Salt Sensitivity of Blood Pressure.

The year 2024 marks the centennial of the initiation of the American Heart Association. Over the past 100 years, the American Heart Association has led groundbreaking discoveries in cardiovascular disease including salt sensitivity of blood pressure, which has been studied since the mid-1900s. Salt sensitivity of blood pressure is an important risk factor for cardiovascular events, but the phenotype remains unclear because of insufficient understanding of the underlying mechanisms and lack of feasible diagnostic tools. In honor of this centennial, we commemorate the initial discovery of salt sensitivity of blood pressure and chronicle the subsequent scientific discoveries and efforts to mitigate salt-induced cardiovascular disease with American Heart Association leading the way. We also highlight determinants of the pathophysiology of salt sensitivity of blood pressure in humans and recent developments in diagnostic methods and future prospects.

HIV-Associated Hypertension: Risks, Mechanisms, and Knowledge Gaps.

HIV type 1 (HIV-1) is the causative agent of AIDS. Since the start of the epidemic, HIV/AIDS has been responsible for ≈40 million deaths. Additionally, an estimated 39 million people are currently infected with the virus. HIV-1 primarily infects immune cells, such as CD4+ (cluster of differentiation 4+) T lymphocytes (T cells), and as a consequence, the number of CD4+ T cells progressively declines in people living with HIV. Within a span of ≈10 years, HIV-1 infection leads to the systemic failure of the immune system and progression to AIDS. Fortunately, potent antiviral therapy effectively controls HIV-1 infection and prevents AIDS-related deaths. The efficacy of the current antiviral therapy regimens has transformed the outcome of HIV/AIDS from a death sentence to a chronic disease with a prolonged lifespan of people living with HIV. However, antiviral therapy is not curative, is challenged by virus resistance, can be toxic, and, most importantly, requires lifelong adherence. Furthermore, the improved lifespan has resulted in an increased incidence of non-AIDS-related morbidities in people living with HIV including cardiovascular diseases, renal disease, liver disease, bone disease, cancer, and neurological conditions. In this review, we summarize the current state of knowledge of the cardiovascular comorbidities associated with HIV-1 infection, with a particular focus on hypertension. We also discuss the potential mechanisms known to drive HIV-1-associated hypertension and the knowledge gaps in our understanding of this comorbid condition. Finally, we suggest several directions of future research to better understand the factors, pathways, and mechanisms underlying HIV-1-associated hypertension in the post-antiviral therapy era.

The Interplay of HIV and Long COVID in Sub-Saharan Africa: Mechanisms of Endothelial Dysfunction.

PURPOSE OF REVIEW: Long COVID affects approximately 5 million people in Africa. This disease is characterized by persistent symptoms or new onset of symptoms after an acute SARS-CoV-2 infection. Specifically, the most common symptoms include a range of cardiovascular problems such as chest pain, orthostatic intolerance, tachycardia, syncope, and uncontrolled hypertension. Importantly, these conditions appear to have endothelial dysfunction as the common denominator, which is often due to impaired nitric oxide (NO) mechanisms. This review discusses the role of mechanisms contributing to endothelial dysfunction in Long COVID, particularly in people living with HIV. RECENT FINDINGS: Recent studies have reported that increased inflammation and oxidative stress, frequently observed in Long COVID, may contribute to NO dysfunction, ultimately leading to decreased vascular reactivity. These mechanisms have also been reported in people living with HIV. In regions like Africa, where HIV infection is still a major public health challenge with a prevalence of approximately 26 million people in 2022. Specifically, endothelial dysfunction has been reported as a major mechanism that appears to contribute to cardiovascular diseases and the intersection with Long COVID mechanisms is of particular concern. Further, it is well established that this population is more likely to develop Long COVID following infection with SARS-CoV-2. Therefore, concomitant infection with SARS-CoV-2 may lead to accelerated cardiovascular disease. We outline the details of the worsening health problems caused by Long COVID, which exacerbate pre-existing conditions such as endothelial dysfunction. The overlapping mechanisms of HIV and SARS-CoV-2, particularly the prolonged inflammatory response and chronic hypoxia, may increase susceptibility to Long COVID. Addressing these overlapping health issues is critical as it provides clinical entry points for interventions that could improve and enhance outcomes and quality of life for those affected by both HIV and Long COVID in the region.

