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Plasma concentrations of molecular lipid species predict long-term clinical outcome in coronary artery disease patients.

ABSTRACT: We investigated the associations of ten previously identified high risk molecular lipid species and three ceramide ratios with the occurrence of major adverse cardiac events (MACEs) during a median follow-up of 4.7 years in patients with coronary artery disease (CAD). Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris (SAP) or acute coronary syndrome (ACS). Blood was drawn prior to the index procedure and lipid species were determined. The primary endpoint was the occurrence of a MACE, comprising all-cause mortality, nonfatal ACS, or unplanned coronary revascularization. The secondary endpoint comprised all-cause mortality or nonfatal ACS. During a median follow-up of 4.7 [IQR: 4.2-5.6] years, 155 patients (27%) had MACEs. In multivariable analyses, Cer(d18:1/16:0) concentration was associated with MACEs {hazard ratio 2.32; 95% CI [1.09-4.96] per natural logarithm (ln) (pmol/ml) P = 0.030} after adjustment for cardiac risk factors, clinical presentation, statin use at baseline, and admission nonHDL cholesterol level. Furthermore, after multivariable adjustment, concentrations of Cer(d18:1/16:0), Cer(d18:1/20:0), Cer(d18:1/24:1), and their ratios to Cer(d18:1/24:0) were associated with the composite endpoint death or nonfatal ACS. The data together show the circulating ceramide lipids we investigated here are associated with adverse cardiac outcome during long-term follow-up independent of clinical risk factors.

SUBMITTER: Anroedh S

PROVIDER: S-EPMC6121931 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults.

Project description:Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.Participants from the GLACIER Study (Nmax = 3492) were genotyped with the MetaboChip array, from which 29?387 SNPs (single nucleotide polymorphisms; replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (?TC) and triglycerides (?TG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; Nmax = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N ? 190?000) and functional annotation for the top ranking variants.In total, 956 variants were associated (P < 0.01) with either ?TC or ?TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with ?TG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5?×?10-8), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 × 10-6). The rs7412 variant at APOE was associated with ?TC in GLACIER (P < 1.7 × 10-6). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with ?TC and for ?TG, respectively (P < 10-3). Of these, a variant at CAPN3 (P = 1.2 × 10-4), multiple variants at HPR (Pmin = 1.5 × 10-6) and a variant at SIX5 (P = 1.9 × 10-4) showed evidence for association with CAD.We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.

| S-EPMC5837581 | biostudies-literature

Circulating Chemerin Levels, but not the RARRES2 Polymorphisms, Predict the Long-Term Outcome of Angiographically Confirmed Coronary Artery Disease.

Project description:Chemerin, a novel adipokine, has been associated with metabolic, inflammatory, and atherosclerotic diseases. We aimed to determine the genetic basis of chemerin levels by conducting a genome-wide association study (GWAS) and to investigate the role of RARRES2 polymorphisms and circulating chemerin levels in the long-term outcome of coronary artery disease (CAD). A total of 2197 participants from the Taiwan Biobank (TWB) were recruited for the GWAS analysis, and 481 patients with angiographically confirmed CAD were enrolled for long-term outcome analysis. One locus of genome-wide significance with a single independent association signal was identified in the GWAS for chemerin levels with the peak association at the RARRES2 gene promoter region polymorphism rs3735167 (p = 2.35 × 10-21). In the CAD population, borderline significance was noted between RARRES2 polymorphisms and chemerin levels, whereas high chemerin levels were associated with obesity, female sex, diabetes mellitus, hypertension, current smoking, high platelet and leukocyte counts, anemia, impaired renal function, high C-reactive protein (CRP) levels, and multi-vessel disease. Kaplan?Meier survival curves indicated that the patients with high chemerin and CRP levels, but not those with RARRES2 polymorphisms, had a lower survival rate and higher combined cerebral and cardiovascular event rates. Combined chemerin and CRP levels further revealed a stepwise increase in poor clinical outcomes from low- to high-risk subgroups. In conclusion, rs3735167 is the lead RARRES2 polymorphism for chemerin levels in Taiwanese. Chemerin levels, but not the rs3735167 genotypes, predicted the long-term outcome of CAD, especially when combined with CRP levels.

| S-EPMC6429458 | biostudies-literature

Correction: Plasma Concentrations Predict Aortic Expression of Growth-Arrest-Specific Protein 6 in Patients Undergoing Coronary Artery Bypass Grafting.

Project description:[This corrects the article DOI: 10.1371/journal.pone.0079452.].

| S-EPMC5402953 | biostudies-literature

Plasma procalcitonin concentrations predict organ dysfunction and outcome in dogs with sepsis.

