Carla M.T. Fourie

Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis

Background Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. Methods We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. Results Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, −0.59; 95% CI, −0.86 to −0.31), BMI (SMD, −0.32; 95% CI, −0.45 to −0.18), SBP (SMD, −0.40; 95% CI, −0.55 to −0.25) and DBP (SMD, −0.34; 95% CI, −0.51 to −0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, −0.34; 95% CI, −0.62 to −0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. Conclusions Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.

Blood glutathione and subclinical atherosclerosis in African men: the SABPA study

BACKGROUND Sub-Saharan Africans face an increasing burden of hypertension and related cardiac and cerebrovascular morbidity and mortality, making the identification of factors leading to early vascular abnormalities imperative. METHODS We investigated the possible influence of the antioxidant glutathione (GSH) on early subclinical atherosclerosis in 63 hypertensive (aged 45.2 years) and 34 normotensive (aged 38.9 years; P < 0.001) nondiabetic African men. We measured ambulatory daytime systolic and diastolic blood pressure (SBP, DBP) as well as daytime mean arterial pressure (MAP), carotid intima-media thickness (CIMT), and calculated the cross-sectional wall area. We determined the reduced form of GSH in whole blood and blood glucose in serum. RESULTS Blood glucose (110 vs. 92 mg/dl; P < 0.001) and CIMT (0.75 vs. 0.61 mm; P < 0.001) were higher in hypertensives compared to normotensives. No significant difference existed for GSH. Associations in normotensives suggested the hypotensive effect of GSH after single (SBP: r = -0.35, P < or = 0.05; DBP: r = -0.37, P < or = 0.05; MAP: r = -0.38, P < or = 0.05) and multiple (SBP: B = -0.015, P < 0.05; DBP: B = -0.011, P < 0.05; MAP: B = -0.012, P < 0.05) regression analyses. In hypertensives, CIMT (B = -0.00027, P < 0.01) and cross-sectional wall area (CSWA) (B = -0.0066, P < 0.05) correlated negatively with GSH. These findings were consistent after excluding 10 human immunodeficiency virus (HIV)-positive hypertensive subjects. CONCLUSIONS In hypertensive African men, CIMT is negatively associated with GSH, suggesting a possible contributory role of attenuated GSH levels in the development of subclinical atherosclerosis.

Dimethylarginines: Their vascular and metabolic roles in Africans and Caucasians

OBJECTIVE Alarming increases in hypertension and type 2 diabetes among Africans accentuate the need to identify factors that could serve as targets for prevention or treatment. In Caucasian populations, asymmetric dimethylarginine (ADMA), the predominant endogenous nitric oxide synthase inhibitor, is associated with cardiovascular disease and insulin resistance (IR). ADMAs counterpart, symmetric dimethylarginine (SDMA), originally thought to be inert, was recently also linked with cardiovascular risk. Since little information regarding ADMA or SDMA is available for Africans, our aim was to explore the relationships of ADMA and SDMA with measures of arterial stiffness and IR in Africans and Caucasians from South Africa. METHODS The study consisted of 235 nonsmoking, nondiabetic, nonobese, human immunodeficiency virus-uninfected Africans (n=64) and Caucasians (n=171), aged 20-70 years. We measured blood pressure, pulse wave velocity, ADMA, SDMA, and IR (homeostasis model assessment, HOMA). RESULTS African and Caucasian men had similar ADMA and SDMA, whereas Caucasian women had higher ADMA and SDMA than African women (P<0.05). African men and Caucasian women indicated strong correlations of ADMA with arterial stiffness (r=0.47, P=0.021; r=0.26, P=0.008), confirmed in multivariate analyses. Caucasian participants showed negative associations between SDMA and HOMA, being strongest in the men (r=-0.41; P=0.002). CONCLUSION Our results indicate that ADMA is independently associated with vascular dysfunction in African men and Caucasian women. A strong, independent negative association of SDMA with IR was found only in Caucasian participants. The molecular explanation for this is unclear, but these findings motivate experimental studies that could shed more light on these relationships.

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.

Psychological Distress and the Development of Hypertension Over 5 Years in Black South Africans

Alarming increases in the incidence of hypertension in many low‐ and middle‐income countries are related to alcohol overuse. It is unclear whether alcohol overuse is a symptom of psychological distress. The authors assessed psychological distress in Africans and its relationship with a 5‐year change in blood pressure (BP), independent of alcohol intake. The authors followed 107 Africans with optimal BP (≤120/80 mm Hg) (aged 35–75 years) over 5 years. Alcohol intake (self‐report and serum γ‐glutamyl transferase) and nonspecific psychological distress (Kessler Screening Scale for Psychological Distress [K6]) were assessed. The K6 predicted hypertension development (P=.019), and its individual component “nervous” increased a participants risk two‐fold to become hypertensive (hazard ratio, 2.00 [1.23–3.26]). By entering K6 and γ‐glutamyl transferase into multivariable‐adjusted regression models for change in systolic BP, both were independently associated with change in systolic BP. Psychological distress and scoring high on being nervous predicted the development of hypertension over 5 years, independent of alcohol intake.

The association of 25(OH)D with blood pressure, pulse pressure and carotid-radial pulse wave velocity in African women.

