The effects of enalapril-digoxin-diuretic combination therapy on nutritional and anthropometric indices in chronic congestive heart failure: preliminary findings in cardiac cachexia.

BACKGROUND: Body wasting is a clinical feature of a variety of chronic illnesses including congestive heart failure. The wasting associated with chronic congestive heart failure (cardiac cachexia) has recently been shown to portend a worse prognosis, and it is an independent predictor of mortality. The mechanisms underlying cardiac cachexia are multi-factorial, including metabolic, nutritional, neuroendocrine and immunological aberrations. There is, however, no direct evidence that current medical treatment reverses cachexia in chronic heart failure. METHODS: The effect of enalapril, digoxin and frusemide combination on clinical, biochemical and anthropometric indices were determined in eight cachectic Nigerians with chronic congestive heart failure [body mass index (BMI) 20.80+/-2.7 kg/m(2), left ventricular ejection fraction 29+/-4% and LV mass index 161+37 g/m(2)] at baseline, and again after 3 and 6 months of therapy. Ten age- and sex-matched healthy volunteers whose anthropometric data were concurrently measured served as controls. RESULTS: The anthropometric and clinical measurements were significantly (P<0.001) reduced in heart failure compared to the healthy controls. Congestive hepatomegaly significantly regressed from 161+/-20 mm to 123+/-13 mm after 6 months therapy (P<0.001 ANOVA). There was a significant increase in the sum of four skin fold thickness from 27.6+/-3.3 mm to 30.1+/-3.9 mm at 6 months (P<0.001 ANOVA) 95% confidence intervals for the difference being 1.42 to 3.4 mm. There was a significant increase in the mid-upper arm circumference (P<0.001 ANOVA) with a 95% confidence interval of 0.87-2.1 cm, and a similar trend for increased mid-thigh circumference (95% confidence limits 0.93-5.30 cm) was apparent. Plasma albumin and sodium increased significantly (P<0.05) from 30.1+/-3.8 g/l and 136+/-5.9 mmol/l to 32.9+/-2.5 g/l and 139+/-3.9 mmol/l, respectively. There was a positive and significant correlation between the treatment induced increases in plasma albumin and the increase in mid-upper arm circumference (y=0.25x+0.8, r=0.76, P=0.03 ANOVA) but not with the change in skin fold thickness. CONCLUSION: The preliminary results demonstrate increased subcutaneous fat (increased skin fold thickness), greater muscle bulk (increased mid-upper arm and thigh circumferences) together with a significant elevation in plasma albumin and the hematocrit, which reflect the anabolic state in patients treated with ACE inhibitor-digoxin-diuretic with congestive heart failure.

Shifting trends in the pharmacologic treatment of hypertension in a Nigerian tertiary hospital: a real-world evaluation of the efficacy, safety, rationality and pharmaco-economics of old and newer antihypertensive drugs.

The current prescription patterns for essential hypertension and the efficacy, safety, tolerability and cost-effectiveness of the newer antihypertensive drugs were evaluated in Nigerian patients. The findings were compared with that of a previous study conducted in the same tertiary hospital 10 years earlier. A cross-sectional evaluation of blood pressure (BP) control in a hypertension clinic was undertaken among 150 Nigerian patients aged 61 +/- 12 years (55% females), with a duration of treatment on a particular drug class or combination of 9 +/- 3 months. The initial blood pressure was 176 +/- 20/108 +/- 11 mmHg and 22% of the patient had concurrent diabetes mellitus. Thiazide diuretics (D) alone or in combination remained the most commonly prescribed drugs in 56% of all patients. There were significant increases in the prescriptions of calcium channel blockers (CCBs) (51%), P < 0.0001, and ACE-inhibitors (ACEIs) (24%), P < 0.0001, but a slight reduction in the use of methyldopa, and fixed drug combinations (P < 0.01) compared to the previous study. The fall in systolic blood pressure on D (r = 0.65, P < 0.001) or CCB (r = 0.48, P < 0.02) was significantly correlated with the initial systolic blood pressure, but not age. More patients achieved normotension BP < 140/90 mmHg on CCB monotherapy (71%), than D monotherapy (56%). Combination therapy with ACEIs + D or methyldopa+thiazides normalized BP in 63 and 68%, respectively. Pulse pressure, a surrogate marker for cardiovascular complications and mortality in essential hypertension, was significantly reduced (P < 0.01) equally by all treatments, with 95% confidence intervals ranging from -28 to -1 mmHg. However, hypertensive-diabetic (HT-DM) patients (n = 33) exhibited no significant change in pulse pressure in response to treatment. Adverse drug reactions that occurred in 11% were impotence or postural dizziness with D, headache and pitting oedema with CCB, and dry cough with ACEI. Pharmaco-economic comparison of the drug classes revealed that for every US dollar (dollar) spent per month, the percentage of treated patients attaining normotension was 18.6 for D, 4.73 for CCB, 3.5 for ACEI + D and 13.6 for methyldopa + thiazides. A combination of ACEI + CCB or D was the preferred treatment for hypertensive-diabetic Nigerians, but only 24% attained a BP < 130/85 mmHg. These results demonstrate a shift in trend to a more rational and efficacious treatment of hypertension over a 10 year period. This may be associated, at least in part, with the intensive and continuous education of the prescribers in rational drug use and the introduction of a hospital formulary. Methyldopa is still a highly efficacious and cost-effective drug in this population. Black HT-DM Africans still constitute a subgroup who not only require more and costlier antihypertensive drugs, but whose BP control is suboptimal, and exhibit a poor therapeutic response to other risk factors (pulse pressure) that constitute a continuing risk for cardiovascular mortality.