Project description:BackgroundProcalcitonin (PCT) is a valuable prognostic biomarker in human sepsis that is predictive of organ dysfunction, septic shock and mortality. Data on PCT in dogs is limited. This study aimed to investigate the prognostic value of baseline and serial PCT measurements in dogs with sepsis and to determine the association between PCT and sepsis severity and the presence of organ dysfunction. PCT concentrations were measured in citrated plasma samples collected from 53 dogs with sepsis at the time of admission (T0, n?=?53) and at 24 h (T1, n?=?35) and 48 h (T2, n?=?30) post-admission using a commercial ELISA. Dogs were classified by sepsis severity (sepsis without organ dysfunction; severe sepsis; septic shock) and outcome (survivors; non-survivors). Organ dysfunctions were recorded at T0 and during hospitalization, and the APPLEfast score calculated at T0. Healthy dogs (n?=?12) were used as controls.ResultsThere were 18 septic dogs without organ dysfunction, 24 dogs with severe sepsis and 11 with septic shock. Baseline PCT concentrations were significantly greater in dogs with sepsis compared to healthy controls (P?<?0.0001), and in dogs with septic shock compared to dogs without cardiovascular compromise (P?=?0.01). Baseline PCT was significantly correlated with organ dysfunction (P?=?0.003). Declining PCT concentrations were documented in survivors at T1 and T2 compared to PCT at T0 (P?=?0.0006), and PCT clearance at 24 h was significantly higher in survivors (n?=?38) compared to non-survivors (n?=?15) (P?=?0.037). Canine APPLEfast score was not predictive of sepsis severity, the development of MODS or outcome.ConclusionIn dogs with sepsis, PCT concentrations at hospital admissions are predictive of organ dysfunction and septic shock. Serial procalcitonin monitoring may offer valuable prognostic information in canine sepsis, wherein early decreases in PCT concentrations are associated with survival.

| S-EPMC5870177 | biostudies-literature

Impact of clinical presentation and presence of coronary sclerosis on long-term outcome of patients with non-obstructive coronary artery disease.

Project description:BACKGROUND:Non-obstructive coronary artery disease (NOCAD) is a common finding on coronary angiography. Our goal was to evaluate the long-term prognosis of NOCAD patients with stable angina (SA). METHODS:The study cohort consisted of 7478 NOCAD patients with normal EF (? 50%), and SA who underwent coronary angiography between 1995 and 2012. We compared NOCAD patients (stenosis<?50%) with 10,906 patients with stable obstructive CAD (? 50%). The primary endpoint was all-cause mortality. Secondary endpoints included repeat angiography, progressive CAD, and PCI. A second comparison group consisted of 7344 patients with NOCAD presenting with an ACS. Rates of all-cause mortality of NOCAD ACS patients were compared to NOCAD SA patients. RESULTS:Median follow-up time was 6.5 years. NOCAD patients had a lower risk of all-cause mortality compared to CAD patients (HR CAD vs. NOCAD 1.33 (1.19-1.49); p?<?0.001). This was driven by patients with normal coronary arteries (HR CAD vs. normal 1.63 (1.36-1.94), p?<?0.001), whereas patients with minimal disease (>?0% and?<?50%) were at similar risk as CAD patients (HR CAD vs. minimal 1.08 (0.99-1.29), p?=?0.06). In NOCAD patients, the strongest predictors of all-cause mortality were age and minimal disease. SA patients with NOCAD had low rates of repeat angiography (7.3%), future CAD (2.3%) and PCI (1.7%). NOCAD ACS patients had a 41% increase in all-cause mortality risk compared to NOCAD SA patients (HR 1.41 (1.25-1.6), p?<?0.001). CONCLUSIONS:This study underlines the importance of minimal CAD, as it is not a benign disease entity and portends a similar risk as stable obstructive CAD.

| S-EPMC6106760 | biostudies-literature

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery.

Project description:Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n = 960). AKI was defined as a ? 50% or ? 0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P = 0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.

| S-EPMC4657830 | biostudies-literature

Newly identified loci that influence lipid concentrations and risk of coronary artery disease.

Project description:To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.

| S-EPMC5206900 | biostudies-literature

Sex-specific differences and long-term outcome of patients with coronary artery disease and chronic kidney disease: the Coronary Artery Disease and Renal Failure (CAD-REF) Registry.

