Catharina M. C. Mels

Are behavioural risk factors to be blamed for the conversion from optimal blood pressure to hypertensive status in Black South Africans? A 5-year prospective study

BACKGROUND Longitudinal cohort studies in sub-Saharan Africa are urgently needed to understand cardiovascular disease development. We, therefore, explored health behaviours and conventional risk factors of African individuals with optimal blood pressure (BP) (≤ 120/80 mm Hg), and their 5-year prediction for the development of hypertension. METHODS The Prospective Urban Rural Epidemiology study in the North West Province, South Africa, started in 2005 and included African volunteers (n = 1994; aged > 30 years) from a sample of 6000 randomly selected households in rural and urban areas. RESULTS At baseline, 48% of the participants were hypertensive (≥ 140/90 mmHg). Those with optimal BP (n = 478) were followed at a success rate of 70% for 5 years (213 normotensive, 68 hypertensive, 57 deceased). Africans that became hypertensive smoked more than the normotensive individuals (68.2% vs 49.8%), and they also had a greater waist circumference [ratio of geometric means of 0.94 cm (95% CI: 0.86-0.99)] and greater amount of γ-glutamyltransferase [0.74 U/l (95% CI: 0.62-0.88)] at baseline. The 5-year change in BP was independently explained by baseline γ-glutamyltransferase [R(2) = 0.23, β = 0.13 U/l (95% CI: 0.01-0.19)]. Alcohol intake also predicted central systolic BP and carotid cross-sectional wall area (CSWA) at follow-up. Waist circumference was another predictor of BP changes [β = 0.18 cm (95% CI: 0.05-0.24)] and CSWA. HIV infection was inversely associated with increased BP. CONCLUSIONS During the 5 years, 24% of Africans with optimal BP developed hypertension. The surge in hypertension in Africa is largely explained by modifiable risk factors. Public health strategies should focus aggressively on lifestyle to prevent a catastrophic burden on the national health system.

Defensive coping facilitates higher blood pressure and early sub–clinical structural vascular disease via alterations in heart rate variability: The SABPA study

OBJECTIVES Defensive coping (AC) responses in urban African males have been associated with vascular responsiveness, partly explaining autonomic nervous system dysfunction. We therefore aimed to assess whether AC responses facilitate higher blood pressure and early sub-clinical structural vascular disease via alterations in frequency- and time-domain heart rate variability (HRV) responses. METHODS We included 355 African and Caucasian men and women without pre-existing atrial fibrillation, aged 45 ± 9 years. Significant interaction on main effects (coping × ethnicity × gender) for left carotid intima media thickness far wall (L-CIMTf) and cross sectional wall area values necessitated selection of AC responders above mean via the Coping Strategy Indicator. We collected B-mode ultrasound L-CIMTf, ambulatory BP and-HRV data. Overnight fasting blood was obtained. RESULTS Overall, Africans and AC Africans, mostly men, revealed a poorer lifestyle profile, higher prevalence of hypertensive status, disturbed sympathovagal balance and depressed HRV temporal and geometric patterns compared to the Caucasians (P ≤ 0.05). Moderately depressed non-linear and time-domain HRV (SDNN <100 ms) was prevalent in 28% of Africans compared to 11% of Caucasians. A similar trend was shown for the AC African participants (32%) compared to Caucasians (16%). Only depressed HRV time-domain (SDNN: adj. R(2) = 0.34; β = -0.24; p = 0.08) and vagal-impaired heart rate responses (RMSSD: adj. R(2) = 0.28; β = -0.28; p < 0.05) were associated with higher blood pressure and early structural vascular changes in AC African men. CONCLUSION Defensive coping facilitated autonomic nervous system dysfunction, which was associated with higher blood pressure and sub-clinical structural vascular disease in an African male cohort.

Masked hypertension and its associated cardiovascular risk in young individuals: the African-PREDICT study.