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.

Chronotropic dose response of atropine in Nigerians with congestive heart failure: assessment of ethnic variation and reversibility of parasympathetic dysfunction.

Both ethnicity and disease states may influence cardiac parasympathetic tone. We evaluated the cardiac vagal activity in 9 Nigerians aged 57(11) with congestive heart failure, and 9 age- and sex-matched healthy controls aged 51(11) years, using a cumulative low dose atropine response curve. All subjects demonstrated bradycardia at low doses (100 microg-400 microg) and tachycardia at higher doses (600 microg-1,000 microg). However, both the bradycardic and the tachycardic responses were attenuated in heart failure patients compared to controls: bradycardia -1.1(1.5) beats/min in heart failure patients vs -7.1(2.2) beats/min in controls (P<.01) and tachycardia +4(1.5) beats/min in heart failure patients vs +14.3(3) beats/min in healthy controls (P<.01). EC50 values for brachycardia and tachycardia calculated from the dose response curves were significantly higher in healthy controls compared to heart failure patients, for bradycardia 69(39) microg versus 11(1.6) microg (P<.01) and tachycardia 682(61) microg vs 254(84) microg (P<.01). Treatment of heart failure for 4 weeks with furosemide, digoxin and angiotensin converting enzyme inhibitor (enalapril) caused a significant increase in the magnitude of both the bradycardic responses from -1.1(1.5) beats/min to -4.4(0.9) beats/min after treatment, and tachycardic responses from +4(1.5) beats/min to +10.(2.3) beats/min 4 weeks after treatment (P<.05). After 4 weeks of treatment, EC50 was also increased significantly toward normal values. For tachycardia, the values were 254(88) microg before treatment vs 529(78) microg after treatment (P<.05); and for bradycardia, the values were 2.5(1.6) microg before treatment vs 30(13) microg after treatment (P<.05). These findings demonstrate the early bradycardic effect of atropine in Black Africans (both healthy controls and heart failure patients), contradicting earlier reports of its absence in the negroid race. This confirms the reduction in cardiac parasympathetic responsiveness (both maximal heart rate change and EC50) in hypertensive heart failure using a pharmacological assay. It demonstrates the augmentation and amelioration of cardiac vagal tone with enalapril-dixogin-diuretic therapy in non-ischemic heart failure, and the sequential utility of the low dose atropine-chronotropic response in assessing cardiac parasympathetic activity.

A three year clinical review of the impact of angiotensin converting enzyme inhibitors on the intra hospital mortality of congestive heart failure in Nigerians.

