Pathophysiologically based antihypertensive pharmacotherapeutics rationality, efficacy and safety in Sub Saharan African Nations - A review.

BACKGROUND: Hypertension (HT) prevalence, Uncontrolled Blood Pressure (UBP), morbidity and mortality are highest in Sub-Saharan Africa (SSA). Correlating pathophysiology of HT to pharmaco-therapy with antihypertensive drugs (AHD) may bring amelioration. Aims:To review peculiarities of HT in SSA, UBP causes, diagnostic modalities, AHD use, rationality and efficacy. METHODS AND RESULTS: 14 published therapeutic audits in 4 SSA nations on Google Scholar or PUBMED, (total n = 6496 patients) were evaluated. Calcium Channel blockers (CCB) amlodipine, and thiazide diuretics (TD), hydrochlorothiazide (HCTZ) were the commonest AHD. Thiazide Like Diuretics (TLD) were underutilized. The % of patients on AHD were: 1 drug 5.4-55%; 2 drugs 37-82%; >/ = 3 drugs 6-50.3%. 2-drug combinations were: ACEI/ARB + TD (42%); CCB + TD (36.8%); ACEI + CCB (15.8%) of studies. Triple/quadruple therapy included Methyldopa (MTD) with ACEI + CCB or TD. The (%) attaining BP < 140/< 90 mmHg, ranged from 29 to 53.6%, median, 44%. The co-morbidities, range and median were: Diabetes Mellitus (DM): 9.8-64%, 19.2%; Chronic Kidney Disease (CKD): 5.7-7.5%, 6.9%, and Coronary artery Disease (CAD): 0.9-2.6%, 2.3%. ACEI + CCB ± TD were the preferred AHD for comorbidities. CONCLUSIONS: Therapeutic inertia; Non-compliance; co-morbidities; refractory HT; ignorance; substandard AHD; contribute to UBP. Studies relating 24 hour ABPM to complications and mortality in SSA hypertensives; and impact of different AHD classes on ABPM, are needed. Study of ACEI + alpha-1 blockers + TLD on 24 hour ABPM and personalized care, are required.

Right ventricular systolic function in hypertensive heart failure.

BACKGROUND: Heart failure (HF) is a major cause of cardiovascular admissions and hypertensive heart failure (HHF) is the most common cause of HF admissions in sub-Saharan Africa, Nigeria inclusive. Right ventricular (RV) dysfunction is being increasingly recognized in HF and found to be an independent predictor of adverse outcomes in HF. This study aimed to determine the prevalence of RV systolic dysfunction in HHF by several echocardiographic parameters. METHODOLOGY: One hundred subjects with HHF were recruited consecutively into the study along with 50 age and sex-matched controls. All study participants gave written informed consent, and had a full physical examination, blood investigations, 12-lead electrocardiogram, and transthoracic echocardiography. RV systolic function was assessed in all subjects using different methods based on the American Society of Echocardiography guidelines for echocardiographic assessment of the right heart in adults. This included tricuspid annular plane systolic excursion (TAPSE), RV myocardial performance index (MPI), and RV systolic excursion velocity by tissue Doppler (S'). RESULTS: RV systolic dysfunction was found in 53% of subjects with HHF by TAPSE, 56% by RV MPI, and 48% by tissue Doppler systolic excursion S'. RV systolic dysfunction increased with reducing left ventricular ejection fraction (LVEF) in subjects with HHF. CONCLUSION: A high proportion of subjects with HHF were found to have RV systolic functional abnormalities using TAPSE, RV MPI, and RV S'. Prevalence of RV systolic dysfunction increased with reducing LVEF.

Normal Limits of Electrocardiogram and Cut-Off Values for Left Ventricular Hypertrophy in Young Adult Nigerians.

This study assessed healthy young adults to determine the normal limits for electrocardiographic variables and cut-off values for left ventricular hypertrophy. It was a cross sectional descriptive study in which the participants were evaluated clinically by standard 12-lead resting electrocardiogram (ECG) at 25 mm/s during quiet respiration. The heart rate, P wave duration, axis and amplitude, PR and QT intervals, QRS duration, axis and amplitude and T wave axis were assessed. Three hundred and twenty four (324) volunteers comprising of 175 males and 149 females aged 20 to 30 years (mean, 23.01 ± 2.88 years) participated in the study. The normal limits for heart rate, P wave duration, amplitude and axis in lead II, QRS duration and axis, T wave axis, PR interval, QT interval and QTc respectively were; 61-93 beats per minute,0.08-0.12s,1.00-2.00 mm,22.00-79.000,78.00-106.00 ms,15.50-81.000, 24.25-69.000,0.12-0.19s, 0.32-0.40s and 0.36-0.44s. The cut-off values for Sokolow-Lyon, Cornell and Araoye criteria for assessment of left ventricular hypertrophy (LVH) were higher than those previously in use in medical practice. Gender difference exists in some cut-off values for LVH. This study defined the normal limits for electrocardiographic variables for young adult Nigerians. Racial factor should be taken into consideration in interpretation of ECG.

