Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT:

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.

SUBMITTER: Kingery JR

PROVIDER: S-EPMC7781450 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Immune Correlates of Diffuse Myocardial Fibrosis and Diastolic Dysfunction Among Aging Women With Human Immunodeficiency Virus.

Project description:Human immunodeficiency virus (HIV) imparts increased heart failure risk to women. Among women with HIV (WHIV), immune pathways relating to heart failure precursors may intimate targets for heart failure prevention strategies. Twenty asymptomatic, antiretroviral-treated WHIV and 14 non-HIV-infected women matched on age and body mass index underwent cardiac magnetic resonance imaging and immune phenotyping. WHIV (vs non-HIV-infected women) exhibited increased myocardial fibrosis (extracellular volume fraction, 0.34 ± 0.06 vs 0.29 ± 0.04; P = .002), reduced diastolic function (diastolic strain rate, 1.10 ± 0.23 s-1 vs 1.39 ± 0.27 s-1; P = .003), and heightened systemic monocyte activation. Among WHIV, soluble CD163 levels correlated with myocardial fibrosis (r = 0.53; P = .02), while circulating inflammatory CD14+CD16+ monocyte CCR2 expression related directly to myocardial fibrosis (r = 0.48; P = .04) and inversely to diastolic function (r = -0.49; P = .03). Clinical Trials Registration. NCT02874703.

| S-EPMC7325805 | biostudies-literature

The Prognostic Value of Soluble ST2 in Adults with Pulmonary Hypertension.

Project description:Soluble ST2 (sST2) is upregulated in response to myocardial stress and may serve as biomarker in adults with pulmonary hypertension (PH). This prospective cohort study investigated sST2 levels and its association with echocardiographic and hemodynamic measures, and adverse clinical outcomes in adults with PH of different etiologies. sST2 was measured during the diagnostic right heart catheterization for PH, in adult patients enrolled between May 2012 and October 2016. PH due to left heart failure was excluded. The association between sST2 and a primary endpoint composed of death or lung transplantation and a secondary composite endpoint including death, lung transplantation or heart failure, was investigated using Cox regression with adjustment for NT-proBNP. In total 104 patients were included (median age was 59 years, 66% woman, 51% pulmonary arterial hypertension). Median sST2 was 28 [IQR 20-46] ng/mL. Higher sST2 was associated with worse right ventricular dysfunction and higher mean pulmonary and right atrial pressures. Median follow-up was 3.3 [IQR 2.3-4.6] years. The primary and secondary endpoint occurred in 33 (31.7%) and 43 (41.3%) patients, respectively. sST2 was significantly associated with both endpoints (HR per 2-fold higher value 1.53, 95%CI 1.12-2.07, p = 0.007 and 1.45, 95%CI 1.10-1.90, p = 0.008, respectively). However, after adjustment for NT-proBNP, both associations did not reach statistical significance. In conclusions, higher sST2 levels are associated with more severe PH and right ventricular dysfunction and yields prognostic value in adults with PH, although not independently of NT-proBNP.

| S-EPMC6832164 | biostudies-literature

Decrease in membrane phospholipids unsaturation correlates with myocardial diastolic dysfunction.

Project description:Increase in saturated fatty acid (SFA) content in membrane phospholipids dramatically affects membrane properties and cellular functioning. We sought to determine whether exogenous SFA from the diet directly affects the degree of membrane phospholipid unsaturation in adult hearts and if these changes correlate with contractile dysfunction. Although both SFA-rich high fat diets (HFDs) and monounsaturated FA (MUFA)-rich HFDs cause the same degree of activation of myocardial FA uptake, triglyceride turnover, and mitochondrial FA oxidation and accumulation of toxic lipid intermediates, the former induced more severe diastolic dysfunction than the latter, which was accompanied with a decrease in membrane phospholipid unsaturation, induction of unfolded protein response (UPR), and a decrease in the expression of Sirt1 and stearoyl-CoA desaturase-1 (SCD1), catalyzing the conversion of SFA to MUFA. When the SFA supply in the heart overwhelms the cellular capacity to use it for energy, excess exogenous SFA channels to membrane phospholipids, leading to UPR induction, and development of diastolic dysfunction.

| S-EPMC6289418 | biostudies-literature

Left ventricular diastolic dysfunction during acute myocardial infarction: effect of mild hypothermia.

