Angela Jill Woodiwiss

Cardiovascular events occur 20 years earlier in Sub-Saharan Africa compared to Europe. The risk factors for atherosclerosis differ between population groups and according to age. We compared the main correlates of carotid intima-media thickness (IMT, an index of atherosclerosis) in young and older adults of African ancestry. Hemodynamic (central and peripheral arterial pressures) and metabolic factors (lipids, glucose, glycated haemoglobin), smoking status and carotid IMT were determined in 573 adult Africans. In young (age<35years, n = 181) and middle-aged (35–59years, n = 231) adults, carotid IMT was associated with hemodynamic and metabolic cardiovascular risk factors on bivariate analyses. In older (age≥60years, n = 161) adults only hemodynamic factors were associated with carotid IMT. After adjustments for confounders, lipids were not associated with carotid IMT at any adult age. Carotid IMT was independently associated with backward wave pressure (Pb, p = 0.001) and age (p = 0.006) in young adults; with hemodynamics (central systolic blood pressure, p = 0.003; Pb, p = 0.02), age (p = 0.0002), body mass index (BMI, p = 0.005) and heart rate (p = 0.007) in middle-aged adults; and with Pb (p < 0.0001), male sex (p = 0.03), and HR (p = 0.04) in older adults. Increased carotid IMT was related to Pb in young (odds ratio [OR] = 1.233, p = 0.0003) and older (OR = 1.086, p = 0.0059) adults, and BMI (OR = 1.089, p = 0.0005) in middle-aged adults. Improvements in predictive performance for detecting increased carotid IMT were shown with Pb in young (p = 0.0032) and older (p = 0.0031) adults, and with BMI (p = 0.0004) in middle-aged adults. In conclusion, in African adults in Sub-Saharan Africa, carotid IMT is associated with hemodynamic factors, but not lipids. Moreover, in young adults, carotid IMT is primarily associated with hemodynamic factors.

Aims: A distinct volume-dependent increase in systemic blood flow has recently been demonstrated to contribute to hypertension in groups of African ancestry. We determined whether systemic blood flow contributes to resistant or refractory hypertension (RHTN). Methods: We compared the multivariate adjusted haemodynamic correlates of blood pressure in RHTN (n = 100) on diuretic and other therapy, to those in age and sex-matched normotensives (NT, n = 128), untreated hypertensives (Untreat-HTN, n = 124), and treated-controlled hypertensives (Control-HTN, n = 74) of African ancestry in South Africa. Haemodynamics were determined from velocity and diameter measurements in the left ventricular outflow tract, and central arterial pressures. Results: All hypertensives had higher stroke volume (SV), cardiac output (CO) and peak aortic flow (Q) compared to NT (P < 0.05 to P < 0.0001). Proximal aortic characteristic impedance (Zc) in RHTN was similar to Untreat-HTN, but greater than NT (P < 0.005), and Control-HTN (P < 0.05). In RHTN, systemic vascular resistance was lower compared NT, Untreat-HTN and Control-HTN (P < 0.005 to P < 0.02 to QxZc) and hence aortic pulse pressure were higher in RHTN compared to NT, Untreat-HTN and Control-HTN (P < 0.0001), effects attributed primarily to increases in SV and Q. Conclusions: Despite the use of diuretic therapy, increases in systemic blood flow are the main determinant of RHTN in groups of African ancestry in South Africa. Novel approaches to targeting volume-dependent increases in blood flow in this population are therefore required.

Background: Whether coronary artery disease (CAD) associates with proximal aortic stiffness-induced increases in central arterial forward wave pressures (Pf), but not peak central arterial pulse pressure (PPc) beyond peripheral PP, is uncertain. Therefore, we aimed to investigate the relationship between CAD and aortic characteristic impedance (Zc) and Pf beyond brachial PP and PPc. Methods: From central pressure (SphygmoCor), and aortic velocity and diameter measurements (echocardiography), we compared Zc (n = 71) and central arterial pressure wave morphology (n = 189) in patients with CAD, to 210 age- and sex-matched controls, and patients with stroke or critical limb ischemia (CLI) (n = 287). Results: With adjustments for confounders, including mean arterial pressure and aortic root diameter, Zc was increased in patients with CAD compared to controls and patients with stroke or CLI (P < 0.0001). The early systolic pressures generated by the product of peak aortic flow (Q) and Zc (P_QxZc), and Pf were also increased in patients with CAD compared to controls and patients with alternative arterial diseases (P < 0.0005). Enhanced P_QxZc at peak PPc, rather than increases in re-reflected wave pressures, accounted for increases in Pf. After further adjustments for brachial PP or SBP, the higher Pf values in patients with CAD were retained (P < 0.01 to P < 0.0005). In contrast, although peak PPc was higher in patients with CAD or alternative arterial diseases compared to controls (P < 0.05 to P < 0.0005), these differences were abolished by further adjustments for brachial BP. Conclusion: Increases in stiffness-associated proximal aortic Zc in patients with CAD translate into increases in Pf, but not peak PPc, beyond brachial BP. Hence, the pulsatile load responsible for CAD is beyond brachial BP and poorly indexed by PPc.