Salt and Gut Microbiota in Heart Failure.

PURPOSE OF REVIEW: The role and underlying mechanisms mediated by dietary salt in modulating the gut microbiota and contributing to heart failure (HF) are not clear. This review summarizes the mechanisms of dietary salt and the gut-heart axis in HF. RECENT FINDINGS: The gut microbiota has been implicated in several cardiovascular diseases (CVDs) including HF. Dietary factors including high consumption of salt play a role in influencing the gut microbiota, resulting in dysbiosis. An imbalance of microbial species due to a reduction in microbial diversity with accompanying immune cell activation has been implicated in the pathogenesis of HF via several mechanisms. The gut microbiota and gut-associated metabolites contribute to HF by reducing gut microbiota biodiversity and activating several signaling pathways. High dietary salt modulates the gut microbiota composition and exacerbate or induce HF by increasing the expression of the epithelial sodium/hydrogen exchanger isoform 3 in the gut, cardiac expression of beta myosin heavy chain, activation of the myocyte enhancer factor/nuclear factor of activated T cell, and salt-inducible kinase 1. These mechanisms explain the resulting structural and functional derangements in patients with HF.

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. Persons with HIV (PWH) on ART may have a decreased STS and are at a higher risk of developing salt-sensitive hypertension. Inflammation mediated by dietary salt is one of the drivers of poor STS and salt-sensitive hypertension among PWH.

Reach and uptake of mass drug administration for worm infections through health facility-, school-, and community-based approaches in two districts of Zambia: a call for scale-up.

Helminthiases cause significant health deficiencies among children. Mass administration of anthelminthic drugs has had significant results to counter these effects. We assessed the effects on and determinants of treatment coverage of community-directed treatment among children in Zambia, using cross-sectional survey data, and using chi-square test and multilevel mixed-effects model. Of 1,416 children, 51.5% were males and 48.5% were females, while 52.7%, were school-age, and 47.3% were preschool-age. Overall treatment coverage was 53.7% (95% confidence interval (CI) 51.1, 56.4). More preschool-age children were treated compared to school-age ones, 65.2% versus 43.4%, P < 0.001. Similarly, more children under community-directed intervention were treated compared to regular mass drug administration (65.2% versus 51.1 %, P < 0.001). Treatment among school-age participants was associated with being male (Adjusted Odds Ratio (AOR 1.83, 95%CI 1.23-2.72), receiving community-directed treatment (AOR 5.53; 95%CI 3.41-8.97), and shorter distance to health facility (AOR 2.20; 95%CI 1.36-3.56). Among preschool-aged participants, treatment was associated with being residents of Siavonga district (AOR 0.03; 95%CI 0.01-0.04) and shorter distance to health facility (AOR 0.35; 95%CI 0.21-0.59). Community-directed treatment can be used to increase treatment coverage, thereby contribute to 2030 vision of ending epidemics of neglected tropical diseases.

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.

Sox6, A Potential Target for MicroRNAs in Cardiometabolic Disease.

PURPOSE OF REVIEW: The study aims to review recent advances in knowledge on the interplay between miRNAs and the sex-determining Region Y (SRY)-related high-mobility-group box 6 (Sox6) in physiology and pathophysiology, highlighting an important role in autoimmune and cardiometabolic conditions. RECENT FINDINGS: The transcription factor Sox6 is an important member of the SoxD family and plays an indispensable role in adult tissue homeostasis, regeneration, and physiology. Abnormal expression of the Sox6 gene has been implicated in several disease conditions including diabetes, cardiomyopathy, autoimmune diseases, and hypertension. Expression of Sox6 is regulated by miRNAs, which are RNAs of about 22 nucleotides, and have also been implicated in several pathophysiological conditions where Sox6 plays a role. Regulation of Sox6 by miRNAs is important in diverse physiological tissues and organs. Dysregulation of the interplay between miRNAs and Sox6 is an important determinant of various disease conditions and may be actionable for therapeutic purposes.

Hypertension and Metabolic Syndrome in Persons with HIV.

