Proteomic Profiling in Patients With Peripartum Cardiomyopathy: A Biomarker Study of the ESC EORP PPCM Registry.

BACKGROUND: Peripartum cardiomyopathy (PPCM) remains an important cause of maternal morbidity and mortality globally. The pathophysiology remains incompletely understood, and the diagnosis is often missed or delayed. OBJECTIVES: This study explored the serum proteome profile of patients with newly diagnosed PPCM, as compared with matched healthy postpartum mothers, to unravel novel protein biomarkers that would further an understanding of the pathogenesis of PPCM and improve diagnostic precision. METHODS: Study investigators performed untargeted serum proteome profiling using data-independent acquisition-based label-free quantitative liquid chromatography-tandem mass spectrometry on 84 patients with PPCM, as compared with 29 postpartum healthy controls (HCs). Significant changes in protein intensities were determined with nonpaired Student's t-tests and were further classified by using the Boruta algorithm. The proteins' diagnostic performance was evaluated by area under the curve (AUC) and validated using the 10-fold cross-validation. RESULTS: Patients with PPCM presented with a mean left ventricular ejection fraction of 33.5% ± 9.3% vs 57.0% ± 8.8% in HCs (P < 0.001). Study investigators identified 15 differentially up-regulated and 14 down-regulated proteins in patients with PPCM compared with HCs. Seven of these proteins were recognized as significant by the Boruta algorithm. The combination of adiponectin, quiescin sulfhydryl oxidase 1, inter-α-trypsin inhibitor heavy chain, and N-terminal pro-B-type natriuretic peptide had the best diagnostic precision (AUC: 0.90; 95% CI: 0.84-0.96) to distinguish patients with PPCM from HCs. CONCLUSIONS: Salient biologic themes related to immune response proteins, inflammation, fibrosis, angiogenesis, apoptosis, and coagulation were predominant in patients with PPCM compared with HCs. These newly identified proteins warrant further evaluation to establish their role in the pathogenesis of PPCM and potential use as diagnostic markers.

Long-Term Follow-up of Human Immunodeficiency Virus-Associated Pulmonary Hypertension: Clinical Features and Survival Outcomes of the Pan Africa Pulmonary Hypertension Cohort (PAPUCO).

Background: Data characterizing risk factors and long-term outcome studies on human immunodeficiency virus (HIV)-associated pulmonary hypertension (PH) in Africa are lacking. Methods: The Pan African Pulmonary Hypertension Cohort, a multinational registry of 254 consecutive patients diagnosed with PH (97% of African descent) from 9 centers in 4 African countries was implemented. We compared baseline characteristics and 3-year survival of an HIV-infected cohort newly diagnosed with PH (PH/HIV+) to an HIV-uninfected cohort with PH (PH/HIV-). Results: One hundred thirty-four participants with PH completed follow up (47 PH/HIV+ and 87 PH/HIV-; age median, 36 versus 44 years; P = .0004). Cardiovascular risk factors and comorbidities were similar except for previous tuberculosis (62% versus 18%, P < .0001). Six-minute walk distance (6MWD) <300 meters was common in PH/HIV- (P = .0030), but PH/HIV+ had higher heart (P = .0160) and respiratory (P = .0374) rates. Thirty-six percent of PH/HIV+ and 15% of PH/HIV- presented with pulmonary arterial hypertension (PAH) (P = .0084), whereas 36% of PH/HIV+ and 72% of PH/HIV- exhibited PH due to left heart disease (PHLHD) (P = .0009). Pulmonary hypertension due to lung diseases and hypoxia (PHLD) was frequent in PH/HIV+ (36% versus 15%) but did not reach statistical significance. Human immunodeficiency virus-associated PAH tended to have a poorer survival rate compared with PHLHD/PHLD in HIV-infected patients. Conclusions: The PH/HIV + patients were younger and commonly had previous tuberculosis compared to PH/HIV- patients. Despite a better 6MWD at presentation, they had more signs and symptoms of early onset heart failure and a worse survival rate. Early echocardiography assessment should be performed in HIV-infected patients with history of tuberculosis who present with signs and symptoms of heart failure or posttuberculosis lung disease.

Role of pregnancy hormones and hormonal interaction on the maternal cardiovascular system: a literature review.

Hormones have a vital duty in the conservation of physiological cardiovascular function during pregnancy. Alterations in oestrogen, progesterone and prolactin levels are associated with changes in the cardiovascular system to support the growing foetus and counteract pregnancy stresses. Pregnancy hormones are, however, also linked to numerous pathophysiological outcomes on the cardiovascular system. The expression and effects of the three main pregnancy hormones (oestrogen, prolactin and progesterone) vary depending on the gestation period. However, the reaction of a target cell also depends on the abundance of hormone receptors and impacts put forth by other hormones. Hormonal interaction may be synergistic, antagonistic or permissive. It is crucial to explore the cross talk of pregnancy hormones during gestation, as this may have a greater impact on the overall changes to the cardiovascular system.