Objective: Various insulin resistance (IR) indices have been developed to assess cardiovascular (CVS) risk. We compared the association between ten IR indices and cardiac, renal, and vascular end-organ measures in a predominantly young (age 45.0 ± 18.3 years) South African Black population. Methods: We assessed the relationships between ten IR indices (homeostatic model assessment for IR [HOMA-IR], quantitative insulin sensitivity check index [QUICKI], metabolic score for IR [METS-IR], triglyceride–glucose index [TyG], TyG–body mass index [TyG-BMI], TyG–waist circumference [TyG-WC], TyG–waist-to-height ratio [TyG-WHtR], triglyceride to high-density cholesterol concentration [TyG-HDL], lipid accumulation product [LAP], visceral adiposity index [VAI]) and end-organ measures in 779 community participants of African ancestry. Results: HOMA-IR and QUICKI were the only IR indices consistently associated with end-organ measures (left ventricular [LV] mass index, p ≤ 0.005; LV relative wall thickness, p < 0.0001; early-to-late mitral velocity, p ≤ 0.01; E/e’, p ≤ 0.002; e’, p < 0.0001; pulse wave velocity, p = 0.036 (HOMA-IR only); glomerular filtration rate [GFR], p < 0.0001), independent of confounders. Furthermore, HOMA-IR was consistently higher, and QUICKI lower, in those with compared to those without end-organ damage (LV hypertrophy [p ≤ 0.03], concentric LV [p < 0.03], and reduced GFR [p ≤ 0.008]), independent of confounders. Importantly, the associations between HOMA-IR or QUICKI and end-organ measures were independent of additional CVS risk factors, including adiposity measures, and were replicated in the participants without diabetes mellitus (n = 669) and in the participants without high blood pressure (n = 505). Conclusions: In a predominantly young community of African ancestry, of ten recommended IR indices, only HOMA-IR and QUICKI were consistently associated with end-organ damage independent of CVS risk factors.

The May Measurement Month (MMM) campaign was carried out in South Africa in 2022 with the aim of raising awareness of raised blood pressure (BP). Here, we report on the findings of the campaign. Adults aged ≥18 years were recruited opportunistically at university campuses, community centres, schools, sport complexes, public parks, shopping centres, hospitals, and through household visits. Three seated BP readings were taken for each participant, along with completion of a questionnaire on demographics, lifestyle factors, and comorbidities. Hypertension was defined as a systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or being on antihypertensive medication. Controlled BP was defined as being on antihypertensive medication with a BP < 140/90 mmHg. Multiple imputation was used to estimate any missing BP readings. In total, 4602 were screened, with a mean age of 31.9 years and 61.9% of whom were female. Of all participants, 1217 (26.5%) had hypertension, of whom 456 (37.5%) were aware, and 406 (33.4%) were on antihypertensive medication. Of those on antihypertensive medication, 205 (50.5%) had controlled BP, and of all participants with hypertension, 16.8% had controlled BP. The MMM campaign in South Africa identified significant numbers of participants with either untreated or inadequately treated hypertension. The high prevalence of hypertension, despite the young adult age, together with the high proportions of individuals unaware of their hypertension and with uncontrolled BP highlights the need for hypertension screening and awareness campaigns, and more rigorous management of hypertension.