PURPOSE OF REVIEW: With the advent of highly active antiretroviral therapy (ART), the life span of persons with HIV (PWH) has been nearly normalized. With aging, prevalence of the metabolic syndrome (MetS), including hypertension, has increased in the HIV population and exceeds that in the general population in some studies. This is due to a combination of traditional risk factors in addition to the effects attributable to the virus and ART. We review recent findings on the mechanisms contributing to MetS and hypertension in PWH, particularly those specific to the viral infection and to ART. RECENT FINDINGS: Activation of the renin-angiotensin-aldosterone system (RAAS) and chronic immune activation contribute to the development of MetS and hypertension in PWH. HIV proteins and some ART agents alter adipocyte health contributing to dyslipidemias, weight gain, and insulin resistance. HIV infection also contributes to hypertension by direct effects on the RAAS that intertwine with inflammation by the RAAS also contributing to T cell activation. Recent data suggest that in addition to current ART, therapeutic targeting of the MetS and hypertension in PWH, by interfering with the RAAS, treating insulin resistance directly or by use of immunomodulators that dampen inflammation, may be critical for preventing or treating these risk factors and to improve overall cardiovascular complications in the HIV-infected aging population.

Patho-immune Mechanisms of Hypertension in HIV: a Systematic and Thematic Review.

PURPOSE OF REVIEW: To systematically review recent findings on the role of immune cell activation in the pathogenesis of hypertension in people living with HIV (PLWH) and compare studies from Sub-Saharan Africa with what is reported in the USA and European literature according to guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RECENT FINDINGS: PLWH have an increased risk for development of hypertension and cardiovascular disease. Chronic immune activation contributes to hypertension but the inflammatory milieu that predisposes PLWH to hypertension is poorly understood. We identified 45 relevant studies from 13 unique African countries. The prevalence of hypertension in PLWH on antiretroviral therapy (ART) and the ART-naive PLWH ranged from 6 to 50% and 2 to 41%, respectively. Interleukin (IL)-17A, interferon (IFN)-γ, and higher CD4+ T cell counts were associated with hypertension in ART-treated participants. Targeting adaptive immune activation could provide improved care for hypertensive PLWH. Further research is needed to characterize the inflammatory milieu contributing to hypertension in PLWH especially in African populations where the global burden of HIV is the highest.

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

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).

High salt intake and HIV infection on endothelial glycocalyx shedding in salt-sensitive hypertension.

The endothelial glycocalyx is closely associated with various physiological and pathophysiological events. Significant modification of the endothelial glycocalyx is an early process in the pathogenesis of cardiovascular disease. High dietary salt and HIV infection damages the endothelial glycocalyx causing endothelial dysfunction and increasing the risk for salt-sensitive hypertension and cardiovascular disease. The two factors, HIV infection and dietary salt are critical independent predictors of hypertension and cardiovascular disease and often synergize to exacerbate and accelerate disease pathogenesis. Salt-sensitive hypertension is more common among people living with HIV and is associated with risk for cardiovascular disease, stroke, heart attack and even death. However, the underlying mechanisms linking endothelial glycocalyx damage to dietary salt and HIV infection are lacking. Yet, both HIV infection/treatment and dietary salt are closely linked to endothelial glycocalyx damage and development of salt-sensitive hypertension. Moreover, the majority of individuals globally, consume more salt than is recommended and the burden of HIV especially in sub-Sahara Africa is disproportionately high. In this review, we have discussed the missing link between high salt and endothelial glycocalyx shedding in the pathogenesis of salt-sensitive hypertension. We have further elaborated the role played by HIV infection and treatment in modifying endothelial glycocalyx integrity to contribute to the development of hypertension and cardiovascular disease.

Mechanisms and Cardiorenal Complications of Chronic Anemia in People with HIV.

Chronic anemia is more prevalent in people living with HIV (PLWH) compared to the general population. The mechanisms that drive chronic anemia in HIV are multifaceted and include functional impairment of hematopoietic stem cells, dysregulation of erythropoietin production, and persistent immune activation. Chronic inflammation from HIV infection adversely affects erythropoiesis, erythrocyte lifespan, and erythropoietin response, leading to a heightened risk of co-infections such as tuberculosis, persistent severe anemia, and increased mortality. Additionally, chronic anemia exacerbates the progression of HIV-associated nephrotoxicity and contributes to cardiovascular risk through immune activation and inflammation. This review highlights the cardinal role of chronic inflammation as a link connecting persistent anemia and cardiovascular complications in PLWH, emphasizing the need for a universal understanding of these interconnected pathways for targeted interventions.