Hypertension prevalence is increasing globally, yet little is known about the occurrence of masked hypertension (MHT) in young, sub-Saharan African adults, and how it relates to elevated cardiovascular risk. The African-PREDICT study (recruitment based on normotensive clinic blood pressure (BP)) determined the frequency of MHT and its relationship with arterial stiffness and biochemical markers of inflammation and endothelial activation. We included men and women (n=352), 20–30 years, screened for normotensive clinic BP (54% white, 40% men). Clinic BP, ambulatory blood pressure monitoring (ABPM), central systolic pressure, aortic pulse wave velocity (aPWV), augmentation index, anthropometry, physical activity and biochemical markers of cardiovascular risk were assessed (lipids, glucose, insulin, markers of endothelial activation and inflammation). Eighteen percent of the study population had MHT (60% white, 68% men). Those with MHT had increased adiposity, clinic-, ABPM- (24-h, day and night) and central-BP (within normal ranges), heart rate, aPWV and biochemical markers of cardiovascular risk, compared with normotensives (all P<0.05). Using multivariable adjusted odds ratios, we found that MHT was associated with increased likelihood for higher aPWV (odds ratio (OR)=1.567, P=0.010), insulin (OR=1.499, P=0.049), monocyte chemoattractant protein-1 (OR=1.499, P=0.026), vascular cellular adhesion molecule (OR=1.409, P=0.042) and C-reactive protein (OR=1.440, P=0.044). In a young adult (supposedly healthy) cohort, the occurrence of MHT is alarming, especially since MHT further demonstrated elevated cardiovascular risk via increased adiposity, arterial stiffness, endothelial activation and inflammation. Detection of MHT is crucial to increase awareness of elevated cardiovascular risk, and to ensure the required lifestyle and/or pharmaceutical interventions.

Exploring the link between cardiovascular reactivity and end-organ damage in African and Caucasian men: the SABPA study.

BACKGROUND Heart failure in the African population is reaching alarming levels. Increased afterload as a result of increased vasoconstriction during stress may lead to impaired ventricular function and stroke volume (SV) as well as vascular hypertrophy. In this study, we challenged the cardiovascular system in order to evaluate the possible contribution of indicators of α-adrenergic vasoconstriction (i.e., vascular resistance and SV reactivity) on left ventricular mass and carotid intima-media thickness (CIMT) in African and Caucasian men. METHODS We evaluated 101 African and 101 Caucasian male schoolteachers. Ambulatory blood pressure measurements were taken. Total peripheral resistance, Windkessel compliance and SV, and resting and reactivity values were obtained using a Finometer device while the Stroop color word conflict test was being applied. The electrocardiogram was recorded to obtain the Cornell product as indication of left ventricular mass. The CIMT was measured and the cross-sectional wall area (CSWA) calculated. RESULTS African men showed higher total vascular resistance resting values as well as higher positive reactivity values compared with Caucasian men. The SV decreased significantly during stress in African men while resting blood pressure and the Cornell product value increased. SV showed a consistent association with left ventricular mass (β = -0.21; P = 0.04) and CSWA (β = -0.24; P = 0.01) in single and multiple regression analyses. No such associations were evident in the Caucasian men. CONCLUSIONS African men showed a suppressed SV, possibly as a result of an increased ventricular afterload leading to end-organ damage.

Compromised bioavailable IGF-1 of black men relates favourably to ambulatory blood pressure: The SABPA study.

