Hypertensive heart disease: risk factors, complications and mechanisms

Hypertensive heart disease constitutes functional and structural dysfunction and pathogenesis occurring primarily in the left ventricle, the left atrium and the coronary arteries due to chronic uncontrolled hypertension. Hypertensive heart disease is underreported and the mechanisms underlying its correlates and complications are not well elaborated. In this review, we summarize the current understanding of hypertensive heart disease, we discuss in detail the mechanisms associated with development and complications of hypertensive heart disease especially left ventricular hypertrophy, atrial fibrillation, heart failure and coronary artery disease. We also briefly highlight the role of dietary salt, immunity and genetic predisposition in hypertensive heart disease pathogenesis

Gut microbiota dependant trimethylamine N-oxide and hypertension

The human gut microbiota environment is constantly changing and some specific changes influence the host’s metabolic, immune, and neuroendocrine functions. Emerging evidence of the gut microbiota’s role in the development of cardiovascular disease (CVD) including hypertension is remarkable. There is evidence showing that alterations in the gut microbiota and especially the gut-dependant metabolite trimethylamine N-oxide is associated with hypertension. However, there is a scarcity of literature addressing the role of trimethylamine N-oxide in hypertension pathogenesis. In this review, we discuss the impact of the gut microbiota and gut microbiota dependant trimethylamine N-oxide in the pathogenesis of hypertension. We present evidence from both human and animal studies and further discuss new insights relating to potential therapies for managing hypertension by altering the gut microbiota

The epithelial sodium channel in inflammation and blood pressure modulation

A major regulator of blood pressure and volume homeostasis in the kidney is the epithelial sodium channel (ENaC). ENaC is composed of alpha(α)/beta(β)/gamma(γ) or delta(δ)/beta(β)/gamma(γ) subunits. The δ subunit is functional in the guinea pig, but not in routinely used experimental rodent models including rat or mouse, and thus remains the least understood of the four subunits. While the δ subunit is poorly expressed in the human kidney, we recently found that its gene variants are associated with blood pressure and kidney function. The δ subunit is expressed in the human vasculature where it may influence vascular function. Moreover, we recently found that the δ subunit is also expressed human antigen presenting cells (APCs). Our studies indicate that extracellular Na+ enters APCs via ENaC leading to inflammation and salt-induced hypertension. In this review, we highlight recent findings on the role of extra-renal ENaC in inflammation, vascular dysfunction, and blood pressure modulation. Targeting extra-renal ENaC may provide new drug therapies for salt-induced hypertension

Immediate pressor response to oral salt and its assessment in the clinic: a time series clinical trial

Background: High blood pressure (BP) is associated with high-salt consumption especially in sub-Saharan Africa. Although the pressor efect of salt is viewed as a chronic efect, some studies suggest that a salty meal may increase BP immediately in some individuals, and that this efect may cause endothelial dysfunction. Therefore, the aim of our research was to study the immediate pressor response to oral salt (IPROS) and its determinants, with the expectation that a simple methodology may be devised to diagnose it in the clinic or in low-resource environments. Methods: We conducted a time series trial at Livingstone Central Hospital. We present data in 127 normotensive participants who ingested 2g of sodium chloride; their BP was monitored for 120minutes in intervals of 10minutes. Sociodemographic and clinical data were collected. Descriptive and inferential statistics were used for analyses of data. Results: Median age was 30 years (interquartile range, 22–46 years) and 52% were female patients. An increase of ≥10mmHg in mean arterial pressure (MAP), considered a clinically signifcant IPROS, was present in 62% of participants. Systolic BP 30minutes after the salt load was a signifcant predictor of IPROS, avoiding the need to calculate MAP in the clinic setting. Conclusions: We confrm the presence of an IPROS in a high proportion (62%) of otherwise normotensive participants. The average time course for this response was 30minutes and its duration was sustained for the 120-minutes period of study in most of the participants. Prediction of IPROS by ∆SBP (change in systolic blood pressure) at 30minutes allows for easy assessment of possible responder status in the clinic. Our data indicate that the IPROS to oral saltloads in the range currently consumed by the Western world and African populations in single meals may increase the 24-hour BP load, which is a risk factor for hypertension and target organ damage. The relevance of our fndings indicates the need to include dietary sodium assessment in the diagnosis, prevention, and management of high BP

HIV test-and-treat policy improves clinical outcomes in Zambian adults from Southern Province: a multicenter retrospective cohort study

