Lack of impact of HIV status on carotid intima media thickness in a cohort of stroke patients in South Africa.

INTRODUCTION: People living with HIV (PLWH) are at increased risk for cardiovascular disease. Carotid intima media thickness (cIMT) is a validated surrogate marker of atherosclerosis, and an accurate predictor of future cardiovascular events. It is uncertain whether HIV potentiates stroke risk through atherosclerosis in Sub-Saharan Africa and what effect HIV status has on cIMT. We sought to investigate the relationship between HIV status and cIMT in stroke patients in a region that is burdened with dual epidemics of HIV and stroke in the young. METHODS: Consecutive patients with new onset ischaemic stroke were recruited from a quaternary-level hospital in Johannesburg, South Africa, from August 2014 to November 2017. Patients were assessed for the presence of traditional cardiovascular risk factors and HIV infection, and investigated for stroke aetiology. cIMT was measured using high resolution B-mode ultrasound following standardized techniques. RESULTS: 168 patients were included in the study, of which 62 (36.9%) were PLWH. Mean cIMT was higher in HIV-uninfected patients when compared to PLWH (0.79 ± 0.19 mm vs 0.69 ± 0.18 mm, p = 0.0021). However after adjusting for age, sex, hypertension, diabetes mellitus, smoking, total cholesterol, body mass index and stroke aetiology, there was no difference in mean cIMT between the groups (0.76 ± 0.16 mm vs 0.73 ± 0.17 mm, p = 0.29). Regression models revealed the determinants of cIMT to be age (p < 0.0001), hypertension (p = 0.0098) and total cholesterol (p = 0.005), while the determinants of increased cIMT (≥0.70 mm) were only age (p < 0.0001) and hypertension (p = 0.0002). CONCLUSION: HIV status had no effect on cIMT in our cohort of stroke patients. The main determinants of cIMT were age and hypertension.

Cardioembolic stroke in an HIV endemic region: underdiagnosed and severe.

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.

Southern African HIV Clinicians Society Guideline for the clinical management of syphilis.

Syphilis, 'the great imitator', caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV.

Stroke, HIV and the Immune Reconstitution Inflammatory Syndrome in the absence of opportunistic infections.

INTRODUCTION: Stroke in people living with HIV (PLWH) has been described to occur soon after the initiation of antiretroviral therapy (ART) possibly related to the Immune Reconstitution Inflammatory Syndrome (IRIS). We sought to investigate whether there was a temporal association between stroke and recent ART initiation in the absence of opportunistic infections (OIs), and to identify risk factors for this. METHODS: This cross-sectional study recruited PLWH with new-onset stroke at a hospital in Johannesburg, South Africa, from 2014 to 2017, excluding all patients with OIs. Patients were assessed for ART duration, CD4 count, HIV viral load, inflammatory markers and cardiovascular risk factors. RESULTS: 77 PLWH were recruited, of which 35 were on ART at the time of stroke. Of the patients with confirmed ART duration (n = 28), 9 (32.1%) had a stroke within the first 6 months of starting ART (crude incidence rate of 0.73 cases per patient year). In the period beyond 6 months, 19 strokes occurred (crude incidence rate of 0.21 cases per patient year), translating to a 3.5 times greater risk in the first 6 months (p = 0.0002). There were no clearly identified risk factors when comparing those who had strokes in the first 6 months to those after 6 months and ART-naïve patients. CONCLUSION: Almost a third of strokes in PLWH may be related to IRIS, with a crude incidence rate 3.5 times higher in the first 6 months following ART-initiation compared to beyond 6 months. This appears to be independent of OIs. Risk factors are unclear.

Stroke as the index presentation of traditional cardiovascular risk factors and Human Immunodeficiency Virus in a South African population.

OBJECTIVES: We sought to identify what proportion of each cardiovascular risk factor and Human Immunodeficiency Virus (HIV) was first diagnosed at the time of stroke, compared to those that were diagnosed prior to the event, and to explore if this had any impact on the severity of stroke. METHODS: Adult patients presenting with a new stroke to a quaternary hospital in Johannesburg between 2014 and 2017 were prospectively recruited. Patients were investigated for undiagnosed traditional cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidaemia, atrial fibrillation, obesity and smoking), as well as HIV infection. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). RESULTS: 346 patients were included. Stroke was the index presentation for at least one risk factor in 199 (57.5 %) patients. Dyslipidaemia was newly diagnosed in 76.0 % of all dyslipidaemics (95 out of 125). Newly-diagnosed dyslipidaemia was associated with a more severe neurological deficit (Median NIHSS of 12 (8-16) vs 7 (4-12), p=0.0007) and younger age on presentation (53 (44-63) years vs 62 (51-71) years, p=0.02) as compared to previously-diagnosed dyslipidaemia. CONCLUSIONS: More than half of patients had previously undiagnosed modifiable risk factors at the time of their stroke. Dyslipidaemia was undiagnosed in a very high proportion, and this was associated with a higher stroke severity and younger age of presentation.

Proximal aortic stiffness modifies the relationship between heart rate and backward wave and hence central arterial pulse pressure.