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

Background: While 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. Methods: We 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. Results: The 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. Conclusion: In 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].

Viral load suppression and HIV-1 drug resistance mutations in persons with HIV on TLD/TAFED in Zambia.

BACKGROUND: An increase in the prevalence of HIV drug resistance (HIVDR) has been reported in recent years, especially in persons on non-nucleoside reverse transcriptase inhibitors (NNRTIs) due to their low genetic barrier to mutations. However, there is a paucity of epidemiological data quantifying HIVDR in the era of new drugs like dolutegravir (DTG) in sub-Saharan Africa. We, therefore, sought to determine the prevalence and correlates of viral load (VL) suppression in adult people with HIV (PWH) on a fixed-dose combination of tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) or tenofovir alafenamide/emtricitabine/dolutegravir (TAFED) and describe patterns of mutations in individuals failing treatment. METHODS: We conducted a cross-sectional study among 384 adults living with HIV aged ≥15 years between 5th June 2023 and 10th August 2023. Demographic, laboratory and clinical data were collected from electronic health records using a data collection form. Viral load suppression was defined as plasma HIV-1 RNA VL of <1000 copies/ml after being on ART for ≥ 6 months. SPSS version 22 to analyze the data. Descriptive statistics and logistic regression were the statistical methods used. RESULTS: The median (interquartile range (IQR)) age was 22 (IQR 18, 38) years, and 66.1% (n = 254) were females. VL suppression was 90.4% (n = 347); (95% confidence interval (CI) 87.6%-93.6%) after switching to TLD/TAFED. Among the virally suppressed, the majority (67.1%, n = 233) were female. Those who missed ≥2 doses in the last 30 days prior to the most recent review were less likely to attain viral suppression compared to those who did not miss any dose (adjusted odds ratio (AOR) 0.047; 95% CI 0.016-0.136; p<0.001). Four participants had resistance mutations to lamivudine and tenofovir. The most common NRTI mutations were M184MV and K65R while K101E was the most common NNRTI mutation. CONCLUSION: Our findings show that viral suppression was high after switching to TLD/TAFED; but lower than the last 95% target of the UNAIDS. Adherence to antiretroviral therapy was a significant correlate of VL suppression. We, therefore, recommend prompt switching of PWH to TLD/TAFED regimen and close monitoring to enhance adherence to therapy.

Severe acute malnutrition among children under the age of 5 years.

BACKGROUND: Severe acute malnutrition (SAM) poses a significant threat to child health globally, particularly in low- and middle-income countries. Zambia, like many Sub-Saharan African nations, faces high rates of child malnutrition, with SAM contributing significantly to under-five mortality. Therefore, this study aimed to determine the prevalence and factors associated with SAM. METHODS: This retrospective cross-sectional study was conducted at Livingstone University Teaching Hospital in Zambia (LUTH). SAM was defined according to the World Health Organization (WHO) criteria as either weight-for-height less than -3 standard deviations, mid-upper arm circumference (MUAC) less than 115 mm, or presence of bilateral pitting edema in children between 6 months and 5 years old who were attended to between 2020 and 2022. Data abstraction from pediatric patient records was conducted between August 2023 and January 2024. The records without the age and outcome variable were excluded. A total of 429 participants between 6 months and 5 years old were included, with demographic, clinical, and hematological parameters analyzed. Univariable and multivariable logistic regression were employed to investigate factors associated with SAM. RESULTS: Overall, 429 medical records were included in the study and the prevalence of SAM was 27.0% (n = 116). Age group 6-24 months (Adjusted Odds Ratio [AOR]: 11.60; 95% Confidence Interval [CI]: 3.34-40.89, p<0.001), living with HIV (AOR:3.90; 95% CI: 1.14-13.70, p = 0.034), Tuberculosis (TB) (AOR:22.30, 95% CI: 4.53, 110.3, p < 0.001), comorbidities (AOR: 2.50; 95% CI 1.13, 5.88, p = 0.024) and platelet count (AOR: 1.00; 95% CI 1.00, 1.00, p = 0.027) were positively associated with SAM. CONCLUSIONS: This study found a high prevalence of SAM, exceeding the WHO target of reducing SAM to 5% by 2025. SAM was associated with younger age (6-24 months), HIV infection, TB, comorbidities and platelet count. Therefore, there is need to enhance strategies aimed at reducing SAM among young children, children living with HIV, TB and comorbidities, particularly by intensive treatment, continuing and strengthening nutrition services.