OBJECTIVES Insulin-like growth factor-1 (IGF-1) has potent endothelial-protective, anti-platelet and anti-thrombotic activities, and also exerts mitogenic and proliferatory actions on vascular smooth muscle cells. Conflicting reports exist regarding the role of IGF-1 in vascular protection and atherogenesis. We therefore investigated the relationships of ambulatory blood pressure (BP) and carotid intima-media thickness (cIMT) with a range of components of the IGF-1 axis in a bi-ethnic population. METHODS We included black (N = 86) and white (N = 101) men and measured growth hormone, total IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), and pregnancy-associated plasma protein-A (PAPP-A) levels. RESULTS Ambulatory BP was almost 10 mmHg higher in black men (137/88 mmHg versus 128/80 mmHg; both p < 0.001), accompanied by an adverse profile of the IGF-axis for all measured components (all p < 0.01), including reduced bioavailable IGF-1 (IGF-1/IGFBP-3; p = 0.006) and tissue IGF-1 accessibility index as represented by IGF-1.PAPP-A/IGFBP-3 (p < 0.001). Single, partial and multiple regression analyses confirmed an independent inverse association between ambulatory systolic BP and bioavailable IGF-1 in black men (R(2) = 0.24; β = -0.22; p = 0.035). cIMT was similar in the ethnic groups (p = 0.34), and was negatively associated with bioavailable IGF-1 in white men (R(2) = 0.42; β = -0.17; p = 0.039) prior to adjustment for γ-glutamyl transferase (R(2) = 0.45; β = -0.10; p = 0.25). CONCLUSION Ambulatory systolic BP is inversely related to bioavailable IGF-1 in black men who displayed low IGF-1 concentrations. An inverse relation was found between cIMT and IGF-1 in white men, which disappeared after correction for γ-glutamyl transferase - opposing reports of a detrimental role of IGF-1 in the early stages of atherogenesis.

Increased Excretion of C4-Carnitine Species after a Therapeutic Acetylsalicylic Acid Dose: Evidence for an Inhibitory Effect on Short-Chain Fatty Acid Metabolism

Acetylsalicylic acid and/or its metabolites are implicated to have various effects on metabolism and, especially, on mitochondrial function. These effects include both inhibitory and stimulatory effects. We investigated the effect of both combined and separate oral acetylsalicylic acid and acetaminophen administration at therapeutic doses on the urinary metabolite profile of human subjects. In this paper, we provided in vivo evidence, in human subjects, of a statistically significant increase in isobutyrylcarnitine after the administration of a therapeutic dose of acetylsalicylic acid. We, therefore, propose an inhibitory effect of acetylsalicylic acid on the short-chain fatty acid metabolism, possibly at the level of isobutyryl-CoA dehydrogenase.

Cardiometabolic markers to identify cardiovascular disease risk in HIV-infected black South Africans

BACKGROUND The prevalence of HIV is the highest in sub-Saharan Africa; South Africa (SA) is one of the most affected countries with the highest number of adults living with HIV infection in the world. Besides the traditional risk factors for cardiovascular disease (CVD) in the general population, in people living with HIV there are specific factors - chronic inflammation, metabolic changes associated with the infection, therapy, and lipodystrophy - that potentially increase the risk for developing CVD. OBJECTIVE This study proposes a screening discriminant model to identify the most important risk factors for the development of CVD in a cohort of 140 HIV-infected black Africans from the North West Province, SA. METHODS Anthropometric measures, systolic blood pressure, diastolic blood pressure and the carotid-dorsalis pedis pulse wave velocity were determined. Blood was analysed to determine the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, triglycerides (TGs) and glucose. Partial least squares discriminant analysis was performed as a supervised pattern recognition method. Independent Students t-tests were further employed to compare the means of risk factors on interval scales; for comparison of categorical risk factors between groups, chi2 tests were used. RESULTS A TG:HDL-C ratio > or = 1.49, TC:HDL-C ratio > or = 5.4 and an HDL-C level < or = 0.76 mmol/l indicated CVD risk in this cohort of patients living with HIV. CONCLUSION The results have important health implications for black Africans living with HIV as these lipid levels may be a useful indicator of the risk for CVD.

Urinary albumin excretion from spot urine samples predict all-cause and stroke mortality in Africans.

