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

Serum levels of lipoprotein(a) in HIV positive patients on HAART at Livingstone General Hospital, Livingstone, Southern Province, Zambia

Title: Serum levels of Lipoprotein(a) in HIV positive patients on HAART at Livingstone General Hospital, Livingstone, Southern Province, Zambia. Background: Lipoprotein(a) (Lp(a)) is a highly atherogenic independent risk marker for Cardiovascular disease (CVD) and current studies have shown that Highly Active Antiretroviral Therapy (HAART) raises Lp(a) levels in HIV patients, thereby increasing their risk for CVD. In this study, Lp(a) distribution in HIV patients on HAART were determined as well as their risk category for CVD based on their Lp(a) concentrations. Methods: This cross sectional laboratory based study was conducted between December 2014 to February 2015 at Livingstone General Hospital where fasting serum samples were collected and sent to the University Teaching Hospital Biochemistry laboratory for analysis. The Demographic and clinical data from patient files used were age, gender, ART combination and duration on ART. For data analysis, STATA version 12.0 and SPSS version 17.0 were used. The Study sample comprised of 57 (39.9%) males and 86 (60.1%) females who had been on ART from one to ten years. Results: Lp(a) concentration mean was 0.86 μmol/L ± 0.45μmol/L. Prevalence of high Lp(a) was 31.5% of which 29.4% and 2.1% were in the high risk and very high risk for CVD categories respectively. There was a significant relationship between age (p=0.009), duration on HAART (p<0.001) and high Lp(a) levels. Conclusion: Since Lp(a) tended to be raised with increasing age (p=0.009) and longer duration on HAART (p <0.001), this implies that age & duration on HAART were risk factors for CVD and contributed significantly to high prevalence levels of high Lp(a) in HIV patients on HAART

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]

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

The value of procalcitonin and C-reactive protein as early markers of bacteraemia among patients with haematological malignancies receiving chemotherapy: a cross-sectional study

This article evaluates the value of PCT and CRP, in early diagnosis of bacterial infections in patients with haematological malignancies on chemotherapy.The immune system of patients with haematological malignancies is suppressed during chemotherapy. This renders them vulnerable to frequent infections especially of the bacterial type. Timely diagnosis of these infections is difficult, because a severe infection may be asymptomatic or manifest only in the form of fever or malaise. There is need for laboratory markers that can detect an infectious process at an early stage. This study was aimed at determining the value of using Procalcitonin (PCT) and C reactive protein (CRP), for early diagnosis of infection in patients with haematological malignancies receiving chemotherapy. Methods: This was a cross sectional study consisting of sixty eight (68) patients with haematological malignancies. Data from each participant including sex, age, clinical and laboratory data were collected after obtaining informed consent. Blood specimens were then collected for measurement of PCT, CRP and bacteriological analysis. Patients were divided into two groups; those with a culture positive and negative result. PCT and CRP concentrations were compared between groups using t-test and nonparametric statistical tests respectively. The area under ROC curve, sensitivity, specificity, likelihood ratio, and Spearman's correlation coefficient were also calculated. Results: A total of 14 (20.6%) microorganisms were isolated, of which 10 were gram-positive bacteria and 4 were gram-negative bacilli. The mean values of PCT which were 6.1ng/mL in the bacteraemia group and 5.1ng/mL in the non-bacteraemia group, p=0.023 and median CRP values were 24.2 (6.4348.15) in the bacteraemia and 23.5 (6.03-75.44) in the non-bacteraemia group, p=0.832. The area under curves was 0.52 (95% CI=0.57-0.84) for CRP and 0.70 (95% CI=0.35-0.69) for PCT. PCT value of greater than 4.7 ng/mL is diagnostic for infections (sensitivity 86%, specificity 54%) while that of CRP was 21mg/mL with the sensitivity and specificity of 64% and 44% respectively. Elevated levels of PCT as well as fever were significantly associated with bacteraemia.Office of Global AIDS/US Department of State

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

Urine kidney injury molecule-1 predicts subclinical kidney disease among persons living with HIV initiating tenofovir disoproxil fumarate-based ART in Zambia

IntroductionAntiretroviral therapy (ART) increases the life expectancy of persons living with HIV (PLWH), but not without potentially serious adverse effects. Tenofovir disoproxil fumarate (TDF) can cause nephrotoxicity, manifesting as acute kidney injury (AKI) that may persist after treatment discontinuation. Kidney injury biomarkers such as kidney injury molecule-1 (KIM-1), retinol-binding protein-4 (RBP-4), interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) can aid early diagnosis and predict TDF-associated nephrotoxicity. This study aimed to determine whether the change from baseline in urine KIM-1 (δKIM-1) and NGAL (δNGAL) following 2 weeks of TDF use could predict subclinical TDF-associated nephrotoxicity before the overt manifestation as acute kidney disease after 3 months.MethodsA prospective cohort study of 205 PLWH was conducted at the Adult Center for Infectious Disease Research (AIDC) in Lusaka, Zambia. ART-naïve PLWH who were starting treatment with TDF with intact kidney function [estimated glomerular filtration rate (eGFR)&gt; 60 mL/min/1.73m2] were followed at initiation, 2 weeks, and approximately 3 months to determine the incidence of TDF-associated nephrotoxicity. We measured urine KIM-1 and NGAL at baseline and after 2 weeks of treatment to determine if it predicted subclinical nephrotoxicity. The presence of TDF-associated nephrotoxicity was defined according to the established acute kidney disease and disorders criteria (AKD) as having either 1) one or more episodes of eGFR&lt; 60ml/min/1.73m2 within 3 months, 2) a reduction in eGFR of greater than 35% (from baseline) within 3 months, and/or 3) an increase in serum creatinine of more than 50% (from baseline) within 3 months.ResultsThe incidence of TDF-associated nephrotoxicity was 22%. Baseline eGFR, creatinine, age, female sex, and BMI predicted the risk of overt TDF-associated nephrotoxicity. The median baseline KIM-1-to-creatinine and NGAL-1-to-creatinine ratios of the participants who developed overt TDF-associated nephrotoxicity and those who did not were not significantly different. However, every 1 pg/mg increase in δKIM-1 was associated with a 41% higher risk of TDF-associated nephrotoxicity. No association was observed with δNGAL.ConclusionsThe incidence of TDF-associated nephrotoxicity was high. Change in KIM-1 level within 2 weeks of the initiation of TDF treatment predicted subclinical TDF-associated nephrotoxicity before overt manifestation as acute kidney disease while δNGAL within the same period did not predict subclinical TDF-associated nephrotoxicity