Project description:BackgroundMild hypothermia (MH) decreases infarct size and mortality in experimental reperfused myocardial infarction, but may potentiate ischaemia-induced left ventricular (LV) diastolic dysfunction.MethodsIn anaesthetized pigs (70 ± 2 kg), polystyrol microspheres (45 ?m) were infused repeatedly into the left circumflex artery until cardiac power output decreased >40%. Then, pigs were assigned to normothermia (NT, 38.0°C, n=8) or MH (33.0°C, n=8, intravascular cooling) and followed for 6h (CME 6h). p<0.05 vs baseline, †p<0.05 vs NT.ResultsIn NT, cardiac output (CO) decreased from 6.2 ± 0.3 to 3.4 ± 0.2 l/min, and heart rate increased from 89 ± 4 to 101 ± 6 bpm. LV end-diastolic volume fell from 139 ± 8 to 64 ± 4 ml, while LV ejection fraction remained constant (49 ± 1 vs 53 ± 4%). The corresponding end-diastolic pressure-volume relationship was progressively shifted leftwards, reflecting severe LV diastolic dysfunction. In MH, CO fell to a similar degree. Spontaneous bradycardia compensated for slowed LV relaxation, and the leftward shift of the end-diastolic pressure-volume relationship was less pronounced during MH. MH increased systemic vascular resistance, such that mean aortic pressure remained higher in MH vs NT (69 ± 2† vs 54 ± 4 mm Hg). Mixed venous oxygen saturation at CME 6h was higher in MH than in NT (59 ± 4† vs 42 ± 2%) due to lowered systemic oxygen demand during cooling.ConclusionWe conclude that (i) an acute loss of end-diastolic LV compliance is a major component of acute cardiac pump failure during experimental myocardial infarction, and that (ii) MH does not potentiate this diastolic LV failure, but stabilizes haemodynamics and improves systemic oxygen supply/demand imbalance by reducing demand.

| S-EPMC3500695 | biostudies-literature

Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia.

Project description:Sickle cell anemia (SCA)-related cardiomyopathy is characterized by diastolic dysfunction and hyperdynamic features. Diastolic dysfunction portends early mortality in SCA. Diastolic dysfunction is associated with microscopic myocardial fibrosis in SCA mice, but the cause of diastolic dysfunction in humans with SCA is unknown. We used cardiac magnetic resonance measurements of extracellular volume fraction (ECV) to discover and quantify diffuse myocardial fibrosis in 25 individuals with SCA (mean age, 23 ± 13 years) and determine the association between diffuse myocardial fibrosis and diastolic dysfunction. ECV was calculated from pre- and post-gadolinium T1 measurements of blood and myocardium, and diastolic function was assessed by echocardiography. ECV was markedly increased in all participants compared with controls (0.44 ± 0.08 vs 0.26 ± 0.02, P < .0001), indicating the presence of diffuse myocardial fibrosis. Seventeen patients (71%) had diastolic abnormalities, and 7 patients (29%) met the definition of diastolic dysfunction. Participants with diastolic dysfunction had higher ECV (0.49 ± 0.07 vs 0.37 ± 0.04, P = .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; 191 ± 261 vs 33 ± 33 pg/mL, P = .04) but lower hemoglobin (8.4 ± 0.3 vs 10.9 ± 1.4 g/dL, P = .004) compared with participants with normal diastolic function. Participants with the highest ECV values (≥0.40) were more likely to have diastolic dysfunction (P = .003) and increased left atrial volume (57 ± 11 vs 46 ± 12 mL/m2, P = .04) compared with those with ECV <0.4. ECV correlated with hemoglobin (r = -0.46, P = .03) and NT-proBNP (r = 0.62, P = .001). In conclusion, diffuse myocardial fibrosis, determined by ECV, is a common and previously underappreciated feature of SCA that is associated with diastolic dysfunction, anemia, and high NT-proBNP. Diffuse myocardial fibrosis is a novel mechanism that appears to underlie diastolic dysfunction in SCA.

| S-EPMC5510791 | biostudies-literature

Serum PINP, PIIINP, galectin-3, and ST2 as surrogates of myocardial fibrosis and echocardiographic left venticular diastolic filling properties.