Apolipoprotein B Gene Polymorphisms and Dyslipidemia in HIV Infected Adult Zimbabweans.

BACKGROUND: Dyslipidemia does not occur in all HIV-infected or antiretroviral therapy-experienced patients suggesting role of host genetic factors but there is paucity of data on association between dyslipidemia and gene polymorphisms in Zimbabwe. OBJECTIVE: To determine association of lipoprotein levels and apolipoprotein B polymorphisms in HIV-infected adults. METHOD: Demographic data were collected from 103 consenting patients; lipoprotein levels were determined and blood samples were successfully genotyped for both apolipoprotein B 2488C>T Xba1 and apolipoprotein B 4154G>A p.Gln4154Lys EcoR1 polymorphisms by real time polymerase chain reaction. RESULTS: Mean age of genotyped patients was 40.3 ± 10.1 years, 68% were female; prevalence of dyslipidemia was 67.4%. Of 103 samples genotyped for apolipoprotein B Xba1 polymorphism, 76 (74%) were homozygous C/C, 24 (23%) were heterozygous C/T and only three (3%) were homozygous T/T. Apolipoprotein B EcoR1 polymorphism showed little variability, one participant had rare genotype A/A, 68.3% had wild type genotype G/G. CONCLUSION: Observed frequencies of apolipoprotein B XbaI and EcoRI polymorphisms matched other African studies. In spite of low numbers of rare variants, there was positive association between both total cholestrol and high density lipoprotein with ECoR1 wild type G/G genotype, suggesting that ECoRI 4154 G allele could be more protective against coronary heart disease than EcoR1 4154 A allele. There is need for further research at population level to confirm whether apolipoprotein B ECoR1 genotyping is useful for predicting risk of dyslipidemia in HIV patients in our setting.

Changes in Lipid Profiles of HIV(+) Adults over Nine Months at a Harare HIV Clinic: A Longitudinal Study.

HIV infection, together with ART, is associated with changes in biochemical, metabolic parameters and lipid profiles. The aim of this study was to compare changes in lipid profiles among HIV positive outpatients over nine months. 171 patients were investigated, 79% were ART experienced, and 82% of ART experienced patients were on NVP/EFV first line at baseline, but some patients changed ART groups over follow-up and classification was based on intent to treat. More than 60% ART naïve and ART experienced patients had some form of dyslipidemia either at baseline or at follow-up, but mean lipid values for the two groups were within normal limits. At baseline and follow-up, mean levels of TC and HDL were slightly higher in the ART experienced group. Interestingly, there was higher increase in HDL over time in the ART negative group compared to the ART positive group. There was a decrease in TC/HDL ratio in both groups over time, suggesting a reduction in calculated risk of CHD over time. HIV positive patients frequently show various forms of dyslipidemia, but there are no changes in average atherogenic lipid levels and results suggest reduced risk of CHD, mainly due to increases in HDL, after nine months of observation time.

Dyslipidemia and cardiovascular disease risk profiles of patients attending an HIV treatment clinic in Harare, Zimbabwe.

The chronic inflammation induced by human immunodeficiency virus (HIV) contributes to increased risk of coronary heart disease (CHD) in HIV-infected individuals. HIV-infected patients generally benefit from being treated with antiretroviral drugs, but some antiretroviral agents have side effects, such as dyslipidemia and hyperglycemia. There is general consensus that antiretroviral drugs induce a long-term risk of CHD, although the levels of that risk are somewhat controversial. The intention of this cross-sectional study was to describe the lipid profile and the long-term risk of CHD among HIV-positive outpatients at an HIV treatment clinic in Harare, Zimbabwe. Two hundred and fifteen patients were investigated (females n=165, mean age 39.8 years; males n=50; mean age 42.0 years). Thirty of the individuals were antiretroviral-naïve and 185 had been on antiretroviral therapy (ART) for a mean 3.9±3.4 years. All participants had average lipid and glucose values within normal ranges, but there was a small difference between the ART and ART-for total cholesterol (TC) and high-density lipoprotein (HDL). Those on a combination of D4T or ZDV/NVP/3TC and PI-based ART were on average oldest and had the highest TC levels. Framingham risk showed 1.4% prevalence of high CHD risk within the next ten years. After univariate analysis age, sex, TC/HDL ratio, HDL, economic earnings and systolic BP were associated with medium to high risk of CHD. After multivariate regression analysis and adjusting for age or sex only age, sex and economic earnings were associated with medium to high risk of CHD. There is small risk of developing CHD, during the next decade in HIV infected patients at an HIV treatment clinic in Harare.