Daniel Lemogoum

Validity of pulse pressure and augmentation index as surrogate measures of arterial stiffness during beta-adrenergic stimulation.

Objective Increased arterial stiffness is a determinant of cardiovascular mortality. Pulse wave velocity (PWV) is a direct measure of arterial stiffness. Aortic augmentation index (AI) and pulse pressure (PP) are surrogate measures of arterial stiffness. Both PWV, AI and PP increase with cardiovascular risk factors. The aim of this study was to test the validity of AI and PP as surrogate measures of arterial stiffness compared with PWV, during beta-adrenergic stimulation with Isoprenaline (Iso). Design and methods A total of 41 healthy volunteers entered a randomized, double-blind, placebo-controlled, cross-over study. In random order, subjects were given intravenous infusion in equal volume of Iso 8 μg/kg per min (dissolved in glucose 5%) and placebo (glucose 5%). A wash-out period of 25 min was observed between the infusions. Measurements included blood pressure (BP), heart rate (HR), PWV, and AI. PWV were determined using complior (Complior, Artech-Medical, Paris, France). AI and aortic PP were obtained from pulse wave analysis of radial applanation tonometry, using transfer function (SphygmoCor Windows software). Results Baseline AI increased (P < 0.05) with aging, a lower height and a larger diastolic BP (DBP). Iso increased (P < 0.0001) HR, brachial SBP, brachial and aortic PP as compared with placebo. In contrast, Iso decreased (P < 0.05) AI, brachial DBP, peripheral PWV, but not aortic PWV. Decrease of AI induced by Iso was not related to PWV. In stepwise multiple regression changes in HR, brachial SBP and DBP were independent determinants of AI response to Iso (r = 0.78, P < 0.0001). Conclusions Our findings show that AI and PP fail as surrogate measures of arterial stiffness during beta-adrenergic stimulation.

Acute cardiovascular and sympathetic effects of nicotine replacement therapy.

Sympathetic overactivity is implicated in the increased cardiovascular risk of cigarette smokers. Excitatory nicotinic receptors are present on peripheral chemoreceptor cells. Chemoreceptors located in the carotid and aortic bodies increase ventilation (Ve), blood pressure (BP), heart rate (HR), and sympathetic nerve activity to muscle circulation (MSNA) in response to hypoxia. We tested the hypothesis that nicotine replacement therapy (NRT) increases MSNA and chemoreceptor sensitivity to hypoxia. Sixteen young healthy smokers were included in the study (8 women). After a randomized and blinded sublingual administration of a 4-mg tablet of nicotine or placebo, we measured minute Ve, HR, mean BP, and MSNA during normoxia and 5 minutes of isocapnic hypoxia. Maximal voluntary end-expiratory apneas were performed at baseline and at the end of the fifth minute of hypoxia. Nicotine increased HR by 7±3 bpm, mean BP by 5±2 mm Hg, and MSNA by 4±1 bursts/min, whereas subjects breathed room air (all P<0.05). During hypoxia, nicotine also raised HR by 8±2 bpm, mean BP by 2±1 mm Hg, and MSNA by 7±2 bursts/min (all P<0.05). Nicotine increased MSNA during the apneas performed in normoxia and hypoxia (P<0.05). Nicotine also raised the product of systolic BP and HR, a marker of cardiac oxygen consumption, during normoxia, hypoxia, and the apneas (P<0.05). Ve, apnea duration, and O2 saturation during hypoxia and the apneas remained unaffected. In conclusion, sympathoexcitatory effects of NRT are not because of an increased chemoreflex sensitivity to hypoxia. NRT increases myocardial oxygen consumption in periods of reduced oxygen availability.

Ethnic differences in arterial stiffness and wave reflections after cigarette smoking.

Background Smoking increases plasma nicotine. Nicotine releases catecholamines and alters arterial distensibility. The nicotine intake per cigarette is greater and serum cotinine levels, the proximate metabolite of nicotine, are higher in Blacks than in Whites. We tested the hypothesis that cigarette smoking increases the pulse wave velocity (PWV), a marker of arterial stiffness, and the augmentation index (AI), a measure of wave reflection, more in Blacks than in Whites. Methods We matched Black (n = 30) and White (n = 30) smokers for age, gender, body mass index and height. We determined carotid-femoral PWV (PWVCF) and carotid-radial PWV (PWVCR) (Complior), the AI derived from the aortic pressure waveform (applanation tonometry, Sphygmocor), blood pressure, heart rate (HR) and cotinine levels before and after cigarette smoking. We also performed measurements in 16 participants after sham smoking. Results Smoking increased the AI, PWVCF and PWVCR in the whole population (all P < 0.05, n = 60). Increases in the AI and PWV were positively related to serum cotinine levels (all P < 0.05). Smoking increased serum cotinine (P = 0.01) and mean blood pressure (P = 0.03) more, but raised the HR to a lesser extent, in Blacks [+8 ± 4 versus +13 ± 6 beats/min in Whites (mean ± SD), P = 0.01]. Blacks disclosed larger increases in AI adjusted for HR (Blacks, +7.2 ± 8 versus Whites, +4.4 ± 8%; P = 0.03), PWVCF (Blacks, +1.1 ± 0.2 versus Whites, +0.6 ± 0.3 m/s; P < 0.01) and PWVCR (Blacks, +1.4 ± 0.1 versus Whites, +0.7 ± 0.4 m/s; P < 0.01) normalized for the mean blood pressure. No changes were observed with sham smoking. Conclusions Smoking acutely increases the PWV and AI in Blacks more than in Whites. Differences in nicotine metabolism and β-adrenergic sensitivity could explain these findings.

