The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer ...versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic.
Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure <140/<90 mmHg during six months, the doses of bisoprolol and amlodipine should be increased to 10 mg/day with the possible addition of up to 2 g/day α-methyldopa.
At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass index (28.2 kg/m(2)), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study.
NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible.
Chronic kidney disease (CKD) is a major cause of cardiovascular morbidity and mortality all over the world. The combined effect of volume and pressure overload seen in patients with CKD is the ...primary cause of left ventricular hypertrophy (LVH). Though it accounts for a significant proportion of patients dying in hospitals in Nigeria, information on CKD in African Blacks is lacking. This study evaluates the prevalence of LVH and factors affecting it in pre-dialysis patients by using echocardiography.
One hundred consecutive patients with CKD who were attending the medical outpatient and renal clinics of University of Nigeria Teaching Hospital, Enugu, who satisfied the inclusion criteria were screened for the study. Eighty-eight patients completed the study. Forty-five age- and sex-matched subjects were selected as controls. Clinical and laboratory parameters and echocardiographic indices were measured.
Left ventricular hypertrophy (LVH), defined in absolute terms as left ventricular mass index >134 g/m2 in men and >110 g/m2 in women was present in 95.5% of patients and 6.7% of controls. The most prevalent type of LVH was eccentric hypertrophy, which was found in 54.6%, while concentric was seen in 40.9%. Hypertension was present in 85.2% of the patients. The predominant causes of CKD were chronic glomerulonephritis (43.2%), hypertension (25%), and diabetes mellitus (14.8%). All the patients studied had advanced CKD, either stage 4 or 5 of the Kidney Disease Outcome Quality Initiative classification of CKD. Stepwise method of multiple linear regressions identified mean arterial pressure (32%), hemoglobin concentration (22%), male sex (17%), and creatinine clearance (24%) as predictors of LVH in CKD.
This study showed a strong association between CKD and LVH in patients in developing countries at the time of first evaluation by a nephrologist. It demonstrated a high prevalence of LVH in patients at first evaluation. The patients were often anemic and had severe hypertension even at first presentation. Early detection and treatment of causes of CKD should be pursued aggressively at the primary prevention level, as has been advocated by the International Society of Nephrology to reduce the effects of CKD and its attendant complications in the society.
Abstract
Background. Compared with Caucasians, African Americans have lower heart rate variability (HRV) in the high-frequency domain, but there are no studies in blacks born and living in Africa. ...Methods. In the Newer versus Older Antihypertensive agents in African Hypertensive patients trial (NCT01030458), patients (30-69 years) with uncomplicated hypertension (140-179/90-109 mmHg) were randomized to single-pill combinations of bisoprolol/hydrochlorothiazide (R) or amlodipine/valsartan (E). 72 R and 84 E patients underwent 5-min ECG recordings at randomization and 8, 16 and 24 weeks. HRV was determined by fast Fourier transform and autoregressive modelling. Results. Heart rate decreased by 9.5 beats/min in R patients with no change in E patients (− 2.2 beats/min). R patients had reduced total (− 0.13 ms²; p = 0.0038) and low-frequency power (− 3.6 nu; p = 0.057), higher high-frequency (+ 3.3 nu; p = 0.050) and a reduced low- to high-frequency ratio (− 0.08; p = 0.040). With adjustment for heart rate, these differences disappeared, except for the reduced low-frequency power in the R group (− 4.67 nu; p = 0.02). Analyses confined to 39 R and 47 E patients with HRV measurements at all visits or based on autoregressive modelling were confirmatory. Conclusion. In native black African patients, antihypertensive drugs modulate HRV, an index of autonomous nervous tone. However, these effects were mediated by changes in heart rate except for low-frequency variability, which was reduced on beta blockade independent of heart rate.
