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

Erythrocyte glycocalyx sensitivity to sodium is associated with salt sensitivity of blood pressure in women but not men

BackgroundWhile salt sensitivity of blood pressure (SSBP) is a risk factor for hypertension, end-organ damage and death, most studies are conducted in western countries and in White people. We previously found that the prevalence of SSBP in Blacks living in Sub-Saharan Africa is as high as 75–80% like what has been reported in the west. Erythrocyte glycocalyx sensitivity to sodium (eGCSS), a marker of sodium-induced damage to the erythrocyte and vascular endothelial glycocalyx is thought to be related to blood pressure perturbations associated with salt intake. We hypothesized that SSBP correlates with eGCSS differently in men and women in Black people.MethodsWe conducted a cross sectional study using data from our recent clinical trial from Livingstone University Teaching Hospital among 117 normotensive young adults. We used a “salt blood test” to determine eGCSS and an immediate pressor response to oral salt (IPROS) for the diagnosis of SSBP.ResultsThe proportion of males were equal to females and the median age (interquartile range) of the participants was 29 (22–45) years. The eGCSS scores were higher in salt-resistant females compared to salt-sensitive females and males. eGCSS correlated negatively with SSBP (AOR 0.98, 95% CI 0.97–0.99, p = 0.008), however, this relationship was driven by female sex and abrogated by male sex. Although blood pressure elevations exhibited a sustained bimodal pattern in both sexes, in males, systolic and diastolic blood pressure never returned to baseline during the time course as it did in females.ConclusionIn this study, eGCSS correlated negatively with SSBP in black women but not in black men and the pressor response to dietary salt was significantly higher in men compared to women. These results suggest that women tend to have a higher disruption of the vascular endothelial glycocalyx by an acute salt load, implying that acute changes in blood pressure may not be driven directly by the endothelial glycocalyx. Our findings suggest a novel mechanism linking eGCSS and SSBP with potential implications for sex differences in salt-induced cardiovascular disease.Clinical trial registration: https://clinicaltrials.gov/, identifier [NCT04844255]

Cervical cancer and precancerous cervical lesions detected using visual inspection with acetic acid at Livingstone Teaching Hospital

Introduction: cervical cancer (CaCx) is the second most common malignancy in women world-wide. Precancer screening aided by visual inspection with acetic acid (VIA) is an early diagnosis method used to detect the lesions that are high indicators of cancer in women. cervical cancer is more prevalent in the developing world affecting mainly women in the reproductive age group and is the commonest cancer among Zambian women. Therefore, the study aimed to determine the prevalence and factors associated with a positive VIA at Livingstone Teaching Hospital (LTH). Methods: this was a cross-sectional study conducted at LTH among 329 women from Livingstone district aged 18 and above, who were coming for routine cervical cancer screening using VIA between 2019 and 2020. Demographic and clinical data were collected from the CaCx clinic. A positive VIA (precancerous cervical lesions) and cervical cancer were the primary and secondary outcome variables. A positive VIA was defined by presence of a dense ulcerative acetowhite area in the transformation zone of the cervix. Cervical cancer diagnosis was defined by presence of cancerous cells on histological examination by a qualified pathologist. Data were analyzed using Statistical package for social sciences (SPSS) version 22.0. Chi-square test, Mann-Whitney and logistic regression were the statistical methods used. Results: the participants had a median (interquartile range) age of 37 (29, 44) years. Prevalence of CaCx and positive VIA were 6% (95% confidence interval (CI) 4, 9) and 19% (95% CI: 15, 24) respectively. At multivariable analysis, the factors associated with a positive VIA were alcohol consumption [odds ratio (OR) 0.30 (95% CI: 0.12, 0.74)] and HIV infection [OR 0.37 (95% CI: 0.19, 0.70)]. Conclusion: the study showed that precancerous cervical lesions are common among our study participants and it was influenced by alcohol consumption and HIV status. There is therefore need to enhance the screening programs using VIA in order to identify cancerous lesions at an early stage for early intervention in resource limited settings

HIV-positive demonstrate more salt sensitivity and nocturnal non-dipping blood pressure than HIV-negative individuals

