Brain fog in long COVID limits function and health status, independently of hospital severity and preexisting conditions.

Importance: The U.S. government has named post-acute sequelae of COVID-19 (longCOVID) as influential on disability rates. We previously showed that COVID-19 carries a medical/functional burden at 1 year, and that age and other risk factors of severe COVID-19 were not associated with increased longCOVID risk. Long-term longCOVID brain fog (BF) prevalence, risk factors and associated medical/functional factors are poorly understood, especially after mild SARS-CoV-2 infection. Methods: A retrospective observational cohort study was conducted at an urban tertiary-care hospital. Of 1,032 acute COVID-19 survivors from March 3-May 15, 2020, 633 were called, 530 responded (59.2 ± 16.3 years, 44.5% female, 51.5% non-White) about BF prevalence, other longCOVID, post-acute ED/hospital utilization, perceived health/social network, effort tolerance, disability. Results: At approximately 1-year, 31.9% (n = 169) experienced BF. Acute COVID-19 severity, age, and premorbid cardiopulmonary comorbidities did not differ between those with/without BF at 1 year. Patients with respiratory longCOVID had 54% higher risk of BF than those without respiratory longCOVID. BF associated with sleep disturbance (63% with BF vs.29% without BF, p < 0.0001), shortness of breath (46% vs.18%, p < 0.0001), weakness (49% vs.22%, p < 0.0001), dysosmia/dysgeusia (12% vs.5%, p < 0.004), activity limitations (p < 0.001), disability/leave (11% vs.3%, p < 0.0001), worsened perceived health since acute COVID-19 (66% vs.30%, p < 0.001) and social isolation (40% vs.29%, p < 0.02), despite no differences in premorbid comorbidities and age. Conclusions and relevance: A year after COVID-19 infection, BF persists in a third of patients. COVID-19 severity is not a predictive risk factor. BF associates with other longCOVID and independently associates with persistent debility.

Prevalence and Severity of Chronic Kidney Disease in Haiti.

BACKGROUND: CKD is a major cause of morbidity and mortality in lower-income countries. However, population-based studies characterizing the epidemiology of CKD in these settings are lacking. The study objective was to describe the epidemiology of CKD in a population-based cohort in urban Haiti, including estimates of the prevalence by CKD stage, the magnitude of associated factors with CKD, and the proportion on guideline-recommended treatment. METHODS: We assessed the prevalence of CKD and associated risk factors in the population-based Haiti Cardiovascular Disease Cohort. We analyzed cross-sectional data from 2424 adults who completed a clinical examination, risk factor surveys, and laboratory measurements for serum creatinine, urinary albumin, and urinary creatinine. We compared our results with US estimates from the National Health and Nutrition Examination Survey. CKD was defined as either a reduced eGFR <60 ml/min per 1.73 m 2 or urinary albumin-to-creatinine ratio ≥30 mg/g according to the Kidney Disease Improving Global Outcomes guidelines. Multivariable logistic regression identified associated factors with CKD. RESULTS: The mean age was 42 years, 57% of participants were female, and 69% lived in extreme poverty on ≤1 US dollar per day. The age-standardized prevalence of CKD was 14% (95% confidence interval [CI], 12% to 15%). The age-standardized prevalence of reduced eGFR and elevated urinary albumin-to-creatinine ratio was 3% (95% CI, 2% to 4%) and 11% (95% CI, 10% to 13%), respectively. Diabetes (adjusted odds ratio, 4.1; 95% CI, 2.7 to 6.2) and hypertension (adjusted odds ratio, 2.9; 95% CI, 2.0 to 4.2) were significantly associated with CKD. Only 12% of participants with CKD and albuminuria were on guideline-recommended agents, such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. CONCLUSIONS: In a large population-based cohort of Haitian adults, CKD was highly associated with both diabetes and hypertension. The proportion of participants with CKD on treatment was low, underscoring the need for strengthening clinical management and nephrology care health infrastructure in Haiti. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Longitudinal Cohort Study to Evaluate Cardiovascular Risk Factors and Disease in Haiti, NCT03892265 .