Cardiovascular responses to treadmill exercise in Nigerian hypertensives with left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is an independent risk factor for adverse cardiac outcomes in hypertensive patients. OBJECTIVE: This study is designed to assess the cardiovascular responses to treadmill exercise among Nigerian hypertensives with echocardiographically proven LVH. MATERIALS AND METHODS: Fifty hypertensive patients with LVH (27 males and 23 females) between 30 and 65 years of age were studied in Nigeria. 50 hypertensive patients without LVH and 50 normal subjects who were age and sex matched served as controls. All patients and control subjects underwent M-mode, 2-D and Doppler ECHO-studies and the Bruce protocol treadmill exercise test. RESULTS: The study showed that the estimated maximal oxygen consumption (MVO2) in MET reduced progressively from 8.39 ± 1.26 (normotensive control) to 7.62 ± 1.33 (hypertensive without LVH), 6.27 ± 0.99 (hypertensive with LVH) (P<0.0001ANOVA). The duration of exercise (s) was also reduced in that order from 455.4 ± 79.1 to 411.6 ±8 2.3, 315.8 ± 75.6 respectively (P<0.0001). The systolic blood pressure (SBP) and pressure rate product (PRP) during maximal exercise were also increased in hypertensives with LVH and hypertensive without LVH when compared to normotensive controls. The hypertensives with LVH and hypertensives without LVH also showed significant limitation to heart rate increase with exercise compared to normotensive controls (P<0.003). CONCLUSION: This study demonstrated significant impairment of exercise capacity in hypertensives with or without LVH compared to normotensive subjects. Both earlier recognition and improved understanding of LVH may lead to more effective therapeutic strategies for this cardiovascular risk factor.

Ambulatory blood pressure profile and left ventricular geometry in Nigerian hypertensives.

BACKGROUND: Left ventricular hypertrophy (LVH) is an independent cardiac risk factor in hypertensives and the structural classification of left ventricular (LV) geometry provides additional prognostic information. Ambulatory blood pressure (ABP) monitoring has been shown to be superior to office blood pressure (BP) in relation to hypertension LVH. We investigated ambulatory BP variables in relation to LV geometric patterns in Nigerian hypertensives. MATERIALS AND METHODS: A total of 130 patients (males = 96, females = 34) with hypertension had their 24-hours ambulatory BP and trans-thoracic 2D/M- mode echocardiography. Data were analyzed with SPSS 13.0. P < 0.05 was considered statistically significant. RESULTS: The mean age of the patients was 54.08±11.88 years. The prevalence rate of abnormal LV geometry was 48.4%. Mean ambulatory Systolic BP (day time, night time and 24-hour-average) was significantly higher in patients with LVH compared with those without LVH. Day-night systolic and diastolic BP decay (i.e. percentage nocturnal decline in BP) was also significantly lower in LVH group than in the group without LVH. Patients with eccentric LVH had abnormal day time mean ambulatory systolic BP, night time mean ambulatory systolic BP, elevated day time and night time systolic BP loads, as well as non-dipping diastolic BP pattern. Significant correlates of LV mass index in this study population were mean ambulatory systolic BP (day time: r = 0.355, P = 0.004; night time: r = 0.343, P = 0.005; 24- hour average: r = 0.358, P = 0.004) and day-night decay (systolic: r = -0.388, P = 0.007; diastolic: r = -0.290, P = 0.022) as well as 24-hour systolic BP variability. CONCLUSION: The presence of LVH in hypertension was associated with higher mean ambulatory systolic BP and lower percentage nocturnal decline in systolic and diastolic BP than its absence which appeared to be worse in patients with eccentric LV geometry when compared with other geometric patterns.

The significance of mild renal dysfunction in chronic heart failure.