Aims: A lower heart rate (HR) increases central blood pressure through enhanced backward wave pressures (Pb). We aimed to determine whether these relationships are modified by increases in aortic stiffness. Methods: Using non-invasive central pressure, aortic velocity and diameter measurements in the outflow tract (echocardiography), we assessed the impact of aortic stiffness on relationships between HR and arterial wave morphology in 603 community participants < 60 years of age, 221 ≥ 60 years, and in 287 participants with arterial events [stroke and critical limb ischemia (CLI)]. Results: As compared to community participants < 60 years, those ≥ 60 years or with events had increased multivariate adjusted proximal aortic characteristic impedance (Zc) and carotid femoral pulse wave velocity (PWV) (p < 0.05 to < 0.0001). Community participants ≥ 60 years and those with events also had a greater slope of the inverse relationship between HR and Pb (p < 0.001 for comparison). While in community participants < 60 years, no interaction between indexes of aortic stiffness and HR occurred, in those ≥ 60 years (p < 0.02) and in those with arterial events (p = 0.001), beyond aortic root diameter, an interaction between Zc and HR, but not between PWV and HR independently associated with Pb. This translated into stepwise increases in the slope of HR-Pb relationships at incremental tertiles of Zc. Although HR was inversely associated with the systemic reflection coefficient in community participants ≥ 60 years (p < 0.0001), adjustments for the reflection coefficient failed to modify HR-Pb relations. Conclusion: Beyond the impact on systemic wave reflection, increases in proximal aortic stiffness enhance the adverse effects of HR on Pb and hence central BP.

Optic neuritis: A South African hospital-based prospective study protocol.

BACKGROUND: Optic neuritis is a relatively common disease with an estimated lifetime risk of 0.6 per 1000; the estimated prevalence is 1-5 per 100 000/year. It occurs because of inflammation of the optic nerve from a variety of causes. The diagnosis of the disorder is established clinically and current literature is predominantly based on white patients from high-income countries. Optic neuritis presents differently in black patients compared to white patients. This study aims to assess the presentation and outcome of optic neuritis patients in a South African setting. METHODS: This is a prospective, hospital-based cohort study that will enrol patients with optic neuritis presenting to either the neurology department at Chris Hani Baragwanath Academic Hospital or the ophthalmology department at St John Eye Hospital, both in Johannesburg, South Africa. The specific aetiologies, clinical presentation and radiological findings will be studied, and the patient's course over one year will be documented in three-monthly follow-up visits. A specific group of patients with Neuromyelitis Optica Spectrum Disorders (NMOSD) and Myelin Oligodendrocyte Glycoprotein Associated Disorders (MOGAD) optic neuritis will be followed up for 5 years at yearly intervals. DISCUSSION: This study represents one of the few cohort studies in Sub-Saharan Africa that seeks to investigate optic neuritis. Our hope is that it will lead to better insights regarding the presentation, course and outcome of this condition. We will also analyse the data with a view of developing a predictive model for good visual outcome.

Relations of aortic stiffness with arterial damage beyond brachial pressure are both dependent and independent of central arterial pulsatile load.

AIM: We aimed to determine whether the impact of aortic stiffness on atherosclerotic or small vessel end organ damage beyond brachial blood pressure depends in-part on stiffness-induced increases in central arterial pressures produced by an enhanced resistance to flow (characteristic impedance, Zc). METHODS: We studied 1021 participants, 287 with stroke or critical limb ischaemia, and 734 from a community sample with atherosclerotic or small vessel end organ measures. Central arterial haemodynamics were determined from arterial pressure (SphygmoCor) and velocity and diameter assessments in the outflow tract (echocardiography). RESULTS: Although Zc and carotid-femoral pulse wave velocity (PWV) were correlated (P < 0.0001), these relations were not independent of confounders (P = 0.90). Both Zc and hence central arterial pressures generated by the product of Zc and aortic flow (Q) (PQxZc), as well as PWV were independently associated with carotid intima-media thickness, estimated glomerular filtration rate (eGFR), endothelial activation markers [vascular cell adhesion molecule-1 (V-CAM-1)] and events. With further adjustments for brachial pulse pressure (PP) or SBP, PWV and PQxZc were both associated with eGFR and V-CAM-1. Relationships between PWV and eGFR or V-CAM-1 were independent of PQxZc (P < 0.05) and relationships between PQxZc and eGFR and V-CAM-1 were independent of PWV (P < 0.005). Similarly, with adjustments for confounders and brachial PP or SBP, across the full adult lifespan, both aortic PWV and PQxZc were increased in those with arterial events (P < 0.005). Relationships between PWV and events were again independent of PQxZc (P < 0.005) and between PQxZc and events were independent of PWV (P < 0.0001). CONCLUSION: Beyond brachial blood pressure, the impact of aortic stiffness on arterial damage involves effects that are both dependent (proximal aortic Zc and hence PQxZc) and independent (full aortic length indexed by PWV) of central arterial pulsatile load. Hence, PWV and brachial PP may be insufficient to account for all of the damage mediated by increases in aortic stiffness.

Marked Arterial Functional Changes in Patients With Arterial Vascular Events Across the Early Adult Lifespan.