Effects of helminths and anthelmintic treatment on cardiometabolic diseases and risk factors: A systematic review.

BACKGROUND: Globally, helminth infections and cardiometabolic diseases often overlap in populations and individuals. Neither the causal relationship between helminth infections and cardiometabolic diseases nor the effect of helminth eradication on cardiometabolic risk have been reviewed systematically in a large number of human and animal studies. METHODS: We conducted a systematic review assessing the reported effects of helminth infections and anthelmintic treatment on the development and/or severity of cardiometabolic diseases and risk factors. The search was limited to the most prevalent human helminths worldwide. This study followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42021228610). Searches were performed on December 10, 2020 and rerun on March 2, 2022 using Ovid MEDLINE ALL (1946 to March 2, 2022), Web of Science, Cochrane Library, Global Index Medicus, and Ovid Embase (1974 to March 2, 2022). Randomized clinical trials, cohort, cross-sectional, case-control, and animal studies were included. Two reviewers performed screening independently. RESULTS: Eighty-four animal and human studies were included in the final analysis. Most studies reported on lipids (45), metabolic syndrome (38), and diabetes (30), with fewer on blood pressure (18), atherosclerotic cardiovascular disease (11), high-sensitivity C-reactive protein (hsCRP, 5), and non-atherosclerotic cardiovascular disease (4). Fifteen different helminth infections were represented. On average, helminth-infected participants had less dyslipidemia, metabolic syndrome, diabetes, and atherosclerotic cardiovascular disease. Eleven studies examined anthelmintic treatment, of which 9 (82%) reported post-treatment increases in dyslipidemia, metabolic syndrome, and diabetes or glucose levels. Results from animal and human studies were generally consistent. No consistent effects of helminth infections on blood pressure, hsCRP, or cardiac function were reported except some trends towards association of schistosome infection with lower blood pressure. The vast majority of evidence linking helminth infections to lower cardiometabolic diseases was reported in those with schistosome infections. CONCLUSIONS: Helminth infections may offer protection against dyslipidemia, metabolic syndrome, diabetes, and atherosclerotic cardiovascular disease. This protection may lessen after anthelmintic treatment. Our findings highlight the need for mechanistic trials to determine the pathways linking helminth infections with cardiometabolic diseases. Such studies could have implications for helminth eradication campaigns and could generate new strategies to address the global challenge of cardiometabolic diseases.

Population-Based Epidemiology of Heart Failure in a Low-Income Country: The Haiti Cardiovascular Disease Cohort.

BACKGROUND: Cardiovascular disease disproportionately affects persons living in low- and middle-income countries and heart failure (HF) is thought to be a leading cause. Population-based studies characterizing the epidemiology of HF in these settings are lacking. We describe the age-standardized prevalence, survival, subtypes, risk factors, and 1-year mortality of HF in the population-based Haiti Cardiovascular Disease Cohort. METHODS: Participants were recruited using multistage cluster-area random sampling in Port-au-Prince, Haiti. A total of 2981 completed standardized history and exam, laboratory measures, and cardiac imaging. Clinical HF was defined by Framingham criteria. Kaplan-Meier and Cox proportional hazard regression assessed mortality among participants with and without HF; logistic regression identified associated factors. RESULTS: Among all participants, the median age was 40 years (interquartile range, 27-55), and 58.2% were female. Median follow-up was 15.4 months (interquartile range, 9-22). The age-standardized HF prevalence was 3.2% (93/2981 [95% CI, 2.6-3.9]). The average age of participants with HF was 57 years (interquartile range, 45-65), and 67.7% were female. The first significant increase in HF prevalence occurred between 30 to 39 and 40 to 49 years (1.1% versus 3.7%, P=0.003). HF with preserved ejection fraction was the most common HF subtype (71.0%). Age (adjusted odds ratio, 1.36 [1.12-1.66] per 10-year increase), hypertension (2.14 [1.26-3.66]), obesity (3.35 [95% CI, 1.99-5.62]), poverty (2.10 [1.18-3.72]), and renal dysfunction (5.42 [2.94-9.98]) were associated with HF. One-year HF mortality was 6.6% versus 0.8% (hazard ratio, 7.7 [95% CI, 2.9-20.6]; P<0.0001). CONCLUSIONS: The age-standardized prevalence of HF in this low-income setting was alarmingly high at 3.2%-5-fold higher than modeling estimates for low- and middle-income countries. Adults with HF were two decades younger and 7.7× more likely to die at 1 year compared with those in the community without HF. Further research characterizing the population burden of HF in low- and middle-income countries can guide resource allocation and development of pragmatic HF prevention and treatment interventions, ultimately reducing global cardiovascular disease health disparities. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03892265.