Objective: The study aimed to assess the potential impacts of mean arterial pressure (MAP) and its determinants (cardiac output and systemic vascular resistance) on diabetic nephropathy (DNP)-associated impaired aortic function. Methods: This multi-ethnic study included 115 chronic kidney disease (CKD) patients (67 non-dialysis and 48 dialysis). Six aortic function measures were evaluated by SpygmoCor. The stroke volume was determined by echocardiography. Results: Hypertensive nephropathy (HNP) (53.9%), DNP (32.2%), glomerulonephritis (19.1%), and HIV-associated nephropathy (7.8%) composed the major CKD etiologies. Concurrent HNP and DNP were present in 31.1% of the patients. Participants with compared with those without concurrent HNP and DNP experienced more frequent established cardiovascular disease (43.2% versus 14.9%, p = 0.01), a faster pulse wave velocity (p = 0.001), and smaller total arterial compliance as an indicator of proximal aortic stiffness (p = 0.03). DNP was associated with each aortic function measure (p < 0.001–0.02) independent of potential confounders and MAP, as well as its determinants. HNP was not related to aortic function (p > 0.05 for all relationships). MAP and its determinants did not mediate the potential impact of DNP on aortic function (−4.1–6.4% contribution). Covariates that were associated with impaired aortic function measures included MAP and its determinants (p < 0.001–0.01). Conclusions: Mean or distending arterial pressure and its determinants were associated with impaired aortic function in the overall CKD population. However, these hemodynamic factors did not mediate DNP-associated impaired aortic function. Our results suggest that blood pressure lowering can be anticipated to improve impaired aortic function in the overall CKD population but not when it is solely induced by DNP.

Carotid artery intima-media thickness (IMT), an important clinical marker of atherosclerosis, is used widely in screening for cardiovascular risk and prognosis. Measurements of carotid artery IMT are made on both the left and right sides of the body, however as per the Mannheim consensus, an average of these measurements is usually reported. Nevertheless, there is considerable debate whether there are side differences in the carotid artery IMT in terms of both measurements and determinants. In a large sample of Caucasian patients (n = 1888) referred for cardiovascular risk assessment, we compared the left and the right common carotid artery IMT measurements, and assessed whether age, gender and cardiovascular risk factors have differential effects. We found that the left common carotid artery IMT (0.7141 ± 0.1733 mm) is larger than the right (0.6861 ± 0.1594, p < 0.0001), but not in the young (< 30 years) or the elderly (> 69 years), and that this side difference is less in women (0.019 ± 0.116 mm) than in men (0.036 ± 0.148 mm, p < 0.001). In addition to age (p < 0.0001) and gender (p < 0.0001), the left common carotid artery IMT was determined by dyslipidaemia (protective, p = 0.016) and diabetes mellitus (p = 0.022); whereas the right common carotid artery IMT was determined by hypertension (p = 0.0002). The differential determinants of left versus right common carotid artery IMT were similar in men and women, and in young and old. In conclusion, side differences in measurements of the common carotid artery IMT depend upon age and gender. In addition, cardiovascular risk factors have differential effects on the left and right common carotid artery IMT.

Background and objectives Cardioembolic stroke (CES) appears to be a rare cause of stroke (4%–9%) in people living with HIV (PLWH) in sub-Saharan Africa (SSA). However, due to limited access to diagnostic resources, this may be an underestimate. It is also unclear which cardiac pathologies are the major contributors to CES in this region. We sought to determine the prevalence and aetiology of CES in PLWH and to determine whether there are any differences compared with HIV negative stroke patients. Methods This cross-sectional study recruited PLWH with new-onset stroke at a quaternary-level hospital in Johannesburg, South Africa, from 2014 to 2017, and compared them to age-matched and sex-matched HIV negative stroke patients. Comprehensive investigations were performed to determine the underlying stroke aetiology, including electrocardiography, echocardiography, CT angiography and cerebrospinal fluid examination. Results 85 PLWH with ischaemic stroke were recruited and compared with 109 HIV negative controls. CES was identified in 17/85 (20.0%) of PLWH. These patients had more severe strokes than PLWH with non-CES (National Institutes of Health Stroke Scale score 14.9±6.7 vs 11.7±5.4, p=0.04). Cardiomyopathy was the predominant cardiac pathology in PLWH (76.4% vs 45.5% in HIV negative, p=0.04) while valvulopathy was more common in HIV negative patients (42.4% vs 11.8% in PLWH, p=0.03). Arrhythmia (n=1) and ischaemic heart disease (n=1) were uncommon in PLWH. Conclusion CES is underdiagnosed in SSA and is more severe than non-CES. The identification of cardiomyopathy as the predominant underlying cardiac pathology may assist to target resources towards its detection using accessible cost-effective biomarkers.