BackgroundGlobally, most countries have implemented a test-and-treat policy to reduce morbidity and mortality associated with HIV infection. However, the impact of this strategy has not been critically appraised in many settings, including Zambia. We evaluated the retention and clinical outcomes of adults enrolled in antiretroviral therapy (ART) and assessed the impact of the test-and-treat policy.MethodsWe conducted a retrospective cohort study among 6,640 individuals who initiated ART between January 1, 2014 and July 31, 2016 [before test-and-treat cohort (BTT), n = 2,991] and between August 1, 2016 and October 1, 2020 [after test-and-treat cohort (ATT), n = 3,649] in 12 districts of the Southern province. To assess factors associated with retention, we used logistic regression (xtlogit model).ResultsThe median age [interquartile range (IQR)] was 34.8 years (28.0, 42.1), and 60.2% (n = 3,995) were women. The overall retention was 83.4% [95% confidence interval (CI) 82.6, 84.4], and it was significantly higher among the ATT cohort, 90.6 vs. 74.8%, p < 0.001. The reasons for attrition were higher in the BTT compared to the ATT cohorts: stopped treatment (0.3 vs. 0.1%), transferred out (9.3 vs. 3.2%), lost to follow-up (13.5 vs. 5.9%), and death (1.4 vs. 0.2%). Retention in care was significantly associated with the ATT cohort, increasing age and baseline body mass index (BMI), rural residence, and WHO stage 2, while non-retention was associated with never being married, divorced, and being in WHO stage 3.ConclusionThe retention rate and attrition factors improved in the ATT compared to the BTT cohorts. Drivers of retention were test-and-treat policy, older age, high BMI, rural residence, marital status, and WHO stage 1. Therefore, there is need for interventions targeting young people, urban residents, non-married people, and those in the symptomatic WHO stages and with low BMI. Our findings highlight improved ART retention after the implementation of the test-and-treat policy

Salt Taste and Salt Sensitive Hypertension in HIV

Purpose of Review: To provide a summary of current literature and propose potential mechanistic models to help us understand the role of HIV infection/antiretroviral therapy (ART), salt taste sensitivity (STS), and salt sensitivity of blood pressure (SSBP) in hypertension development. Recent Findings: The epithelial sodium channel (ENaC) is the main protein/sodium channel for recognizing Na + in the tongue and mediates preference to low-medium salt concentrations in animals and humans. Considering the pressor response to oral salt in individuals with SSBP, poor STS may worsen blood pressure. Specific genetic variants in ENaC are linked to salt taste perception and hypertension. HIV infection, some ART, and specific antihypertensive drugs are associated with reduced STS and an increased liking for salty foods. Summary: Persons with HIV (PWH) on ART may have a decreased STS and are at a higher risk of developing saltsensitive hypertension. Inflammation mediated by dietary salt is one of the drivers of poor STS and saltsensitive hypertension among PWH

Rifampicin resistance in mycobacterium tuberculosis patients using GeneXpert at Livingstone Central Hospital for the year 2015: a cross sectional explorative study

Abstract Background Since the recent introduction of GeneXepert for the detection of Tuberculosis (TB) drug resistance mutations in both primary resistance and acquired resistance in Zambia, little has been documented in literature on the issue of rifampicin resistance especially in the face of a high National TB burden. The study aimed to determine the prevalence of rifampicin resistance in tuberculosis patients at Livingstone Central Hospital for the year 2015. Methods This was a cross sectional study conducted at Livingstone Central Hospital where we reviewed 152 records (from January 1, 2015 to 31st December, 2015) involving patients who presented with clinically suspected TB or documented TB, whose samples were sent to the laboratory for GeneXpert Mycobacterium tuberculosis/rifampicin testing. Statistical evaluations used a one-sample test of proportion and Fisher’s exact test. Results The age of participants ranged from 8 months to 73 years old (median = 34). Of the participants with complete data on gender, 99 (66%) and 52 (34%) were males and females respectively. The TB co-infection with HIV prevalence was 98.3% (p < 0.001). Prevalence of rifampicin resistance was 5.9% and there was no statistical significant difference between being male or female (p = 0.721). Conclusion We were able to show from our study, evidence of rifampicin resistance at Livingstone Central Hospital. Hence, there was need for further in-depth research and appropriate interventions (i.e close follow-up and patient care for drug resistance positive patients)

Erythrocyte sodium buffering capacity status correlates with self-reported salt intake in a population from Livingstone, Zambia