Comparing six cardiovascular risk prediction models in Haiti: implications for identifying high-risk individuals for primary prevention.

BACKGROUND: Cardiovascular diseases (CVD) are rapidly increasing in low-middle income countries (LMICs). Accurate risk assessment is essential to reduce premature CVD by targeting primary prevention and risk factor treatment among high-risk groups. Available CVD risk prediction models are built on predominantly Caucasian risk profiles from high-income country populations, and have not been evaluated in LMIC populations. We aimed to compare six existing models for predicted 10-year risk of CVD and identify high-risk groups for targeted prevention and treatment in Haiti. METHODS: We used cross-sectional data within the Haiti CVD Cohort Study, including 1345 adults ≥ 40 years without known history of CVD and with complete data. Six CVD risk prediction models were compared: pooled cohort equations (PCE), adjusted PCE with updated cohorts, Framingham CVD Lipids, Framingham CVD Body Mass Index (BMI), WHO Lipids, and WHO BMI. Risk factors were measured during clinical exams. Primary outcome was continuous and categorical predicted 10-year CVD risk. Secondary outcome was statin eligibility. RESULTS: Sixty percent were female, 66.8% lived on a daily income of ≤ 1 USD, 52.9% had hypertension, 14.9% had hypercholesterolemia, 7.8% had diabetes mellitus, 4.0% were current smokers, and 2.5% had HIV. Predicted 10-year CVD risk ranged from 3.6% in adjusted PCE (IQR 1.7-8.2) to 9.6% in Framingham-BMI (IQR 4.9-18.0), and Spearman rank correlation coefficients ranged from 0.86 to 0.98. The percent of the cohort categorized as high risk using model specific thresholds ranged from 1.8% using the WHO-BMI model to 41.4% in the PCE model (χ2 = 1416, p value < 0.001). Statin eligibility also varied widely. CONCLUSIONS: In the Haiti CVD Cohort, there was substantial variation in the proportion identified as high-risk and statin eligible using existing models, leading to very different treatment recommendations and public health implications depending on which prediction model is chosen. There is a need to design and validate CVD risk prediction tools for low-middle income countries that include locally relevant risk factors. TRIAL REGISTRATION: clinicaltrials.gov NCT03892265 .

Atrial fibrillation and mortality in outpatients with heart failure in Tanzania: a prospective cohort study.

OBJECTIVE: In recent years, the prevalence and mortality of heart failure (HF) and other associated cardiovascular diseases have doubled in sub-Saharan Africa (SSA). Studies in high-income countries indicate that HF with concurrent atrial fibrillation (AF) is linked to increased mortality. Our objective was to determine the incidence and clinical outcomes of AF among patients with HF in SSA. DESIGN: A prospective cohort study using data collected between October 2018 and May 2020. SETTING: Outpatient clinic at a tertiary hospital in Mwanza, Tanzania. PARTICIPANTS: 303 adult participants (aged ≥18 years) with HF as defined by the European Society of Cardiology guidelines (2016) and 100 adults with HF as defined by clinical criteria alone were enrolled into the study. Patients with comorbid medical condition that had prognosis of <3 months (ie, advance solid tumours, advance haematological malignancies) were excluded. METHODS: Participants were screened for AF, and their medical history, physical examinations and sociodemographic information were obtained. Multivariable logistic regression models were used to examine factors associated with AF incidence. Cox regression models were used to analyse 3-month mortality and its associated risk factors. RESULTS: We enrolled 403 participants with HF (mean age 60±19 years, 234 (58%) female). The AF prevalence was 17%. In multivariable models, factors associated with AF were low income, alcohol consumption and longer duration of HF. At the end of the 3-month follow-up, 120 out of 403 (30%) participants died, including 44% (31/70) of those with AF. Higher heart rate on ECG, more severe New York Heart Association HF class, rural residence and anaemia were significantly correlated with mortality. CONCLUSION: AF is common, underdiagnosed and is associated with significant mortality among outpatients with HF in Tanzania (HR 1.749, 95% CI 1.162 to 2.633, p=0.007). Our findings additionally identify tachycardia (>110 bpm, HR 1.879, 95% CI 1.508 to 2.340, p<0.001) as an easily measurable, high-impact physical examination finding for adverse outcomes in patients with HF.