BACKGROUND: Heart failure is a major public health concern. Prediction models in heart failure have employed echo-cardiography and other advanced laboratory parameters in predicting the risk of mortality. However, most of the patients in the resource poor economies still do not have easy access to these advanced technology. OBJECTIVE: To determine the clinical and echocardiographic correlates of patients with chronic heart failure (CHF) in the presence or mild renal disease (MRD). METHODS: One hundred CHF patients were categorized based on their estimated glomerular filtration rates into either normal renal function or MRD. The clinical and echocardiographic variables of both groups were compared. RESULTS: There were 38 females and 62 males with an overall mean age of 54 years. A significantly greater proportion of patients with mild renal disease presented in New York Heart Association classes 3 and 4 (82.9% vs 27.1%). Patients with MRD had echocardiographic findings of a significantly larger left atrial dimension, lower ejection fraction and fractional shortening and shorter deceleration time. A significantly greater proportion of patients with mild renal disease also had moderate-severe mitral and tricuspid regurgitation and grades 2-3 diastolic dysfunction compared to patients without mild renal disease. Patients with MRD also exhibited a significantly greater degree of deterioration in the fractional shortening and ejection fraction compared to non-MRD patients. Multivariate regression analysis indicated that a low ejection fraction and a low fractional shortening were significantly associated with MRD. CONCLUSION: Identification of MRD in chronic heart failure patients using the estimated glomerular filtration rate is valuable in resource poor countries. The presence of MRD in CHF is associated with poor left ventricular function and increased deterioration of ventricular function.

Blood pressure response to an exercise treadmill test, and echocardiographic left ventricular geometry in Nigerian normotensive diabetics.

OBJECTIVES: This study evaluated normotensive diabetic patients' blood pressure response to graded exercise and their echocardiographic pattern of left ventricular geometry. METHODS: A descriptive, cross-sectional, hospital-based study was carried out on 30 normotensive type 2 diabetic patients and 34 controls, aged 30 to 60 years. The outcome measures were to determine the exercise-related variable, blood pressure response, and left ventricular geometry by means of echocardiography. RESULTS: Nineteen (29.7%) and 11 (17.2%) normotensive diabetic subjects had normal left ventricular geometry and concentric left ventricular remodelling, respectively. None of the subjects had concentric or eccentric left ventricular hypertrophy. On this basis, the normotensive diabetic subjects were divided to two groups: G1 (normal) and G2 (concentric left ventricular remodelling). The groups had comparable mean age, body mass index (BMI), fasting blood glucose (FBG) and two-hour post-prandial blood glucose values, and heart rate, systolic (SBP) and diastolic blood pressure (DBP) at rest. G2 patients had higher mean duration of diabetes than G1 subjects (69.0 +/- 9.48 vs 18.7 +/- 8.7 months; p = 0.007). Peak systolic blood pressure was significantly higher in G2 than G1 subjects (213.6 +/- 20.1 vs 200.0 +/- 15.3 mmHg; p = 0.04). Although there was no statistically significant difference in the left ventricular (LV) mass index between the groups, G2 patients had significantly higher relative wall thicknesses than G1 patients (0.53 +/- 0.03 vs 0.41 +/- 0.04; p < 0.001). CONCLUSION: Normotensive diabetic subjects with concentric left ventricular remodelling have increased blood pressure reactivity to exercise. It is probable, as suggested in earlier studies, that increased blood pressure reactivity to exercise is an indicator of target-organ damage, particularly in normotensive diabetics.

Anthropometric evaluation of cachexia in chronic congestive heart failure: the role of tricuspid regurgitation.

