Redressing the burden of cardiovascular disease using cost-effective nonpharmacological approaches

Hypertension may affect approximately one fifth or more of all adult South Africans. Despite the considerable evidence derived from economically developed countries to indicate the extent to which hypertension contributes to cardiovascular disease (CVD), it is only more recently that data has emerged from the African continent to support a contention that hypertension is the principal risk factor for CVD in African populations and that CVD accounts for a major proportion of deaths in the elderly and in younger adults in rural Africa. Active engagement in the harsh realities of managing this complex clinical trait should therefore be foremost on the minds of the healthcare sector in Africa. In this regard there are unique challenges. In the present personal review we synthesise the evidence for or against the view that at a public health level, the answer to significantly reducing the burden of CVD produced by hypertension in African populations, may lie in something as simple as generating a healthier lifestyle. In this regard, we place recent evidence obtained from South African studies of the importance of modifiable cardiovascular risk factors related to hypertension, including salt intake and obesity, in the context of previously published evidence. We highlight the very recent and the first substantive evidence derived from an African community to show that salt intake indeed contributes to a significant portion of blood pressure (BP) variability in African populations, but this effect may be hidden because the impact is largely on central (aortic) rather than brachial BP. We also discuss the increasing evidence to show that in African populations, the adverse effects of the epidemic of obesity that faces emerging communities is likely to account for a substantial proportion of cardiovascular risk not through marked effects on brachial BP, but through indirect effects by promoting the adverse effects of BP on the heart. In the present review we therefore argue that despite limited absolute effects of salt intake and obesity on brachial BP, a marked benefit could be gained by the BP effects of salt restriction and body weight reduction in African communities

Impact of dietary-induced obesity on adrenergic-induced cardiomyocyte damage in rats

Although obesity is an independent risk factor for heart failure and even mild-to-moderate forms of obesity are associated with myocardial systolic dysfunction the mechanisms of the myocardial dysfunction have not been identifi ed. We assessed whether dietary-induced obesity is associated with an increased sensitivity of the myocardium to ß-adrenergic-induced cardiomyocyte apoptosis or fibrosis. To induce obesity, rats were fed a diet that promotes an increased caloric intake. Adrenergic-induced cardiomyocyte apoptosis was determined by injecting rats for 5 days with isoproterenol (0.01 mg/kg/day for 3 days and 0.02 mg/kg/day for 2 days) and then studying the degree of cardiomyocyte damage using a TUNEL assay and assessing the pathological score. Five months of feeding rats a diet that promoted the development of an increased body weight (Control=481±4.3 g, Diet=550±7.8 g, p‹0.001) and visceral fat content (Control=19.6±0.8 g, Diet=33.0±1.2 g, p‹0.0001), did not alter baseline cardiomyocyte apoptosis. However, 5 days of ß-adrenergic activation resulted in an enhanced cardiomyocyte apoptosis in rats receiving the experimental diet as compared to rats receiving a normal diet (p‹0.01). No changes in the myocardial pathological score (fibrosis) were noted. The enhanced adrenergic-induced cardiomyocyte apoptosis in obese rats could not be explained by dietary-induced increases in baseline left ventricular internal diameters, decreases in systolic function (endocardial or midwall fractional shortening) or differences in the response of the heart to adrenergic-induced increases in inotropic or chronotropic function. In conclusion, the present study suggests that obesity may contribute to myocardial dysfunction by increasing the sensitivity of the myocardium to adrenergic-induced cardiomyocyte damage

The relationship between the nitric oxide synthase gene and the risk of hypertension defi ned according to ambulatory blood pressures