Health Status, Persistent Symptoms, and Effort Intolerance One Year After Acute COVID-19 Infection.

BACKGROUND: The long-term prevalence and risk factors for post-acute COVID-19 sequelae (PASC) are not well described and may have important implications for unvaccinated populations and policy makers. OBJECTIVE: To assess health status, persistent symptoms, and effort tolerance approximately 1 year after COVID-19 infection DESIGN: Retrospective observational cohort study using surveys and clinical data PARTICIPANTS: Survey respondents who were survivors of acute COVID-19 infection requiring Emergency Department presentation or hospitalization between March 3 and May 15, 2020. MAIN MEASURE(S): Self-reported health status, persistent symptoms, and effort tolerance KEY RESULTS: The 530 respondents (median time between hospital presentation and survey 332 days [IQR 325-344]) had mean age 59.2±16.3 years, 44.5% were female and 70.8% were non-White. Of these, 41.5% reported worse health compared to a year prior, 44.2% reported persistent symptoms, 36.2% reported limitations in lifting/carrying groceries, 35.5% reported limitations climbing one flight of stairs, 38.1% reported limitations bending/kneeling/stooping, and 22.1% reported limitations walking one block. Even those without high-risk comorbid conditions and those seen only in the Emergency Department (but not hospitalized) experienced significant deterioration in health, persistent symptoms, and limitations in effort tolerance. Women (adjusted relative risk ratio [aRRR] 1.26, 95% CI 1.01-1.56), those requiring mechanical ventilation (aRRR 1.48, 1.02-2.14), and people with HIV (aRRR 1.75, 1.14-2.69) were significantly more likely to report persistent symptoms. Age and other risk factors for more severe COVID-19 illness were not associated with increased risk of PASC. CONCLUSIONS: PASC may be extraordinarily common 1 year after COVID-19, and these symptoms are sufficiently severe to impact the daily exercise tolerance of patients. PASC symptoms are broadly distributed, are not limited to one specific patient group, and appear to be unrelated to age. These data have implications for vaccine hesitant individuals, policy makers, and physicians managing the emerging longer-term yet unknown impact of the COVID-19 pandemic.

Schistosoma mansoni Infection Is Associated With Increased Monocytes and Fewer Natural Killer T Cells in the Female Genital Tract.

Schistosoma mansoni infection may impair genital mucosal antiviral immunity, but immune cell populations have not been well characterized. We characterized mononuclear cells from cervical brushings of women with and without S mansoni infection. We observed lower frequencies of natural killer T cells and higher frequencies of CD14+ monocytes in infected women.

Thirty-Day Post-Discharge Outcomes Following COVID-19 Infection.