Angiotensin converting enzymes inhibitors are now regarded as the cornerstone of congestive heart failure therapy owing to established reduction in mortality and the symptomatic amelioration following their use. Although the response to converting enzyme inhibitor therapy may be influenced by race, we have reported a trend to reduce intra hospital mortality, the correction of hyponatremia and shortened hospitalization in Nigerians treated with converting enzyme inhibitors. We have now conducted an extended retrospective study, to evaluate the trends in the use of enalapril or captopril and its impact on prognosis in Nigerian patients with heart failure alone, admitted between January 1992 to December 1994. The proportion of heart failure treated with (captopril or enalapril) increased from 37pc in 1992, to 50pc in 1993, to 65pc in 1994. The demographic variables and cause of heart disease were similar in patients treated with converting enzyme inhibitors (n = 55) and those treated conventionally (n = 36). The cumulative mortality among converting enzyme inhibitors treated patients, was (8/55, 14pc) compared to patients not treated (17/36, 48pc) x2 = 12.4; p < 0.0001. There was no sex predilection in mortality (M = 25pc, F = 28pc, mean 27pc). However, initial serum Na+,125mmol was significantly (x2 = 11.1; p < 0.001) more common in the dead patients, 25pc compared to the survivors discharged home 7.5pc. The median hospital stay was 17 days in captopril treated survivors (range two to 44 days) and 19 days (range four to 67 days) in conventionally treated patients. Thus converting enzyme inhibitor therapy may reduce intra hospital mortality in Black Africans hospitalized for congestive heart failure and shorten hospital stay, despite the epidemiologically low plasma renin in Blacks. Hyponatremia may be a poor prognostic index in heart failure in our patients, and its reversal by converting enzyme inhibitors may reflect neurohormonal inhibitor. Earlier and more wide spread use of angiotensin converting enzyme inhibitors in Nigerian and Black Africans with chronic heart failure is now clearly indicated.

Angiotensin converting enzyme inhibitor induced cough in Nigerians.

A persistent dry cough is the commonest class of adverse reaction to Angiotensin converting enzyme inhibitors (ACE-I). This ACE-I induced cough appears to exhibit interracial differences being commoner in Chinese subjects as compared to Caucasians. We conducted a cross sectional study of one hundred (100) patients (63 males and 37 females) on ACE-I to determine the prevalence of ACE-induced cough in Nigerians, a Negroid population. Twenty seven patients (27%) had ACE-induced cough and four (4%) had withdrawal of ACE-I therapy on account of cough. The prevalence of ACE-I induced cough was significantly higher amongst females (43%) as compared to males (17%) p < 0.01. The biological basis for the apparent racial and gender differences in ACE-I induced cough requires further study.

Cardiac autonomic function in Blacks with congestive heart failure: vagomimetic action, alteration in sympathovagal balance, and the effect of ACE inhibition on central and peripheral vagal tone.

Cardiac autonomic dysfunction is common in heart disease with or without congestive heart failure, and can cause sudden cardiac death. However, cardiac autonomic abnormalities in non-ischemic (hypertensive) heart failure, which is prevalent in Black Africans is poorly documented. We conducted a cross-sectional study of 32 patients with congestive heart failure, mostly secondary to hypertension (aged 52 +/- 15 years, with ejection fraction of 0.38 +/- 11) and 30 age- and sex-matched healthy volunteers (aged 51 +/- 11 years, 14 males/16 females). Cardiac autonomic function was assessed by the Valsalva's maneuver, respiratory sinus arrhythmia (for cardiac vagal tone) and the pressor and chronotropic changes following forearm isometric handgrip exercise and the assumption of upright posture (tests of sympathetic function). The exercise tolerance of the cardiac patients was assessed by the distance covered during 6 min of walking. The Valsalva ratio was significantly lower in chronic heart failure, 1.10 +/- 0.08 compared to the healthy controls 1.47 +/- 0.20 (p<0.001). Specifically, the phase IV bradycardia in heart failure, was significantly attenuated to 650 +/- 121 msec compared to the value of 935 +/- 101 msec in healthy controls (p<0.001). The phase 11 Valsalva tachycardia did not differ between the patients and controls. The respiratory sinus arrhythmia was also significantly reduced in chronic heart failure (p<0.05) compared to controls. Treatment of the heart failure patients with enalapril-digoxin and diuretics by 4 weeks, resulted in a reversal of the autonomic abnormalities. The phase IV bradycardia increased significantly to 798 +/- 164 msec (p<0.01) and the Valsalva ratio to 1.35 +/- 0.25 (p<0.01) and the respiratory sinus arrhythmia increased toward normal. There was close positive correlation between the Valsalva's ratio and the 6 min self paced distance covered (r = 0.44, p = 0.03 ANOVA), and a weak inverse correlation to cardiac size and cardiothoracic ratio (r = -0.31, p = 0.09). This study demonstrates cardiac autonomic dysfunction (especially reduced vagal tone) in Black Nigerians with mainly non-ischemic congestive heart failure. The parasympathetic dysfunction significantly correlates with severity of heart failure. Current treatment reverses autonomic dysfunction to values seen in healthy age matched controls, mainly through augmentation of cardiac parasympathetic activity.

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.