Although nitric oxide (NO) plays an important role in blood pressure (BP) control, whether variation of genes involved in regulating the synthesis of NO infl uences BP is uncertain. As the heritability of BP is stronger for ambulatory than it is for conventional BP, we assessed the independent association of the well described functional exon 7 Glu298Asp variant of the eNOS gene with the presence of hypertension in 511 randomly selected normotensive control participants and 503 hypertensives with a diagnosis of hypertension confi rmed with 24-hour ambulatory BP profiles whilst off therapy. We also assessed the relationship between eNOS genotype and 24 hour ambulatory BP. Comparisons of genotype and allele frequencies indicated a lack of association of the exon 7 Glu298Asp gene variant with hypertension (Odds ratio of genotype predicting the presence of hypertension=0.97, confidence interval=0.70-1.30, p=0.92). However, patients with the Glu/Glu genotype of the Glu298Asp variant (n=424) had increased 24-hour systolic and diastolic blood pressures (152±1/97±1 mm Hg) in comparison to patients heterozygous for the Glu298Asp variant or homozygous for the 298Asp allele (n=79) (145±1/94±1 mm Hg, p‹0.005 for systolic BP and p‹0.001 for diastolic BP after multiple adjustments including age, gender, body mass index and the presence of diabetes mellitus). Differences in systolic and diastolic BP between genotype groups were noted during the day as well as at night. The association of eNOS genotype with ambulatory BP translated into an increased risk of more severe grades of hypertension in patients with the Glu/Glu genotype (grade II and III vs. grade I, Odds ratio=2.20, confidence interval=1.34-3.59, p‹0.0002). In conclusion, a functional gene variant (Glu298Asp) at the eNOS locus contributes ~1.4-2.5% to the variation in ambulatory blood pressure within hypertensives, but is not associated with the presence of hypertension in patients in whom the diagnosis has been confirmed by 24-hour ambulatory BP values. The relationship between eNOS genotype and 24-hour ambulatory BP and the severity of hypertension warrants further study

Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure

ObjectivesThe purpose of this research was to evaluate the therapeutic value of initiating a beta-blocker before an angiotensin-converting enzyme inhibitor (ACEI) in the treatment of heart failure.BackgroundAlthough ACEI and carvedilol produce benefits in heart failure, whether the order of initiation of therapy determines the impact on left ventricular (LV) function and New York Heart Association functional class (NYHA FC) has not been determined.MethodsA single-center, prospective, randomized, open-label study was performed. We evaluated whether initiation of therapy with carvedilol either before (n = 38) or after (n = 40) perindopril therapy in newly diagnosed patients in NYHA FC II to III heart failure with idiopathic dilated cardiomyopathy, with the addition of the alternative agent after six months, determined subsequent changes in NYHA FC and LV function (echocardiography and radionuclide ventriculography). Study drugs were titrated to maximum tolerable doses.ResultsThere were no differences in baseline characteristics between the study groups. After 12 months 11 patients died (6 in the group where the ACEI was initiated). At 12 months the group receiving carvedilol as initial therapy achieved a higher tolerable dose of carvedilol (43 ± 17 mg vs. 33 ± 18 mg, p = 0.03); a lower dose of furosemide (p < 0.05); and better improvements in symptoms (NYHA FC, p < 0.002), LV ejection fraction (radionuclide: 15 ± 16% vs. 6 ± 13%, p < 0.05; echocardiographic, p < 0.01), and plasma N-terminal pro-brain natriuretic peptide concentrations (p < 0.02).ConclusionsAs opposed to the conventional sequence of drug use in the treatment of heart failure, initiation of therapy with carvedilol before an ACEI results in higher tolerable doses of carvedilol and better improvements in FC and LV function

The Impact of Different Classification Criteria Sets on the Estimated Prevalence and Associated Risk Factors of Diastolic Dysfunction in Rheumatoid Arthritis

This study compared the estimated prevalence and potential determinants of left ventricular (LV) diastolic dysfunction upon applying different classification criteria in rheumatoid arthritis (RA). LV diastolic function was assessed echocardiographically by pulsed Doppler (E/A), tissue Doppler (E/e′, lateral and septal e′), and left atrial volume index in 176 RA patients. Relationships of traditional cardiovascular risk factors and RA characteristics with LV diastolic function and dysfunction according to previous and current criteria were determined in multivariate regression models. Waist-hip ratio was associated with E/A (standardised β (SE) = -0.28±0.09, p=0.0002) and lateral e′ (standardised β (SE) = 0.26±0.09, p=0.01); low diastolic blood pressure was related to E/e′ (standardised β (SE) = -0.16±0.08, p=0.04). Diastolic dysfunction prevalence differed upon applying previous (59%) compared to current (22%) criteria (p<0.0001). One SD increase in waist-hip ratio was associated with diastolic dysfunction when applying current criteria (OR = 2.61 (95% CI = 1.51–4.52), p=0.0006), whereas one SD increase in diastolic blood pressure was inversely related to diastolic dysfunction upon using previous criteria (OR = 0.57 (95% CI = 0.40–0.81), p=0.002). In conclusion, application of current and previous diastolic dysfunction criteria markedly alters the prevalence and risk factors associated with diastolic dysfunction in RA