BACKGROUND Increased urinary albumin excretion reflects general vascular damage and predicts adverse cardiovascular and renal outcomes. Albuminuria can be determined from easily collected spot urine samples, especially in low-resource settings. However, no prognostic evidence exists for Africans. METHODS We followed clinical outcomes in 1,061 randomly selected non diabetic, human immunodeficiency virus (HIV)-negative Africans (mean age: 51.5 years; 62.0% women). Baseline urinary albumin-to-creatinine ratio was assessed from spot urine samples. RESULTS Over a median follow-up of 4.52 years, 132 deaths occurred, of which 47 were cardiovascular related. The urinary albumin-to-creatinine ratio averaged 6.1 μg/mg (5th to 95th percentile interval; 1.2-70.0). In multivariable-adjusted analyses, urinary albumin excretion predicted all-cause mortality (hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.07-1.48; P = 0.006), and a tendency existed for cardiovascular mortality (HR, 1.26; 95% CI, 0.97-1.63; P = 0.087), which seemed to be driven by fatal stroke (HR, 1.72; 95% CI, 1.17-2.54; P = 0.006) rather than cardiac mortality (HR, 0.67; 95% CI, 0.41-1.07; P = 0.094). The predictive value remained in 528 hypertensives for both all-cause (HR, 1.38; 95% CI, 1.13-1.69; P = 0.001) and cardiovascular (HR, 1.45; 95% CI, 1.07-1.96; P = 0.017) mortality, again driven by stroke. Our findings also remained significant after we excluded participants with macroalbuminuria, those on antihypertensive treatment, as well as participants who died within 1 year after enrollment. CONCLUSION In nondiabetic HIV-negative Africans, albuminuria predicts all-cause and stroke mortality.

Low testosterone and hyperkinetic blood pressure responses in a cohort of South African men: the SABPA study

Hypertension (HT) and the metabolic syndrome are major problems in Africa. The role of sex hormones in the cardiovascular profile of black Africans in South Africa has not been studied. Our objective was to study the association between the sex hormones and ambulatory blood pressure and the heart rate (HR) in black and white South Africans. The 24-hour ambulatory blood pressure measurements were performed and the blood samples were taken between 07:00 and 09:00 hours. A total of 80 black and 98 white South African teachers between 25 and 65 years of age from similar socioeconomic backgrounds from the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study were included. As a result, a more vulnerable cardiovascular profile was observed in Africans compared with Caucasians. In the African group, low testosterone (T) explained 19%–36% of the variance in systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR, whereas in the Caucasian group non-sex-hormone-binding globulin (non-SHBG)-bound T explained 27% of the variance in HR. In the African males, inverse associations between blood pressure and T (SBP: P = .08; DBP: P = .02) and non-SHBG-bound T (SBP: P < .001; DBP: P < .01) and HR (P < 0.01) were observed. Ambulatory HR predicted a prediabetic state in Africans. In conclusion, low T levels may predispose or result in impaired cardiovascular function in African men. The possibility exists that a prediabetic state, vagal-impaired HR, and hyperkinetic blood pressure responses may predispose or result in low T levels in African men.

Retinal vessel caliber and its relationship with nocturnal blood pressure dipping status: the SABPA study.

Adverse changes in retinal microvasculature caliber are associated with incident hypertension, coronary heart disease and stroke. The absence of a nocturnal dipping in arterial pressure may induce changes throughout the vascular tree, including the retinal microvasculature, but the later link is not sufficiently studied. We explored the relationship between retinal vessel caliber and dipping status in a group of black and white teachers. The study included black (n=68) and white (n=81) men (24–66 years) from the SABPA study. We measured 24 h ambulatory blood pressure and the percentage mean arterial pressure dipping(%MAPdip) was calculated as (diurnal MAP−nocturnal MAP)/diurnal MAP × 100. Retinal images were captured and the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) calculated. Black men demonstrated higher diurnal and nocturnal MAP (P⩽0.001) and a lesser %MAPdip compared with white men (P=0.047). When stratified by dipping status, black non-dippers (n=33) revealed an increased CRVE (P<0.001) compared with their dipper counterparts (n=35). In black men, CRVE was negatively (R2=0.38, β=−0.47, P<0.001) associated with %MAPdip independent of 24 h MAP or nocturnal MAP. CRVE also associated negatively with dipping status as a dichotomized variable (R2=0.29, β=−0.32, P=0.006), independent of 24 h MAP. These associations were absent in the white men. In conclusion, in this group of black men, a non-dipping blood pressure profile was associated with a larger CRVE, suggesting microvascular deterioration due to the absence of nocturnal dipping in blood pressure. This may add to our understanding of the stroke risk in black populations.