Project description:Objectives and backgroundSerum biomarkers have been proposed to reflect fibrosis of several human tissues, but their specific role in the detection of myocardial fibrosis has not been well-established. We studied the association between N-terminal propeptide of type I and III procollagen (PINP, PIIINP, respectively), galectin-3 (gal-3), soluble ST2 (ST2), and myocardial fibrosis measured by late gadolinium enhanced cardiac magnetic resonance imaging (LGE CMR) and their relation to left ventricular diastolic filling properties measured by tissue Doppler echocardiography (E/e') in patients with stable coronary artery disease (CAD).Methods and resultsWe determined the PINP, PIIINP, gal-3, and ST2 serum levels and performed LGE CMR and echocardiography on 63 patients with stable CAD without a history of prior myocardial infarction. Myocardial late gadolinium enhancement T1 relaxation time was defined as a specific marker of myocardial fibrosis. ST2, PINP, and PIIINP did not have a significant correlation with the post-LGE T1 relaxation time tertiles (NS for all), but the lowest post-LGE T1 relaxation time tertile had significantly higher gal-3 values than the other two tertiles (p = 0.002 and 0.002) and higher E/é-values (p = 0.009) compared to the highest T1 relaxation time tertile. ST2 (p = 0.025 and 0.029), gal-3 (p = 0.003 and < 0.001) and PIIINP (p = 0.001 and 0.007) levels were also significantly higher in the highest E/é tertile, compared to the other two tertiles.ConclusionsElevated serum levels of gal-3 reflect the degree of myocardial fibrosis assessed by LGE CMR. Gal-3, ST2, and PIIINP are also elevated in patients with impaired LV diastolic function, suggesting that these biomarkers are useful surrogates of structural and functional abnormality of the myocardium.

| S-EPMC4499700 | biostudies-literature

Serum Soluble ST2 and Adverse Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction.

Project description:Objective:To assess the dynamics of serum levels of soluble isoform of suppression of tumorigenicity 2 (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) and their correlations with the development of adverse left ventricular remodeling (LVR) through 6?months in patients with primary myocardial infarction with ST-segment elevation (STEMI). Methods:Subjects were 31 patients with STEMI (median age: 58?years), who underwent percutaneous coronary intervention (PCI) during the first 24?hours of the onset of myocardial infarction (MI). Blood samples and parameters of echocardiography were assessed at days 1, 3, 7, and 14 and 6?months after STEMI. Results:Serum levels of sST2 and NT-proBNP decreased during the 6-month period. Levels of sST2 decreased by 48% from admission to day 7, and levels of NT-proBNP decreased by 40% from day 7 to 6?months after STEMI. Serum levels of sST2 at day 1 (r?=?0.5, P?<?.05) and day 3 (r?=?0.4, P?<?.05) were associated with adverse LVR by 6?months after STEMI. Logistic regression analysis showed that a high concentration of sST2 at day 7 increased the risk of adverse LVR (95% confidence interval [CI], 0.5-0.9; areas under curve [AUC]?=?0.8; P?=?.002), with 92% sensitivity and 70% specificity. A multivariate analysis model revealed that adverse LVR was associated with the level of sST2 (P?=?.003) and with complete revascularization (P?=?.01) at the admission. Conclusions:The dynamics of serum levels of sST2 and NT-proBNP were different. The level of sST2 normalized by the 7th day; NT-proBNP decreased only by the end of the 6-month period after MI. Increased serum levels of sST2 by the 7th day of MI were associated with the development of adverse LVR by the end of the 6-month period.

| S-EPMC6487275 | biostudies-literature

Matrix metalloproteinase-9 deletion attenuates myocardial fibrosis and diastolic dysfunction in ageing mice.