BACKGROUND: The clinical course of COVID-19 includes multiple disease phases. Data describing post-hospital discharge outcomes may provide insight into disease course. Studies describing post-hospitalization outcomes of adults following COVID-19 infection are limited to electronic medical record review, which may underestimate the incidence of outcomes. OBJECTIVE: To determine 30-day post-hospitalization outcomes following COVID-19 infection. DESIGN: Retrospective cohort study SETTING: Quaternary referral hospital and community hospital in New York City. PARTICIPANTS: COVID-19 infected patients discharged alive from the emergency department (ED) or hospital between March 3 and May 15, 2020. MEASUREMENT: Outcomes included return to an ED, re-hospitalization, and mortality within 30 days of hospital discharge. RESULTS: Thirty-day follow-up data were successfully collected on 94.6% of eligible patients. Among 1344 patients, 16.5% returned to an ED, 9.8% were re-hospitalized, and 2.4% died. Among patients who returned to the ED, 50.0% (108/216) went to a different hospital from the hospital of the index presentation, and 61.1% (132/216) of those who returned were re-hospitalized. In Cox models adjusted for variables selected using the lasso method, age (HR 1.01 per year [95% CI 1.00-1.02]), diabetes (1.54 [1.06-2.23]), and the need for inpatient dialysis (3.78 [2.23-6.43]) during the index presentation were independently associated with a higher re-hospitalization rate. Older age (HR 1.08 [1.05-1.11]) and Asian race (2.89 [1.27-6.61]) were significantly associated with mortality. CONCLUSIONS: Among patients discharged alive following their index presentation for COVID-19, risk for returning to a hospital within 30 days of discharge was substantial. These patients merit close post-discharge follow-up to optimize outcomes.

Nocturnal dipping of heart rate and blood pressure in people with HIV in Tanzania.

People with HIV (PWH) have a >2-fold greater risk for development of cardiovascular disease (CVD), which may be associated with abnormalities in 24-h ambulatory blood pressure measurement (ABPM) profile. We conducted a nested case-control study of ABPM in 137 PWH and HIV-uninfected controls with normal and high clinic blood pressure (BP) in Tanzania. Nocturnal non-dipping of heart rate (HR) was significantly more common among PWH than HIV-uninfected controls (p = .01). Nocturnal non-dipping of BP was significantly more common in PWH with normal clinic BP (p = .048). Clinical correlates of nocturnal non-dipping were similar in PWH and HIV-uninfected adults and included higher BMI, higher CD4+ cell count, and high C-reactive protein for HR and markers of renal disease for BP. In conclusion, nocturnal non-dipping of both BP and HR was more common in PWH but further research is needed to determine causes and consequences of this difference.

COVID-19-Related Circumstances for Hospital Readmissions: A Case Series From 2 New York City Hospitals.

OBJECTIVE: The aim of the study was to determine the main factors contributing to hospital readmissions and their potential preventability after a coronavirus disease 2019 (COVID-19) hospitalization at 2 New York City hospitals. METHODS: This was a retrospective study at 2 affiliated New York City hospitals located in the Upper East Side and Lower Manhattan neighborhoods. We performed case reviews using the Hospital Medicine Reengineering Network framework to determine potentially preventable readmissions among patients hospitalized for COVID-19 between March 3, 2020 (date of first case) and April 27, 2020, and readmitted to either of the 2 hospitals within 30 days of discharge. RESULTS: Among 53 readmissions after hospitalization for COVID-19, 44 (83%) were deemed not preventable and 9 (17%) were potentially preventable. Nonpreventable readmissions were mostly due to disease progression or complications of COVID-19 (37/44, 84%). Main factors contributing to potentially preventable readmissions were issues with initial disposition (5/9, 56%), premature discharge (3/9, 33%), and inappropriate readmission (1/9, 11%) for someone who likely did not require rehospitalization. CONCLUSIONS: Most readmissions after a COVID-19 hospitalization were not preventable and a consequence of the natural progression of the disease, specifically worsening dyspnea or hypoxemia. Some readmissions were potentially preventable, mostly because of issues with disposition that were directly related to challenges posed by the ongoing COVID-19 pandemic. Clinicians should be aware of challenges with disposition related to circumstances of the COVID-19 pandemic.

Human Immunodeficiency Virus-Associated Myocardial Diastolic Dysfunction and Soluble ST2 Concentration in Tanzanian Adults: A Cross-Sectional Study.

