In 2015, the United Nations set important targets to reduce premature cardiovascular disease (CVD) deaths by 33% by 2030. Africa disproportionately bears the brunt of CVD burden and has one of the highest risks of dying from non-communicable diseases (NCDs) worldwide. There is currently an epidemiological transition on the continent, where NCDs is projected to outpace communicable diseases within the current decade. Unchecked increases in CVD risk factors have contributed to the growing burden of three major CVDs—hypertension, cardiomyopathies, and atherosclerotic diseases- leading to devastating rates of stroke and heart failure. The highest age standardized disability-adjusted life years (DALYs) due to hypertensive heart disease (HHD) were recorded in Africa. The contributory causes of heart failure are changing—whilst HHD and cardiomyopathies still dominate, ischemic heart disease is rapidly becoming a significant contributor, whilst rheumatic heart disease (RHD) has shown a gradual decline. In a continent where health systems are traditionally geared toward addressing communicable diseases, several gaps exist to adequately meet the growing demand imposed by CVDs. Among these, high-quality research to inform interventions, underfunded health systems with high out-of-pocket costs, limited accessibility and affordability of essential medicines, CVD preventive services, and skill shortages. Overall, the African continent progress toward a third reduction in premature mortality come 2030 is lagging behind. More can be done in the arena of effective policy implementation for risk factor reduction and CVD prevention, increasing health financing and focusing on strengthening primary health care services for prevention and treatment of CVDs, whilst ensuring availability and affordability of quality medicines. Further, investing in systematic country data collection and research outputs will improve the accuracy of the burden of disease data and inform policy adoption on interventions. This review summarizes the current CVD burden, important gaps in cardiovascular medicine in Africa, and further highlights priority areas where efforts could be intensified in the next decade with potential to improve the current rate of progress toward achieving a 33% reduction in CVD mortality.

The development of Parkinson's disease is accompanied by concurrent activation of caspase-3 and apoptosis of dopaminergic neurons of human patients and rodent models. The role of caspase-3, a final executioner of apoptosis, in the pathogenesis of Parkinson's disease, however, remains to be determined. Here, we show that gene disruption of caspase-3 protects mice from 1-methyle-4-phenyl-1,2,3,6-tetrahmydropyridine (MPTP)-induced Parkinsonian syndrome, as reflected by reversal of MPTP-induced bradykinesia and decreased tyrosine hydroxylase expression in the nigra-striatum. MPTP treatment resulted in increased caspase-3 activation and apoptosis in the substantia nigra of wild-type mice at 24 h after the inception of MPTP treatment, as compared with vehicle-treated control animals. Gene disruption of caspase-3 prevented MPTP-induced apoptosis in the substantia nigra. At 7 days after MPTP treatment, tyrosine hydroxylase expression was suppressed and infiltration of activated microglia and astrocytes was markedly increased in the nigra-striatum of wild-type mice. All of these alterations following MPTP treatment were blocked by disruption of caspase-3 in mice. These results clearly indicate that caspase-3 activation is required for the development of MPTP-induced Parkinson's disease in mice. These findings suggest that activation of caspase-3-mediated apoptosis of dopaminergic neurons in the early stage may play an important role in the pathogenesis of Parkinson's disease.

Background Following reports of anti-retroviral therapy (ART) experienced Ugandan people living with HIV (PLHIV) presenting with diabetic ketoacidosis weeks to months following a switch to dolutegravir (DTG), the Uganda Ministry of Health recommended withholding DTG in both ART naïve and experienced PLHIV with diabetes mellitus (T2DM), as well as 3-monthly blood glucose monitoring for patients with T2DM risk factors. We sought to determine if the risk of T2DM is indeed heightened in nondiabetic ART naïve Ugandan PLHIV over the first 48 weeks on DTG. Methods Between January and October 2021, 243 PLHIV without T2DM were initiated on DTG based ART for 48 weeks. Two-hour oral glucose tolerance tests (2-h OGTT) were performed at baseline, 12, and 36 weeks; fasting blood glucose (FBG) was measured at 24 and 48 weeks. The primary outcome was the incidence of T2DM. Secondary outcomes included: incidence of pre-Diabetes Mellitus (pre-DM), median change in FBG from baseline to week 48 and 2-h blood glucose (2hBG) from baseline to week 36. Linear regression models were used to determine adjusted differences in FBG and 2hBG from baseline to weeks 48 and 36 respectively. Results The incidence of T2DM was 4 cases per 1000 PY (1/243) and pre-DM, 240 cases per 1000 person years (PY) (54/243). There was a significant increase in FBG from baseline to week 48 [median change from baseline (FBG): 3.6 mg/dl, interquartile range (IQR): − 3.6, 7.2, p-value (p) = 0.005] and significant reduction in 2hBG (2hBG: − 7.26 mg/dl, IQR: − 21.6, 14.4, p = 0.024) at week 36. A high CD4 count and increased waist circumference were associated with 2hBG increase at week 36. Conclusion We demonstrated a low incidence of T2DM in Ugandan ART-naïve patients receiving DTG. We also demonstrated that longitudinal changes in BG were independent of conventional risk factors of T2DM in the first 48 weeks of therapy. Restricting the use of dolutegravir in Ugandan ART naïve patients perceived to be high risk for diabetes mellitus may be unwarranted.

Background Cardiometabolic diseases are a leading cause of HIV-related morbidity and mortality, yet routine screening is not undertaken in high burden countries. We aimed to assess the prevalence and risk factors of the metabolic syndrome (MetS) and its components in adult Ugandan people living with HIV (PWH) initiating dolutegravir-based antiretroviral therapy (ART). Methods We conducted a cross-sectional study using baseline sociodemographic and clinical data of PWH aged ≥ 18 years enrolled in the GLUMED (Glucose metabolism changes in Ugandan HIV patients on Dolutegravir) Study from January to October 2021. MetS was defined as having ≥ 3 of the following: abdominal obesity, hypertension (HTN), hyperglycemia, elevated triglycerides and low high-density lipoprotein cholesterol. Multiple logistic regression was used to assess associations between potential risk factors and MetS and its components. Results 309 PWH were analyzed (100% ART-naive, 59.2% female, median age 31 years and median CD4 count 318 cells/mm3). The prevalence of MetS was 13.9%. The most common cardiometabolic condition was dyslipidemia (93.6%), followed by abdominal obesity (34.0%), hyperglycemia (18.4%), and HTN (8.1%). In adjusted analysis, MetS was associated with age > 40 years (adjusted odds ratio 3.33, 95% confidence interval 1.45-7.67) and CD4 count > 200 cells/mm3 (3.79, 1.23-11.63). HTN was associated with age > 40 years (2.96, 1.32-6.64), and dyslipidemia was associated with urban residence (4.99, 1.35-18.53). Conclusion Cardiometabolic risk factors were common in this young Ugandan cohort of PWH initiating dolutegravir-based ART, underscoring the need for programmatic implementation of surveillance and management of comorbidities in Uganda and similar settings.