Arterial Stiffness and Wave Reflections in Patients With Sickle Cell Disease

We tested the hypothesis that lower blood pressure and increased vasodilatation reported in sickle cell disease (SCD) patients with hemoglobin SS genotype (SS) are translated by lower arterial stiffness determined by pulse wave velocity (PWV) and wave reflections assessed by augmentation index (AI). We enrolled 20 SS (8 females; 12 male) patients closely matched for age, gender, height, and body mass index to 20 subjects with hemoglobin AA genotype (AA). Carotid–femoral PWV (PWVCF) and carotid–radial PWV (PWVCR) were recorded with the Complior device. Aortic AI was derived from pressure wave analysis (SphygmocoR). PWVCF and PWVCR were lower in SS than in AA (4.5±0.7 m/s versus 6.9±0.9 m/s, P<0.0001 and 6.6±1.2 m/s versus 9.5±1.4 m/s, P<0.0001, respectively). AI was lower in SS than in AA (2±14% versus 11±8%, P=0.02). Multivariate analysis revealed that both PWVCF and PWVCR were negatively associated with hemoglobin SS type and positively related to mean arterial pressure (MAP), whereas AI was positively associated with MAP and total cholesterol (all P<0.0001). Multivariate analysis restricted to SS indicated a positive association between PWVCF and PWVCR with age but a negative association with MAP (R2=0.57 and 0.51, respectively, both P<0.001), whereas MAP and heart rate were independently associated with AI (R2=0.65, P<0.001). This study provides the first evidence that SCD is associated with both lower arterial stiffness and wave reflections. SS patients have a paradoxical negative association between PWV and MAP, suggesting that low MAP does not protect them against arterial stiffness impairment.

Effects of Hunter-Gatherer Subsistence Mode on Arterial Distensibility in Cameroonian Pygmies

We aimed to assess whether arterial distensibility estimated by pulse wave velocity (PWV) and augmentation index (AI) differs between Cameroon traditional pygmies (TPs) on hunter-gather subsistence mode, contemporary pygmies who migrated to semiurban area, and the Bantou farmers (BFs) sharing the same environment. For that purpose, we recorded carotid-femoral PWV (ComplioR) in age and sex carefully matched 20 TPs, 20 contemporary pygmies, and 22 BFs. Aortic AI corrected for heart rate and blood pressures were generated from pressure wave analysis (SphygmoCor). Lipid profile was determined in TP and BF participants. TPs were shorter (P=0.02) with lower body weight (P<0.01) in comparison with contemporary pygmies and BFs. TPs had lower low-density lipoprotein cholesterol but higher high-density lipoprotein cholesterol than BFs (P<0.01). Their PWV (5.81±0.21 m/s) was slower (P=0.006) than that of contemporary pygmies (6.82±0.36 m/s) or BFs (6.93±0.29 m/s); however, after its adjustment for age, mean arterial pressure, and heart rate, the difference was slightly attenuated (P=0.051). PWV adjusted for weight did not differ between groups (P=0.10). In the whole study population but not in TPs taken separately, multivariate regression analysis revealed that PWV was independently associated with mean arterial pressure, age, and TP status (P<0.001), whereas age, mean arterial pressure, and height emerged as independent determinants of aortic AI corrected for heart rate (P<0.001). Aortic AI corrected for heart rate did not differ in the 3 groups. In conclusion, hunter-gather lifestyle is associated with low atherosclerosis risk translated by lower aortic stiffness attributed at least partly to low weight and blunted effects of aging and blood pressures on TP arterial structure and function.

Effect of beta-adrenergic stimulation on pulse wave velocity in black and white subjects.