BACKGROUND: The aims of this study were (1) to compare the prevalence of myocardial diastolic dysfunction (DD) in antiretroviral therapy (ART)-naive people living with human immunodeficiency virus (PLWH) to human immunodeficiency virus (HIV)-uninfected adults in East Africa and (2) to determine the association between serum concentration of the cardiac biomarkers ST2 and DD. METHODS: In this cross-sectional study, we enrolled PLWH and uninfected adults at a referral HIV clinic in Mwanza, Tanzania. Standardized history, echocardiography, and serum were obtained. Regression models were used to quantify associations. RESULTS: We enrolled 388 ART-naive PLWH and 461 HIV-uninfected adults with an average age of 36.0 ± 10.2 years. Of PLWH in the third, fourth, and fifth decades of life, 5.0%, 12.5%, and 32.7%, respectively, had DD. PLWH had a higher prevalence of DD (adjusted odds ratio, 2.71 [95% confidence interval, 1.62-4.55]; P < .0001). PLWH also had a higher probability of dysfunction with one or fewer traditional risk factors present. Serum ST2 concentration was associated with dysfunction in PLWH but not uninfected participants (P = .04 and P = .90, respectively). CONCLUSIONS: In a large population of young adults in sub-Saharan Africa, DD prevalence increased starting in the third decade of life. HIV was independently associated with dysfunction. Serum ST2 concentration was associated with DD in PLWH but not HIV-uninfected participants. This pathway may provide insight into the mechanisms of HIV-associated dysfunction.

The burden of HIV, syphilis and schistosome infection and associated factors among adults in the fishing communities in northwestern Tanzania.

OBJECTIVES: To quantify the burden of HIV, syphilis and schistosome infection and associated risk factors among adults living in seven fishing communities of Lake Victoria in northwest Tanzania. METHODS: Cross-sectional study conducted between 2015 and 2016 in the selected communities. In each community, we randomly selected a sample of adults from the general population and from three putative risk groups including the following: (i) fishermen, (ii) fish processors and traders, and (iii) women working in the recreational facilities. Participants were interviewed to obtain information about potential risk factors, and venous blood was collected for detection of HIV, syphilis and schistosome infections. We used logistic regression models to quantify the associations between potential risk factors and HIV, and also between schistosome infection and HIV. RESULTS: We enrolled 1128 people from selected fishing communities. The overall prevalence of HIV, syphilis and schistosome infection was 14.2%, 15.6% and 83.1%, respectively. Female recreational facility workers had the highest prevalence of HIV (30.4%) and syphilis (24%). The odds of being HIV infected were generally higher in all age categories. Transactional sex was commonly reported and especially receiving gifts for sex was found to be strongly associated with HIV (adjusted OR = 2.50; 95% CI: 1.44-4.34, P = 0.008). Confirmed serological syphilis was associated with increased odds of having HIV infection. HIV was not associated with schistosome infection in a combined dataset and when we examined this separately for men and women alone. CONCLUSIONS: We observed a high burden of HIV, syphilis and schistosome infections in the fishing communities. Targeted efforts to treat and control infections have the potential to improve health among their residents.

OBJECTIFS: Quantifier la charge du VIH, de la syphilis et de l'infection à schistosomes et les facteurs de risque associés chez les adultes vivant dans sept communautés de pêcheurs du lac Victoria dans le nord-ouest de la Tanzanie. MÉTHODES: Etude transversale menée entre 2015-2016 dans les communautés sélectionnées. Dans chaque communauté, nous avons sélectionné aléatoirement un échantillon d'adultes de la population générale et de trois groupes à risque présumés, notamment: 1) les pêcheurs, 2) les transformateurs et commerçants de poisson et 3) les femmes travaillant dans les établissements de loisirs. Les participants ont été interrogés pour obtenir des informations sur les facteurs de risque potentiels, et du sang veineux a été collecté pour la détection du VIH, de la syphilis et des infections à schistosome. Nous avons utilisé des modèles de régression logistique pour quantifier les associations entre les facteurs de risque potentiels et le VIH, ainsi qu'entre l'infection à schistosome et le VIH. RÉSULTATS: Nous avons recruté 1.128 personnes dans une sélection de communautés de pêcheurs. La prévalence globale de l'infection par le VIH, la syphilis et les schistosomes était de 14,2%, 15,6% et 83,1% respectivement. Les travailleuses des établissements de loisirs avaient la prévalence la plus élevée du VIH (30,4%) et de la syphilis (24%). Les chances d'être infecté par le VIH étaient généralement plus élevées dans toutes les catégories d'âge. Les rapports sexuels transactionnels étaient fréquemment rapportés et surtout le fait de recevoir des cadeaux pour le sexe était fortement associé au VIH (OR ajusté = 2,50; IC95%: 1,44-4,34 ; P = 0,008). La syphilis sérologique confirmée était associée à une probabilité accrue d'être infecté par le VIH. Le VIH n'était pas associé à une infection à schistosome dans un ensemble de données combinées et lorsque nous avons examiné cela séparément pour les hommes et les femmes. CONCLUSIONS: Nous avons observé une charge élevée d'infections par le VIH, la syphilis et les schistosomes dans les communautés de pêcheurs. Des efforts ciblés pour traiter et contrôler les infections ont le potentiel d'améliorer la santé des résidents.