Prevalence and correlates of Human Papillomavirus infection in females from Southern Province, Zambia: A cross-sectional study.

BACKGROUND: Human papillomavirus (HPV) infection is strongly associated with cervical cancer with almost all cases being associated with the infection. Cervical cancer is the leading cause of cancer death among women in Zambia and the fourth leading cause of cancer death in women worldwide. However, there is limited data on the burden and associated factors of HPV in sub-Saharan Africa. This study therefore aimed to determine the prevalence and correlates of HPV infection in the Southern province of Zambia. METHODS: This was a cross-sectional study conducted at Livingstone University Teaching Hospital (LUTH) among 4,612 women from different districts of the southern province being screened for HPV infection between September 2021 and August 2022. Demographic and clinical data were collected from an existing laboratory programmatic database. Multivariable logistic regression was used to estimate the factors associated with HPV infection. RESULTS: The study participants had a median age of 39 years [interquartile range (IQR) 30, 47]. The prevalence of HPV infection was 35.56% (95%CI). At multivariable analysis, the factors associated with a positive HPV result were younger age (adjusted odds ratio (AOR) 0.98; 95% confidence interval (CI) 0.98-0.99; p. value 0.001), having provider collected sample (AOR 2.15; 95%CI 1.66-2.79; p. value <0.001) and living with HIV (AOR 1.77; 95%CI 1.22-2.55; p. value <0.002). CONCLUSION: The prevalence of HPV in women in the southern province of Zambia is high, and likely influenced by age and HIV status. Additionally, the outcome of the HPV test is affected by the sample collection method. Therefore, there is a necessity to enhance HPV and cervical cancer screening, especially among people with HIV.

Recent Advances in Understanding Peripheral and Gut Immune Cell-Mediated Salt-Sensitive Hypertension and Nephropathy.

Hypertension is the primary modifiable risk factor for cardiovascular, renal, and cerebrovascular diseases and is considered the main contributing factor to morbidity and mortality worldwide. Approximately 50% of hypertensive and 25% of normotensive people exhibit salt sensitivity of blood pressure, which is an independent risk factor for cardiovascular disease. Human and animal studies demonstrate that the immune system plays an important role in the etiology and pathogenesis of salt sensitivity of blood pressure, kidney damage, and vascular diseases. Antigen-presenting and adaptive immune cells are implicated in salt-sensitive hypertension and salt-induced renal and vascular injury. Elevated sodium activates antigen-presenting cells to release proinflammatory cytokines including IL (interleukin) 6, tumor necrosis factor-α, IL-1ß, and accumulate isolevuglandin-protein adducts. In turn, these activate T cells release prohypertensive cytokines including IL-17A. Moreover, high-salt intake is associated with gut dysbiosis, leading to inflammation, oxidative stress, and blood pressure elevation but the mechanistic contribution to salt-sensitivity of blood pressure is not clearly understood. Here, we discuss recent advances in research investigating the cause, potential biomarkers, and therapeutic targets for salt-sensitive hypertension as they pertain to the gut microbiome, immunity, and inflammation.

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.

Recent Advances in Microbiota-Associated Metabolites in Heart Failure.

Heart failure is a risk factor for adverse events such as sudden cardiac arrest, liver and kidney failure and death. The gut microbiota and its metabolites are directly linked to the pathogenesis of heart failure. As emerging studies have increased in the literature on the role of specific gut microbiota metabolites in heart failure development, this review highlights and summarizes the current evidence and underlying mechanisms associated with the pathogenesis of heart failure. We found that gut microbiota-derived metabolites such as short chain fatty acids, bile acids, branched-chain amino acids, tryptophan and indole derivatives as well as trimethylamine-derived metabolite, trimethylamine N-oxide, play critical roles in promoting heart failure through various mechanisms. Mainly, they modulate complex signaling pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells, Bcl-2 interacting protein 3, NLR Family Pyrin Domain Containing inflammasome, and Protein kinase RNA-like endoplasmic reticulum kinase. We have also highlighted the beneficial role of other gut metabolites in heart failure and other cardiovascular and metabolic diseases.