High susceptibility of the African population to develop cardiovascular disease obliges us to investigate possible contributing risk factors. Our aim was to determine whether low 25(OH)D status is associated with increased blood pressure and carotid-radial pulse wave velocity in black South African women. We studied 291 urban women (mean age: 57.56±9.00 yrs.). 25(OH)D status was determined by serum 25(OH)D levels. Women were stratified into sufficient (>30 ng/ml), and insufficient/deficient (<30 ng/ml) groups. Cardiovascular variables were compared between groups. Women with low 25(OH)D levels had significantly higher SBP (150.8±27.1 vs. 137.6±21.0), DBP (94.7±14.5 vs. 89.3±12.3) and PP (53.15(50.7;55.7) vs. 46.3(29.4;84.6)) compared to women with sufficient levels. No significant difference was observed with regards to c-rPWV. ANCOVA analyses still revealed significant differences between the two groups with regards to SBP, DBP as well as PP. Partial correlations revealed significant inverse association between SBP and 25(OH)D (p = .04;r = −.12). Women with low 25(OH)D levels were ∼2 times more likely to have high SBP (95% CI: 3.23;1.05). To conclude, women with deficient/insufficient 25(OH)D had significantly higher SBP compared to women with a sufficient 25(OH) status.

Associations of suPAR with lifestyle and cardiometabolic risk factors

Soluble urokinase plasminogen activator receptor (suPAR), a novel indicator of low‐grade inflammation, is associated with cardiovascular disease and mortality in the general population, while an unhealthy lifestyle influences inflammatory status. We aimed to explore the relationship of suPAR with lifestyle and cardiometabolic risk factors in a black South African population.

Ion selectivity of scorpion toxin-induced pores in cardiac myocytes

The lytic activity of parabutoporin (PP) and opistoporin 1 (OP1) on mammalian and bacterial membranes have been described. We investigated pore-formation and ion selectivity in cardiac myocytes by measuring the whole cell leak current by means of the patch clamp technique. Pore formation was observed as the induction of leak currents. Ion selectivity of the pores was indicated by the shift of the reversal potential (E(rev)) upon substitution of intra- and extra-cellular ions. Results were compared with the effect of gramicidin A (gramA). PP and OP1 induced a fluctuating leak current and indicate non-selectivity of PP-induced pores. PP- and OP1-induced pores are between 1.38 and 1.78 nm in diameter.

The association of oxidative stress with arterial compliance and vascular resistance in a bi-ethnic population: the SABPA study.

Abstract A loss of arterial elasticity increases the risk for cardiovascular events. Oxidative injury to the vessel wall may be one of the underlying mechanisms influencing arterial elasticity. We compared markers of oxidative stress, antioxidant capacity, inflammation, windkessel compliance (Cwk), and total peripheral resistance (TPR) in black and white South Africans. Associations of arterial compliance and vascular resistance (as indicated by TPR) with oxidative stress, antioxidant capacity and inflammatory markers were also investigated. We included 146 black and 181 white men and women. Measurements from the Finometer device were used to calculate Cwk and TPR while thiobarbituric acids reactive substances (TBARS), glutathione peroxidase (GPx), C-reactive protein (CRP), and interleukin-6 (IL-6) were analyzed in serum or urine samples. Black participants had higher TPR, TBARS, GPx, CRP, and IL-6 levels (all p ≤ 0.018) and lower Cwk (both p ≤ 0.013) compared to white participants. Multiple regression analyses revealed independent associations of Cwk (β = −0.27, p = 0.015) and TPR (β = 0.18, p = 0.018) with TBARS in black participants, while Cwk (β = −0.10; p = 0.019) and TPR (β = 0.13, p = 0.047) were independently associated with GPx in white participants. Decreased arterial compliance and increased vascular resistance associated with increased oxidative damage independent of hypertensive status in black participants. These results suggest that oxidative stress plays a role in early vascular changes in a black population prone to the development of cardiovascular disease.

Soluble urokinase plasminogen activator receptor and hypertension among black South Africans after 5 years

Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker that links inflammation with cardiovascular risk. However, studies linking suPAR and hypertension are scant. First, we determined whether baseline suPAR is elevated in normotensive black South Africans who developed hypertension over 5 years, compared with those who remained normotensive; and second, whether hypertension is associated with suPAR. This substudy is embedded in the South African leg of the Prospective Urban and Rural Epidemiology study, performed in the North West Province. We investigated 429 normotensive individuals, of which 191 developed hypertension and 238 remained normotensive over 5 years. We determined suPAR from plasma (ethylenediaminetetraacetic acid) samples with the suPARnostic ELISA Kit and blood pressure with an OMRON HEM-757 device. Despite similar mean baseline suPAR levels (P=0.43), suPAR increased more in the group that developed hypertension compared with those who remained normotensive (14.2% vs. 6.94%; P=0.007). Five-year percentage change in systolic blood pressure correlated positively (r=0.23; P=0.002) and associated independently with baseline suPAR (β=0.14; P=0.043), only in participants who developed hypertension. Participants were 1.41 times more likely (P=0.015) to develop hypertension with 1 s.d. increase in percentage change in suPAR levels over 5 years. Change in systolic blood pressure was associated with baseline suPAR in hypertensive participants and change in suPAR with hypertensive status. This study highlights the need for more research on the role of suPAR in hypertension and cardiovascular disease development in black South Africans.