Use of race adjustment in estimating glomerular filtration rate (eGFR) has been challenged given concerns that it may negatively impact the clinical care of Black patients, as it results in Black ...patients being systematically assigned higher eGFR values than non-Black patients. We conducted a systematic review to assess how well eGFR, with and without race adjustment, estimates measured GFR (mGFR) in Black adults globally. A search across multiple databases for articles published from 1999 to May 2021 that compared eGFR to mGFR and reported outcomes by Black race was performed. We included studies that assessed eGFR using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI.sub.Cr) creatinine equations. Risk of study bias and applicability were assessed with the QUality Assessment of Diagnostic Accuracy Studies-2. Of 13,167 citations identified, 12 met the data synthesis criteria (unique patient cohorts in which eGFR was compared to mGFR with and without race adjustment). The studies included patients with and without kidney disease from Africa (n = 6), the United States (n = 3), Europe (n = 2), and Brazil (n = 1). Of 11 CKD-EPI equation studies, all assessed bias, 8 assessed accuracy, 6 assessed precision, and 5 assessed correlation/concordance. Of 7 MDRD equation studies, all assessed bias, 6 assessed accuracy, 5 assessed precision, and 3 assessed correlation/concordance. The majority of studies found that removal of race adjustment improved bias, accuracy, and precision of eGFR equations for Black adults. Risk of study bias was often unclear, but applicability concerns were low. Our systematic review supports the need for future studies to be conducted in diverse populations to assess the possibility of alternative approaches for estimating GFR. This study additionally provides systematic-level evidence for the American Society of Nephrology-National Kidney Foundation Task Force efforts to pursue other options for GFR estimation.
Abstract
Background. Sub-Saharan Africa experiences an epidemic surge in hypertension. Studies in African Americans led to the recommendation to initiate antihypertensive treatment in Blacks with a ...diuretic or a low-dose fixed combination including a diuretic. We mounted the Newer versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial to compare in native African patients a fixed combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic. Methods. Patients aged 30-69 years with uncomplicated hypertension (140-179/90-109 mmHg) and two or fewer associated risk factors are eligible. After a 4-week run-in period off treatment, 180 patients will be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg or amlodipine/valsartan 5/160 mg. To attain and maintain blood pressure below 140/90 mmHg during 6 months of follow-up, the doses of bisoprolol and amlodipine in the combination tablets will be increased to 10 mg/day with the possible addition of α-methyldopa or hydralazine. NOAAH is powered to demonstrate a 5-mmHg between-group difference in sitting systolic pressure with a two-sided p-value of 0.01 and 90% power. NOAAH is investigator-led and complies with the Helsinki declaration. Results. Six centers in four sub-Saharan countries started patient recruitment on September 1, 2010. On December 1, 195 patients were screened, 171 were enrolled, and 51 were randomized and followed up. The trial will be completed in the third quarter of 2011. Conclusions. NOAAH (NCT01030458) is the first randomized multicenter trial of antihypertensive medications in hypertensive patients born and living in sub-Saharan Africa.
Background
Few studies assessed arterial stiffness in Black hypertensive patients born and living in sub-Saharan Africa, where cardiovascular disease reaches epidemic proportions.
Methods
The Newer ...versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial is currently recruiting native African patients to compare the efficacy of various antihypertensive drugs given once daily as single-pill combinations. Two centres engaged in pulse wave analysis and measured carotid–femoral pulse wave velocity (PWV). Statistical methods included single and multiple linear regressions.
Results
Of 172 patients screened, 116 entered the ancillary study on central haemodynamics (51.3% women; mean age 52.7 years; untreated blood pressure 147.6/87.1 mm Hg). The augmentation indexes were higher (
p
< 0.0001) in women than men, both peripherally (pAI, 11.1 vs. −10.6%) and centrally (cAI, 39.0 vs. 28.0%). PWV (8.91 m/s) and central pulse pressure (cPP, 48.7 mm Hg) were similar (
p
> 0.844) in both sexes. pAI and cAI increased with female sex and mean arterial pressure, but decreased with heart rate and body mass index. cPP increased with age and mean arterial pressure. PWV increased with age and mean arterial pressure. Patients with measurements above the age-specific thresholds determined in healthy Black South Africans amounted to 0 for cAI, 1 (1.2%) for cPP, and 11 (18.3%) for PWV.
Conclusion
NOAAH patients have measures of arterial stiffness similar to those of a healthy Black reference population with determinants as reported in the literature. Our observations highlight the potential for the prevention of irreversible arterial damage by timely treating sub-Saharan hypertensive patients to target blood pressure levels.
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