Project description:BackgroundCardiovascular morbidity and mortality are closely linked to chronic kidney disease (CKD). Sex-specific long-term outcome data of patients with coronary artery disease (CAD) and CKD are scarce.MethodsIn the prospective observational multicenter Coronary Artery Disease and REnal Failure (CAD-REF) Registry, 773 (23.1%) women and 2,579 (76.9%) men with angiographically documented CAD and different stages of CKD were consecutively enrolled and followed for up to 8 years. Long-term outcome was evaluated using survival analysis and multivariable Cox-regression models.ResultsAt enrollment, women were significantly older than men, and suffered from more comorbidities like CKD, hypertension, diabetes mellitus, and multivessel coronary disease. Regarding long-term mortality, no sex-specific differences were observed (Kaplan-Meier survival estimates: 69% in women vs. 69% in men, plog-rank = 0.7). Survival rates decreased from 89% for patients without CKD at enrollment to 72% for patients with CKD stages 1-2 at enrollment and 49% for patients with CKD stages 3-5 at enrollment (plog-rank < 0.001). Cox-regression analysis revealed that sex or multivessel coronary disease were no independent predictors of long-term mortality, while age, CKD stages 3-5, albumin/creatinine ratio, diabetes, valvular heart disease, peripheral artery disease, and left-ventricular ejection fraction were predictors of long-term mortality.ConclusionsSex differences in CAD patients mainly exist in the cardiovascular risk profile and the extent of CAD. Long-term mortality was not depended on sex or multivessel disease. More attention should be given to treatment of comorbidities such as CKD and peripheral artery disease being independent predictors of death. Clinical Trail Registration ClinicalTrials.gov Identifier: NCT00679419.

| S-EPMC8484247 | biostudies-literature

Relations of long-term and contemporary lipid levels and lipid genetic risk scores with coronary artery calcium in the framingham heart study.

Project description:OBJECTIVES:This study evaluated the association of timing of lipid levels and lipid genetic risk score (GRS) with subclinical atherosclerosis. BACKGROUND:Atherosclerosis is a slowly progressive disorder influenced by suboptimal lipid levels. Long-term versus contemporary lipid levels may more strongly impact the development of coronary artery calcium (CAC). METHODS:Framingham Heart Study (FHS) Offspring Cohort participants (n = 1,156, 44% male, 63 ± 9 years) underwent serial fasting lipids (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein, and triglycerides), Exam 1 (1971 to 1975) to Exam 7 (1998 to 2001). FHS Third Generation Cohort participants (n = 1,954, 55% male, 45 ± 6 years) had fasting lipid profiles assessed, 2002 to 2005. Computed tomography (2002 to 2005) measured CAC. Lipid GRSs were computed from significantly associated single-nucleotide polymorphisms. The association between early, long-term average, and contemporary lipids, and lipid GRS with elevated CAC was assessed using logistic regression. RESULTS:In FHS Offspring, Exam 1 and long-term average as compared with Exam 7 lipid measurements, including untreated lipid levels, were strongly associated with elevated CAC. In the FHS Third Generation, contemporary lipids were associated with CAC. The LDL-C GRS was associated with CAC (age-/sex-adjusted odds ratio: 1.14, 95% confidence interval: 1.00 to 1.29, p = 0.04). However, addition of the GRS to the lipid models did not result in a significant increase in the odds ratio or C-statistic for any lipid measure. CONCLUSIONS:Early and long-term average lipid levels, as compared with contemporary measures, are more strongly associated with elevated CAC. Lipid GRS was associated with lipid levels but did not predict elevated CAC. Adult early and long-term average lipid levels provide important information when assessing subclinical atherosclerosis and cardiovascular risk.

| S-EPMC3702262 | biostudies-literature

Impact of patients´ age on short and long-term outcome after carotid endarterectomy and simultaneous coronary artery bypass grafting.

Project description:BACKGROUND:The purpose of this study was to investigate whether age has an effect on short and long-term outcome in patients who undergo simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy. METHODS:From 2005 to 2017, 186 consecutive elective patients underwent CABG and synchronous endarterectomy at our institution. Patients were retrospectively classified according to age into 2 groups: patients above 70 years (elderly group: n = 97, 76.1 ± 3.9 years) and patients below 70 years (younger group: n = 89, 63.2 ± 4.8 years). RESULTS:The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, 4.4% vs. 2.5%; p < 0.001) and Society of Thoracic Surgeons (STS) score (0.7% vs. 1.6%; p < 0.001) were significantly higher in the elderly group. Otherwise, there was no difference between the two groups concerning important preoperative risk factors or the intraoperative data. Postoperatively, the incidence of temporary dialysis was significantly higher in the elderly group (14.4% vs. 3.4%; p = 0.009). The rate of tracheotomy (16.5% vs. 2.2%; p = 0.001), of re-intubation (7.9% vs. 18.6%; p = 0.033) and drainage loss (600 ml vs. 800 ml; p = 0.035) was significantly higher in this elderly group. Neurological complications and 30-day mortality were comparable. Long-term survival was satisfactory for both groups. Nevertheless, 5-year survival rates (63% vs. 85%) were significantly lower in the elderly group (p = 0.003). Logistic regression analysis identified chronic obstructive pulmonary disease (COPD) and arrhythmia as significant risk factors for 30-day-mortality, but not age. CONCLUSIONS:CABG in combination with synchronous endarterectomy can also be performed with satisfactory results in elderly patients.

| S-EPMC6570883 | biostudies-other

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