Cardiac cachexia has recently been identified as an independent risk factor for mortality in chronic congestive heart failure. The aims of our study were to further identify the clinical or biochemical predictors or correlates of the cachexia, and to quantitate the magnitude of wasting. We undertook an anthropometric comparison of 30 patients with congestive heart failure, aged 56 (13) years, with ten age- and sex-matched healthy volunteers and 16 patients with essential hypertension. In comparison to the healthy volunteers, the heart failure patients exhibited a trend towards a lower body mass index, 21 (2.7) versus 23 (3.8) kg/m2, the 95% confidence interval for the difference being -0.54 to 5.4. However, the mid-upper arm circumference, of 24 (3.8) cm in the heart failure patients, was significantly (P<0.02) lower than the 27 (2.0) cm in the healthy volunteer group, with a 95% confidence interval for the difference being 1.18 to 4.82 cm. The triceps, mid-thigh, scapula and abdominal skinfold thicknesses were separately and significantly (P<0.05) diminished in the heart failure patients compared to the healthy controls. The sum of the four skin fold thicknesses, with a value of 68 (13) mm in the healthy volunteers, was highly significantly greater (P<0.001) than the value of 35.6 (9) mm in the heart failure patients. The 95% confidence interval for this difference was 22.7 to 41.3 mm. The patients with essential hypertension differed significantly from the heart failure patients in all of these parameters (P<0.01), but were not statistically different from the healthy controls in the anthropometric parameters. Among the heart failure patients, those with tricuspid regurgitation (n = 12) had a worse clinical, biochemical and cachexia profile compared to patients without the tricuspid regurgitation (n = 18). The values (tricuspid regurgitation versus no regurgitation) were New York Heart Association Class, 3.5 (0.65) versus 2.7 (0.75), P<0.01; ejection fraction of 34 (9) versus 43 (13)%, not significant; greater hepatomegaly of 159 (31) versus 135 (29) mm, P<0.05; more severe hypoalbuminemia, 24.5 (2.7) versus 28.5 (6.8) g/l, P<0.05; and worse hyponatremia, 128 (4) versus 133 (5) mmol/l, P<0.05. The tricuspid regurgitation group had a significantly more severe reduction in abdominal and scapula skin fold thickness (P<0.01) than that found in patients without tricuspid regurgitation. The sum of the four skin fold thicknesses was significantly lower (P<0.05) in tricuspid regurgitation, 30.9 (8) mm, than in heart failure without associated regurgitation, 38.0 (9.6). The 95% confidence interval for the difference was 0.8 to 13.4 mm. It is concluded that significant diminution of muscle bulk and subcutaneous fat occurs in chronic heart failure. Tricuspid regurgitation may be an accentuating and accelerating risk factor for cardiac cachexia, on account of a greater hypoalbuminemia and hyponatremia, which, presumably, results from the associated protein-losing enteropathy.

Vasodilator therapy of hypertensive acute left ventricular failure: comparison of captopril-prazosin with hydralazine-isosorbide dinitrate.

A prospective study to evaluate and compare the cardiorespiratory effects and clinical efficacy of the Neurohormonal inhibitors (Captopril 50 mg+prazosin 1 mg only) and direct arteriolar and venular dilators (Intravenous hydralazine 30 mg+oral isosorbide dinitrate 30 mg) used as vasodilator therapy, was undertaken in a randomized, single blind study in 17 Nigerian patients with hypertensive acute left ventricular failure. Both vasodilator regimes separately and significantly reduced the systolic and diastolic blood pressures (P<0.001 ANOVA), heart rate (P<0.001 ANOVA), and the respiratory rate (P<0.05 ANOVA), the double product, but increased the peak expiratory flow rate (P<0.05 ANOVA). However, the neurohormonal antagonists, captopril and prazosin (n=9) caused a statistically significantly greater reduction in heart rate (P<0.05 ANOVA) respiratory rate (P<0.05 ANOVA) and induced a significantly greater increase in the self-paced exercise capacity, 24 h after initiation of treatment, (P<0.02) compared to the hydralazine and isosorbide dinitrate combination (n=8). Five of the nine patients on the neurohormonal antagonist therapy were ambulant at 24 h, compared to none of the eight patients receiving conventional venular and arteriolar dilators hydralazine and isosorbide dinitrate (chi2=5.84 dfi P<0.05). There was a significant inverse correlation between the systolic blood pressure heart rate product, and the distance covered during symptom limited self paced exercise capacity (r=-0.58, P=0.0146 ANOVA). One of eight patients in the hydralazine+isosorbide nitrate combination died, but there was no mortality in the captopril+prazosin group. These findings collectively suggest that captopril+prazosin combination may be a superior vasodilator therapy compared to hydralazine-isosorbide dinitrate, in hypertensive acute pulmonary oedema.

Oral therapy with combined enalapril, prazosin and hydrochlorothiazide in the acute treatment of severe hypertension in Nigerians.

OBJECTIVE: The efficacy, safety, tolerability and speed of onset of the hypotensive action of the combination of oral enalapril (10 mg) prazosin (1 mg) and hydrochlorothiazide (50 mg) has been assessed in 12 Nigerians with severe hypertension (Diastolic BP > or = 115 mmHg). PATIENTS: The ages of the patients ranged from 30-60 years, and the serum creatinine from 52-732 mumol.l-1. The initial blood pressure was 200/130 mmHg. RESULTS: The combination significantly reduced systolic and diastolic blood pressure respectively. The hypotensive action appeared within 0.5 h and led to a fall in BP to 175/120 mmHg, and the peak action occurred at 4 h, when the BP was 138/99 mmHg, and it persisted upto 24 h (160/101 mmHg). Despite the significant fall in blood pressure, no reflex tachycardia was observed. Transient dizziness was seen in 2 patients, but otherwise all claimed improvement in clinical status and a clearer sensorium. CONCLUSION: The combination may be a useful oral treatment for the rapid control of severe hypertension in Blacks.