Background Salt impairs endothelial function and increases arterial stiffness independent of blood pressure. The mechanisms are unknown. Recent evidence suggests that there is a possible link between salt consumption and sodium buffering capacity and cardiovascular disease but there is limited evidence in the populations living in Sub-Saharan Africa. The aim of our study was to explore the relationship between erythrocyte sodium buffering capacity and sociodemographic, clinical factors, and self-reported salt consumption at Livingstone Central Hospital. Methods We conducted a cross sectional study at Livingstone Central hospital among 242 volunteers accessing routine medical checkups. Sociodemographic and dietary characteristics were obtained along with clinical measurements to evaluate their health status. Sodium buffering capacity was estimated by erythrocyte sodium sensitivity (ESS) test. We used descriptive and inferential statistics to describe and examine associations between erythrocyte sodium sensitivity and independent variables. Results The median age (interquartile range) of the study sample was 27 (22, 42) years. 54% (n=202) and 46% (n=169) were males and females, respectively. The majority (n=150, 62%) had an ESS of >120%. High salt intake correlated positively with ESS or negatively with vascular sodium buffering capacity. Conclusions Self-reported high salt intake was associated with poor vascular sodium buffering capacity or high ESS in the majority of middle-aged Zambians living in Livingstone. The poor vascular sodium buffering capacity implies a damaged vascular glycocalyx which may potentially lead to a leakage of sodium into the interstitium. This alone is a risk factor for the future development of hypertension and cardiovascular disease. However, future studies need to validate vascular function status when using ESS testing by including established vascular function assessments to determine its pathophysiological and clinical implications. Keywords: Erythrocyte sodium sensitivity, sodium buffering capacity, vascular health, salt, red blood cell

Mechanisms of Oxidative Stress in Metabolic Syndrome

Metabolic syndrome is a cluster of conditions associated with the risk of diabetes mellitus type 2 and cardiovascular diseases (CVDs). Metabolic syndrome is closely related to obesity. Increased adiposity promotes inflammation and oxidative stress, which are precursors of various complications involving metabolic syndrome components, namely insulin resistance, hypertension, and hyperlipidemia. An increasing number of studies confirm the importance of oxidative stress and chronic inflammation in the etiology of metabolic syndrome. However, few studies have reviewed the mechanisms underlying the role of oxidative stress in contributing to metabolic syndrome. In this review, we highlight mechanisms by which reactive oxygen species (ROS) increase mitochondrial dysfunction, protein damage, lipid peroxidation, and impair antioxidant function in metabolic syndrome. Biomarkers of oxidative stress can be used in disease diagnosis and evaluation of severity

Productivity-adjusted life-years and correlates of uncontrolled hypertension at two health facilities in Zambia.

BackgroundHypertension has in the recent past surfaced as one of the conditions that has a significant impact on workforce productivity in emerging economies. Zambia is no different and has in the recent past recorded increasing cases. Despite the impact of hypertension being of great importance in regards to productivity, we have scarcity of data and studies on hypertension-related Productivity-Adjusted Life-Years (PALYs) in Zambia and Africa at large. This study assessed the impact of hypertension on PALYs lost and socioeconomic factors associated with nonadherence to antihypertensive medication (NATAM).MethodsThis was a cross-sectional study of 198 participants from Livingstone University Teaching Hospital and Maramba Clinic situated in Livingstone, Zambia. Structured questionnaires were used to collect data. Productivity index multiplied by years lived was used to calculate PALYs and descriptive statistics were used to summarize sociodemographic, clinical and economic variables. Multivariable logistic regression was used to determine factors associated with NATAM.ResultsThe participants had a median age (interquartile range (IQR)) of 49 years (41, 59) and 60.1% (n = 119) were females while 39.9% (n = 79) were male. Our estimated PALYs lost per person due to hypertension were 0.2 (IQR 0.0, 2.7). Cumulative PALYs value lost due to the burden of hypertension was estimated to be at $871,239.58 in gross domestic product (GDP). The prevalence of NATAM was 48% (n = 95). The factors that were significantly associated with NATAM were age (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.90, 0.98), female sex (OR 2.52; 95%CI 1.18, 5.40), self-employment (OR 2.57; 95%CI 1.02, 6.45) and absenteeism from work (OR 3.60; 95%CI 1.16, 11.22).ConclusionsFindings in our study highlight a high economic loss of PALYs due to hypertension with a potential to impact GDP negatively. We also found that NATAM reduced productivity and income among individuals of working age further impacting PALYs lost due to hypertension. The factors associated with NATAM were age, sex, employment status and absenteeism from work. This study underscores the need for interventions targeting young people, females, self-employed individuals, and absentees at work to improve adherence to antihypertensive drugs in order to reduce PALYs lost due to hypertension