OBJECTIVE: The age at which arteriosclerosis begins to contribute to events is uncertain. We determined, across the adult lifespan, the extent to which arteriosclerosis-related changes in arterial function occur in those with precipitous arterial events (stroke and critical limb ischemia). Approaches and Results: In 1082 black South Africans (356 with either critical limb ischemia [n=238] or stroke [n=118; 35.4% premature], and 726 age, sex, and ethnicity-matched randomly selected controls), arterial function was evaluated from applanation tonometry and velocity and diameter measurements in the outflow tract. Compared with age- and sex-matched controls, over 10-year increments in age from 20 to 60years, multivariate-adjusted (including steady-state pressures) aortic pulse wave velocity, characteristic impedance (Zc), forward wave pressures (Pf), and early systolic pulse pressure amplification were consistently altered in those with arterial events. Increases in Zc were accounted for by aortic stiffness (no differences in aortic diameter) and Pf by changes in Zc and not aortic flow or wave re-reflection. Multivariate-adjusted pulse wave velocity (7.48±0.30 versus 5.82±0.15 m/s, P<0.0001), Zc (P<0.0005), and Pf (P<0.0001) were higher and early systolic pulse pressure amplification lower (P<0.0001) in those with precipitous events than in controls. In comparison to age- and sex-matched controls, independent of risk factors, pulse wave velocity, and Zc (P<0.005 and <0.05) were more closely associated with premature events than events in older persons and Pf and early systolic pulse pressure amplification were at least as closely associated with premature events as events in older persons. CONCLUSIONS: Arteriosclerosis-related changes in arterial function are consistently associated with arterial events beyond risk factors from as early as 20 years of age.

Complementary Impact of Carotid Intima-Media Thickness With Plaque in Associations With Noncardiac Arterial Vascular Events.

The ability of carotid intima-media thickness (IMT) to predict risk beyond plaque is controversial. In 952 participants (critical limb ischemia [CLI] or stroke, n = 473; community, n = 479), we assessed whether relationships with events for IMT complement the impact of plaque in young patients depending on the extent of thrombotic versus atherosclerotic disease. The extent of atherosclerotic versus thrombotic occlusion was determined in 54 patients with CLI requiring amputations. Thrombotic occlusion in CLI was associated with younger age (P < .0001) and less plaque (P = .02). Independent relations between plaque and CLI were noted in older (>50 years; P < .005 to <.0001) but not younger (P > .38) participants, while independent relations between plaque and stroke (P < .005 to <.0001) and between IMT and CLI (P < .0001) were noted in younger participants. Although in performance (area under the receiver operating curve) for event detection, IMT thresholds failed to add to plaque alone in older patients (0.680 ± 0.020 vs 0.664 ± 0.017, P = .27), IMT improved performance for combined stroke and CLI detection when added to plaque in younger patients (0.719 ± 0.023 vs 0.631 ± 0.026, P < .0001). Because in younger participants the high prevalence of thrombotic occlusion in CLI is associated with less plaque, IMT adds information in associations with arterial vascular events.

Carotid intima-media thickness, but not chronic kidney disease independently associates with noncardiac arterial vascular events in South Africa.

AIM: Although chronic kidney disease (CKD) as determined from estimated glomerular filtration rate (eGFR) is recommended for risk prediction by current hypertension guidelines, the equations to derive eGFR may not perform well in black Africans. We compared whether across the adult lifespan, eGFR or CKD are as closely associated with noncardiac arterial vascular events, as carotid intima-media thickness (IMT), in Africa. METHODS: In 1152 black South Africans [480 with noncardiac arterial events (294 with critical lower limb ischemia, 186 with stroke) of which 37% were premature] and 672 age, sex and ethnicity-matched controls from a randomly selected community sample, we assessed relations between eGFR, CKD or carotid IMT (B-mode ultrasound) and arterial events. RESULTS: From 20 years until old age, with or without adjustments, IMT was increased in those with as compared with without events (P < 0.01 at each decade of age). However, at any decade of age across the adult lifespan neither creatinine concentrations, nor eGFR were altered in those with arterial events (P > 0.28). Although IMT was strongly and independently associated with the odds of an event [odds ratio per 1 SD (0.171 mm) effect = 2.19, confidence interval = 1.75-2.78, P < 0.0001], neither creatinine concentrations (P = 0.89), modification of diet in renal disease-derived (P = 0.07), nor Chronic Kidney Disease Epidemiology Collaboration-derived [odds ratio per 1 SD (22.5 ml/min per 1.73 m) effect = 1.06, confidence interval = 0.89-1.27, P = 0.51] eGFR were independently associated with the odds of an event. Although many with premature events had an increased IMT (63%), few with either premature events (8%) or with events at an older age (21%) had CKD and CKD had a poor performance (0.539 ±â€Š0.011) and low sensitivity (16%) for event detection. CONCLUSION: In black South Africans, despite carotid IMT strongly associating with noncardiac arterial vascular events (stroke and critical lower limb ischaemia) consistently across the adult lifespan, few with events have CKD and CKD fails to associate with events.