Heart failure, post-hospital mortality and renal function in Tanzania: A prospective cohort study.

OBJECTIVE: To determine one-year, post-hospital mortality and the predictors of mortality in Tanzanian adults with heart failure (HF) compared to other admitted adults. METHODS: In this prospective cohort study we consecutively enrolled medical inpatients admitted during a 3-month period, screened for HF and followed until 12 months after hospital discharge. Standardized history, physical examination, echocardiography and laboratory investigations were obtained during hospital presentation. The primary outcome was one-year post-discharge mortality. The secondary outcome was in-hospital mortality. Cox regression adjusted for age and sex was used. RESULTS: During the study period, we enrolled 558 adults; 145 had HF and 107 of these survived until discharge. Patients with HF had a higher one-year post-hospital discharge mortality than all other diagnoses (62/107 (57.9%) vs 150/343 (43.7%), respectively, HR=1.57[1.13-2.18]). In-hospital mortality was similar. Markers of renal disease were more common in adults with HF (40/107 (37.4%) and were the strongest independent predictors of post-hospital mortality: low eGFR (HR=2.94[1.62-5.31]) and proteinuria (HR=2.03, [95%CI 1.13-3.66]). No patients discharged with the combination of low eGFR/proteinuria survived to the one-year endpoint. Of note, 79/145 (54.5%) of adults admitted with HF were newly diagnosed during hospital admission. CONCLUSIONS: Over half of adults discharged with HF died within 12months after discharge. Adults with HF had higher post-hospital mortality compared to other medical inpatients. Markers of renal disease were the strongest predictor of this mortality. Innovative interventions are needed to reduce post-hospital mortality in adults with HF and should focus on those with renal disease.

Leukocyte iNOS is required for inflammation and pathological remodeling in ischemic heart failure.

In the failing heart, iNOS is expressed by both macrophages and cardiomyocytes. We hypothesized that inflammatory cell-localized iNOS exacerbates left ventricular (LV) remodeling. Wild-type (WT) C57BL/6 mice underwent total body irradiation and reconstitution with bone marrow from iNOS-/- mice (iNOS-/-c) or WT mice (WTc). Chimeric mice underwent coronary ligation to induce large infarction and ischemic heart failure (HF), or sham surgery. After 28 days, as compared with WTc sham mice, WTc HF mice exhibited significant (p < 0.05) mortality, LV dysfunction, hypertrophy, fibrosis, oxidative/nitrative stress, inflammatory activation, and iNOS upregulation. These mice also exhibited a ~twofold increase in circulating Ly6Chi pro-inflammatory monocytes, and ~sevenfold higher cardiac M1 macrophages, which were primarily CCR2- cells. In contrast, as compared with WTc HF mice, iNOS-/-c HF mice exhibited significantly improved survival, LV function, hypertrophy, fibrosis, oxidative/nitrative stress, and inflammatory activation, without differences in overall cardiac iNOS expression. Moreover, iNOS-/-c HF mice exhibited lower circulating Ly6Chi monocytes, and augmented cardiac M2 macrophages, but with greater infiltrating monocyte-derived CCR2+ macrophages vs. WTc HF mice. Lastly, upon cell-to-cell contact with naïve cardiomyocytes, peritoneal macrophages from WT HF mice depressed contraction, and augmented cardiomyocyte oxygen free radicals and peroxynitrite. These effects were not observed upon contact with macrophages from iNOS-/- HF mice. We conclude that leukocyte iNOS is obligatory for local and systemic inflammatory activation and cardiac remodeling in ischemic HF. Activated macrophages in HF may directly induce cardiomyocyte contractile dysfunction and oxidant stress upon cell-to-cell contact; this juxtacrine response requires macrophage-localized iNOS.