Background: High dietary salt and a lack of reduced blood pressure (BP) at night (non-dipping) are risk factors for the development of hypertension which may result in end-organ damage and death. The effect of high dietary salt on BP in black people of sub-Saharan Africa living with HIV is not well established. The goal of this study was to explore the associations between salt sensitivity and nocturnal blood pressure dipping according to HIV and hypertension status in a cohort of adult Zambian population. Methods: We conducted an interventional study among 43 HIV-positive and 42 HIV-negative adults matched for age and sex. Study participants were instructed to consume a low (4 g) dietary salt intake for a week followed by high (9 g) dietary salt intake for a week. Salt resistance and salt sensitivity were defined by a mean arterial pressure difference of ≤5 mmHg and ≥ 8 mmHg, respectively, between the last day of low and high dietary salt intervention. Nocturnal dipping was defined as a 10–15% decrease in night-time blood pressure measured with an ambulatory blood pressure monitor. Results: The median age was 40 years for both the HIV-positive and the HIV-negative group with 1:1 male to female ratio. HIV positive individuals with hypertension exhibited a higher BP sensitivity to salt (95%) and nondipping BP (86%) prevalence compared with the HIV negative hypertensive (71 and 67%), HIV positive (10 and 24%) and HIV-negative normotensive (29 and 52%) groups, respectively (p < 0.05). Salt sensitivity was associated with non-dipping BP and hypertension in both the HIV-positive and HIV-negative groups even after adjustment in multivariate logistic regression (< 0.001). Conclusions: The results of the present study suggest that high dietary salt intake raises blood pressure and worsens nocturnal BP dipping to a greater extent in hypertensive than normotensive individuals and that hypertensive individuals have higher dietary salt intake than their normotensive counterparts. Regarding HIV status, BP of HIV-positive hypertensive patients may be more sensitive to salt intake and demonstrate more non-dipping pattern compared to HIV-negative hypertensive group. However, further studies with a larger sample size are required to validate this

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 &lt; 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

Predictors of diarrhea episodes and treatment-seeking behavior in under-five children: a longitudinal study from rural communities in Zambia

Introduction:&nbsp;globally, diarrhea is the second leading cause of mortality in children aged below five years, and is responsible for killing about 760 000 children every year. Poor treatment-seeking behavior among caretakers remains a major challenge in low-income countries. The current study aimed to determine the predictors of diarrhea episodes and treatment-seeking behavior among under-five children of Chivuna and Magoye in Zambia. Methods:&nbsp;we conducted a community-based longitudinal study among 1216 children aged 12-59 months between July 2006 and June 2007. A structured interviewer-administered questionnaire was used to collect data on demographic factors, diarrhea episodes and treatment-seeking behavior from caretakers. Chi-square, one-sample test of proportions and logistic regression were the statistical methods used in this study. Results:&nbsp;of the 1216 children who participated in the study, 698 (57%) were from Chivuna and 518 (43%) from Magoye. Factors associated with diarrhea episodes were location (children in Chivuna had increased episodes of diarrhea; aOR 1.32; 95%CI 1.15, 1.52) and age distribution (children aged 37-59 months vs. 12-36 months had reduced episodes of diarrheal aOR 0.81; 95%CI 0.72, 0.91). Fifty two percent (52%) of the diarrhea cases had their treatment sought within 24 hours of onset (early treatment). Thirty one percent (31%) of the diarrhea cases had their early treatment at a health facility. Female children (52%) had the majority of their diarrhea episodes treated within 24 hours of onset. The higher proportion of diarrhea episodes had their treatment at home (52%). Children who did not have home treatment had a significantly reduced chance of having early treatment (aOR 0.62; 95%CI 0.47, 0.82). Conclusion:&nbsp;this study revealed that diarrhea episodes and treatment seeking behavior in under-5 children is of public health concern. There is need to re-enforce the preventative and control measures aimed at reducing diarrhea in under-5 children, and interventions should take into account the different predictors of diarrhea and treatment seeking behavior in different settings, like the ones highlighted in this study