Background Reduced beta-adrenergic sensitivity has been reported in black subjects. We hypothesized that beta-adrenergic stimulation by isoproterenol would affect pulse wave velocity (PWV), a marker of arterial stiffness, differently in black and white subjects. Methods Healthy normotensive black subjects (n = 21) matched for age, gender, height and body mass index with healthy normotensive white subjects (n = 20), participated in a randomized, double-blind, placebo-controlled cross-over study. The PWV was determined using an automated device at baseline and after 30 min of an equal volume infusion of isoproterenol (8 μg/kg per min) or placebo (dextrose 5%), separated by a washout period of 25 min. Results At baseline, heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) and PWV were comparable in black and in white subjects. Placebo had no significant effect on haemodynamic variables. Isoproterenol increased HR, SBP and pulse pressure and decreased DBP with a comparable magnitude in both groups. Compared with placebo, isoproterenol decreased carotid-femoral PWV in white (from 5.9 ± 1.2 to 5.7 ± 1.1 m/s, means ± SD, P = 0.05), but not in black subjects (from 6.2 ± 1.3 to 6.6 ± 1.7 m/s, P = 0.1). The difference in response between black and white subjects was significant (P = 0.04). Isoproterenol decreased carotid-radial PWV only significantly in white subjects. Conclusion These results are compatible with the hypothesis of an altered beta-adrenergic sensitivity, which is expressed by a blunted effect of isoproterenol on arterial stiffness in black subjects.

Increased burden and severity of metabolic syndrome and arterial stiffness in treatment-naïve HIV+ patients from Cameroon.

Background Human immunodeficiency virus (HIV) and its therapy are associated with increased aortic stiffness and metabolic syndrome (MetS) phenotype in Caucasian patients. We hypothesized that, independently of antiretroviral therapy, HIV infection in native black African patients is associated with increased burden of cardiometabolic risk factors that may accelerate arterial structural damage and translate into increased aortic stiffness. Patients and methods Ninety-six apparently healthy Cameroonian subjects (controls) were compared to 108 untreated Cameroonian HIV+ patients (HIV-UT) of similar age. In each participant, pulse wave velocity (Complior), aortic augmentation index (SphygmoCor), brachial blood pressure (Omron 705 IT), fasting plasma glucose (FPG), and lipids were recorded, as well as the prevalence and severity of MetS, based on the American Heart Association/National Heart, Lung, and Blood Institute score ≥3/5. Results Prevalence of impaired fasting glucose (FPG 100–125 mg · dL−1) and of diabetes (FPG > 125 mg · dL−1) was higher in HIV-UT than in controls (47% versus 27%, and 26% versus 1%, respectively; both P < 0.01). Fasting triglycerides and the atherogenic dyslipidemia ratio were significantly higher in HIV-UT than in controls. Hypertension prevalence was high and comparable in both groups (41% versus 44%, respectively; not significant). HIV-UT patients exhibited a twice-higher prevalence of MetS than controls (47% versus 21%; P = 0.02). Age- and sex-adjusted pulse wave velocity was higher in HIV-UT than in controls (7.5 ± 2.2 m/s versus 6.9 ± 1.7 m/s, respectively; P = 0.02), whereas aortic augmentation index was significantly lower (6% ± 4% versus 8% ± 7%, respectively; P = 0.01). Conclusion Similar to Caucasian populations, native Cameroonian HIV-UT patients showed a higher prevalence of MetS and its phenotype, associated with increased aortic stiffness, an early marker of atherosclerosis.

[Hypertension in the adult Congolese population of Southern Kivu: Results of the Vitaraa Study].

OBJECTIVE To assess the prevalence of cardiovascular risk factors in adult urban and rural Congolese subjects. METHODS We obtained anthropometric data and information on life habits and medical history in 699 people ≥ 20 years, 444 in an urban, 255 in a rural setting. We determined the body mass index and recorded two blood pressure measurements that were averaged for analysis. Hypertension was BP ≥ 140/90mmHg, awareness and/or use of antihypertensive treatment. Diabetes mellitus was self-reported diagnosis or a casual glycemia ≥ 200mg/dL. We assessed the probability of hypertension in stepwise multiple logistic analysis, and awareness, and control of hypertension. RESULTS We found higher (P<0.001) prevalence in the urban than the rural subjects for hypertension (41.4% vs 38.1%), diabetes (4.9% vs 3.2%), overweight/obesity (37.6% vs 16.5%), abdominal obesity (30.9% vs 12.9%), use of alcohol (45% vs 17.6%) and smoking (11.6% vs 1.2%). Hypertension was associated (P<0.05) to aging in 51.3%, overweight/obesity in 54.5%, diabetes in 69%, abdominal obesity in 63.8%, low physical activity in 42.4%, to stress in urban environment in 43.2% and professional position (executives: 53.2%, workers: 38.6%). Of these hypertensive subjects, 57.5% were unaware, 30.5% were treated, with control achieved in only 13.6% (17.4% women vs 6.9% men; P<0.01). In the logistic model, the probability of hypertension increased with age (OR for age>55 years: 2.35; P<0.001), overweight/obesity (2.22; P<0.001) and diabetes mellitus (2.67; P<0.05). CONCLUSIONS Our results indicate a heavy burden of uncontrolled risk factors in the Congolese population the potential complications of which run at a high mortality rate. They highlight the need for reasonable prevention measures at the population level.

Rationale and design of the Newer Versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial

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.

Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients

BackgroundThe 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.MethodsPatients 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.ResultsAt 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/m2), 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.ConclusionsNOAAH (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.