Short-term and long-term cardiovascular risk, metabolic syndrome and HIV in Tanzania.

OBJECTIVE: To compare short-term and long-term cardiovascular disease (CVD) risk scores and prevalence of metabolic syndrome in HIV-infected adults receiving and not receiving antiretroviral therapy (ART) to HIV-negative controls. METHODS: A cross-sectional study including 151 HIV-infected, ART-naive, 150 HIV-infected on ART and 153 HIV-negative adults. Traditional cardiovascular risk factors were determined by standard investigations. The primary outcome was American College of Cardiology/American Heart Association Atherosclerotic CVD (ASCVD) Risk Estimator lifetime CVD risk score. Secondary outcomes were ASCVD 10-year risk, Framingham risk scores, statin indication and metabolic syndrome. RESULTS: Compared with HIV-negative controls, more HIV-infected adults on ART were classified as high lifetime CVD risk (34.7% vs 17.0%, p<0.001) although 10-year risk scores were similar, a trend which was similar across multiple CVD risk models. In addition, HIV-infected adults on ART had a higher prevalence of metabolic syndrome versus HIV-negative controls (21.3% vs 7.8%, p=0.008), with two common clusters of risk factors. More than one-quarter (28.7%) of HIV-infected Tanzanian adults on ART meet criteria for statin initiation. CONCLUSIONS: HIV-infected ART-treated individuals have high lifetime cardiovascular risk, and this risk seems to develop rapidly in the first 3-4 years of ART as does the development of clusters of metabolic syndrome criteria. These data identify a new subgroup of low short-term/high-lifetime risk HIV-infected individuals on ART who do not currently meet criteria for CVD risk factor modification but require further study.

Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure: critical importance of the cardiosplenic axis.

RATIONALE: The role of mononuclear phagocytes in chronic heart failure (HF) is unknown. OBJECTIVE: Our aim was to delineate monocyte, macrophage, and dendritic cell trafficking in HF and define the contribution of the spleen to cardiac remodeling. METHODS AND RESULTS: We evaluated C57Bl/6 mice with chronic HF 8 weeks after coronary ligation. As compared with sham-operated controls, HF mice exhibited: (1) increased proinflammatory CD11b+ F4/80+ CD206- macrophages and CD11b+ F4/80+ Gr-1(hi) monocytes in the heart and peripheral blood, respectively, and reduced CD11b+ F4/80+ Gr-1(hi) monocytes in the spleen; (2) significantly increased CD11c+ B220- classical dendritic cells and CD11c+ low)B220+ plasmacytoid dendritic cells in both the heart and spleen, and increased classic dendritic cells and plasmacytoid dendritic cells in peripheral blood and bone marrow, respectively; (3) increased CD4+ helper and CD8+ cytotoxic T-cells in the spleen; and (4) profound splenic remodeling with abundant white pulp follicles, markedly increased size of the marginal zone and germinal centers, and increased expression of alarmins. Splenectomy in mice with established HF reversed pathological cardiac remodeling and inflammation. Splenocytes adoptively transferred from mice with HF, but not from sham-operated mice, homed to the heart and induced long-term left ventricular dilatation, dysfunction, and fibrosis in naive recipients. Recipient mice also exhibited monocyte activation and splenic remodeling similar to HF mice. CONCLUSIONS: Activation of mononuclear phagocytes is central to the progression of cardiac remodeling in HF, and heightened antigen processing in the spleen plays a critical role in this process. Splenocytes (presumably splenic monocytes and dendritic cells) promote immune-mediated injurious responses in the failing heart and retain this memory on adoptive transfer.