Project description:AimsAge-related diastolic dysfunction has been attributed to an increased passive stiffness, which is regulated by extracellular matrix (ECM). We recently showed that matrix metalloproteinase (MMP)-9, an ECM mediator, increases in the left ventricle (LV) with age. The aim of this study, accordingly, was to determine the role of MMP-9 in cardiac ageing.Methods and resultsWe compared LV function in young (6-9 months), middle-aged (12-15 months), old (18-24 months) and senescent (26-34 months) wild-type (WT) and MMP-9 null mice (n ? 12/group). All groups had similar fractional shortenings and aortic peak velocities, indicating that systolic function was not altered by ageing or MMP-9 deletion. The mitral ratios of early to late diastolic filling velocities were reduced in old and senescent WT compared with young controls, and this reduction was attenuated in MMP-9 null mice. Concomitantly, the increase in LV collagen content was reduced in MMP-9 null mice (n = 5-6/group). To dissect the mechanisms of these changes, we evaluated the mRNA expression levels of 84 ECM and adhesion molecules by real-time qPCR (n = 6/group). The expression of pro-fibrotic periostin and connective tissue growth factor (CTGF) increased with senescence, as did transforming growth factor-? (TGF-?)-induced protein levels and Smad signalling, and these increases were blunted by MMP-9 deletion. In senescence, MMP-9 deletion also resulted in a compensatory increase in MMP-8.ConclusionMMP-9 deletion attenuates the age-related decline in diastolic function, in part by reducing TGF-? signalling-induced periostin and CTGF expression and increasing MMP-8 expression to regulate myocardial collagen turnover and deposition.

| S-EPMC3500048 | biostudies-literature

Association of Preterm Birth With Myocardial Fibrosis and Diastolic Dysfunction in Young Adulthood.

Project description:BackgroundPreterm birth affects about 10% of live births worldwide and is associated with cardiac alterations. Animal models of preterm birth suggest that left ventricular functional impairment may be due to an up-regulation of myocardial fibrosis.ObjectivesThe aim of this study was to determine whether diffuse left ventricular fibrosis is evident in young adults born preterm.MethodsOne hundred one normotensive young adults born preterm (n = 47, mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) were included from YACHT (Young Adult Cardiovascular Health sTudy). Left ventricular structure and function were quantified by cardiovascular magnetic resonance and echocardiography. Intravenous administration of a gadolinium-based contrast agent during cardiovascular magnetic resonance was used to quantify focal myocardial fibrosis on the basis of late gadolinium enhancement and, in combination with T1 mapping, to quantify diffuse myocardial fibrosis on the basis of assessment of myocardial extracellular volume fraction.ResultsAdults born preterm had smaller left ventricular end-diastolic and stroke volumes, with greater left ventricular mass and wall thickness (P < 0.001). In addition, longitudinal peak systolic strain and diastolic strain rate by both cardiovascular magnetic resonance and echocardiography, and E/A ratio measured by echocardiography, were lower in preterm-born compared to term-born adults (P < 0.05). Extracellular volume fraction was greater in preterm-born compared with term-born adults (27.81% ± 1.69% vs 25.48% ± 1.41%; P < 0.001) and was a significant mediator in the relationship between gestational age and both longitudinal peak diastolic strain rate and E/A ratio.ConclusionsPreterm-born young adults have greater extracellular volume fraction in the left ventricle that is inversely related with gestational age and may underlie their diastolic functional impairments.

| S-EPMC8363934 | biostudies-literature

Multiple common comorbidities produce left ventricular diastolic dysfunction associated with coronary microvascular dysfunction, oxidative stress, and myocardial stiffening.

Project description:Aims:More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance of diastolic dysfunction is higher in females and associates with multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), and diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these comorbidities induce systemic inflammation, coronary microvascular dysfunction, and oxidative stress, leading to myocardial fibrosis, myocyte stiffening and, ultimately, diastolic dysfunction. Here, we tested this hypothesis in a swine model chronically exposed to three common comorbidities. Methods and results:DM (induced by streptozotocin), HC (produced by high fat diet), and HT (resulting from renal artery embolization), were produced in 10 female swine, which were followed for 6?months. Eight female healthy swine on normal pig-chow served as controls. The DM?+?HC?+?HT group showed hyperglycemia, HC, hypertriglyceridemia, renal dysfunction and HT, which were associated with systemic inflammation. Myocardial superoxide production was markedly increased, due to increased NOX activity and eNOS uncoupling, and associated with reduced NO production, and impaired coronary small artery endothelium-dependent vasodilation. These abnormalities were accompanied by increased myocardial collagen content, reduced capillary/fiber ratio, and elevated passive cardiomyocyte stiffness, resulting in an increased left ventricular end-diastolic stiffness (measured by pressure-volume catheter) and a trend towards a reduced E/A ratio (measured by cardiac MRI), while ejection fraction was maintained. Conclusions:The combination of three common comorbidities leads to systemic inflammation, myocardial oxidative stress, and coronary microvascular dysfunction, which associate with myocardial stiffening and LV diastolic dysfunction with preserved ejection fraction.

| S-EPMC5967461 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data