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The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome.

ABSTRACT: BACKGROUND:Non-ST elevation acute coronary syndrome (NSTEACS) occurs more frequently in older patients with an increased occurrence of recurrent cardiac events following the index presentation. Telomeres are structures consisting of repeated DNA sequences as associated shelterin proteins at the ends of chromosomes. We aim to determine whether telomere length (TL) and telomerase activity (TA) predicted poor outcomes in older patients presenting with NSTEACS undergoing invasive care. METHOD:Older patients undergoing invasive management for NSTEACS were recruited to the ICON-1 biomarker study (NCT01933581). Peripheral blood mononuclear cells (PBMC) were recovered on 153 patients. DNA was isolated and mean TL was measured by quantitative PCR expressed as relative T (telomere repeat copy number) to S (single copy gene number) ratio (T/S ratio), and a telomere repeat amplification assay was used to assess TA during index presentation with NSTEACS. Primary clinical outcomes consisted of death, myocardial infarction (MI), unplanned revascularisation, stroke and significant bleeding recorded at 1 year. TL and TA were divided into tertile groups for analysis. Cox proportional hazards regression was performed. Ordinal regression was performed to evaluate the relationship between TL and TA and traditional cardiovascular risk factors at baseline. RESULTS:298 patients were recruited in the ICON-1 study of which 153 had PBMC recovered. The mean age was 81.0 ± 4.0 years (64% male). Mean telomere length T/S ratio was 0.47 ± 0.25 and mean TA was 1.52 ± 0.61 units. The primary composite outcome occurred in 44 (28.8%) patients. There was no association between short TL or low TA and incidence of the primary composite outcome (Hazard Ratio [HR] 1.50, 95% Confidence Interval [CI] 0.68-3.34, p = 0.32 and HR 1.33, 95% CI 0.52-3.36, p = 0.51 respectively). CONCLUSION:TL and TA are not found to be associated with the incidence of adverse outcomes in older patients presenting with NSTEACS undergoing invasive care. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov Unique identifier: NCT01933581.

SUBMITTER: Chan D

PROVIDER: S-EPMC6953865 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome.

Chan Danny D Martin-Ruiz Carmen C Saretzki Gabriele G Neely Dermot D Qiu Weiliang W Kunadian Vijay V

PloS one 20200110 1

<h4>Background</h4>Non-ST elevation acute coronary syndrome (NSTEACS) occurs more frequently in older patients with an increased occurrence of recurrent cardiac events following the index presentation. Telomeres are structures consisting of repeated DNA sequences as associated shelterin proteins at the ends of chromosomes. We aim to determine whether telomere length (TL) and telomerase activity (TA) predicted poor outcomes in older patients presenting with NSTEACS undergoing invasive care.<h4>Me ...[more]

PMID: 31923255

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Project description:OBJECTIVE: To investigate comorbid conditions with prognostic influence in non-ST-segment elevation acute coronary syndrome (NSTEACS). PATIENTS AND METHODS: The study group consisted of a derivation cohort of 1017 patients (admitted from October 1, 2002, through October 1, 2008) and an external validation cohort of 652 patients (admitted from February 1, 2006, through September 30, 2009). Comorbid conditions, including risk factors and components of the Charlson comorbidity index (ChCI) and coronary artery disease-specific index, were recorded. The main outcome was one-year mortality. RESULTS: During follow-up, 103 patients died. After adjusting for variables associated with NSTEACS characteristics (base model), 5 comorbid conditions predicted mortality: severe or mild renal failure (hazard ratio [HR], 2.9 and HR, 1.6, respectively), dementia (HR, 3.1), peripheral artery disease (HR, 2.0), previous heart failure (HR, 2.6), and previous myocardial infarction (HR, 1.4). A simple comorbidity index (SCI) was developed using these variables, (per point: HR, 1.6; 95% confidence interval, 1.4-1.8; P = .0001). Adding the SCI, Charlson comorbidity index, or coronary artery disease-specific index to the base model resulted in a gain of 6.58%, 5.00%, and 4.04%, respectively, in discriminative ability (P = .001), without significant differences among the 3 indices. In patients with comorbid conditions, the highest risk period was in the first weeks after NSTEACS. The strength of the association between SCI and mortality rate was similar in the external validation cohort (HR, 1.3; 95% confidence interval, 1.1-1.6; P = .001). CONCLUSION: Renal dysfunction, dementia, peripheral artery disease, previous heart failure, and previous myocardial infarction are the comorbid conditions that predict mortality in NSTEACS. A simple index using these variables proved to be as accurate as the more complex comorbidity indices for risk stratification. In-hospital management of patients with comorbid conditions merits further investigation.

Project description:Objective:We aim to evaluate the long-term prognosis of non-ST elevation acute coronary syndrome (NSTE-ACS) patients with high-risk coronary anatomy (HRCA). Background:Coronary disease severity is important for therapeutic decision-making and prognostication among patients presenting with NSTE-ACS. However, long-term outcome in patients undergoing percutaneous coronary intervention (PCI) with HRCA is still unknown. Method:NSTE-ACS patients undergoing PCI in Fuwai Hospital in 2013 were prospectively enrolled and subsequently divided into HRCA and low-risk coronary anatomy (LRCA) groups according to whether angiography complies with the HRCA definition. HRCA was defined as left main disease >50%, proximal LAD lesion >70%, or 2- to 3- vessel disease involving the LAD. Prognosis impact on 2-year and 5-year major adverse cardiovascular and cerebrovascular events (MACCE) is analyzed. Results:Out of 4,984 enrolled patients with NSTE-ACS, 3,752 patients belonged to the HRCA group, while 1,232 patients belonged to the LRCA group. Compared with the LRCA group, patients in the HRCA group had worse baseline characteristics including higher age, more comorbidities, and worse angiographic findings. Patients in the HRCA group had higher incidence of unplanned revascularization (2 years: 9.7% vs. 5.1%, p < 0.001; 5 years: 15.4% vs. 10.3%, p < 0.001), 2-year MACCE (13.1% vs. 8.8%, p < 0.001), and 5-year death/MI/revascularization/stroke (23.0% vs. 18.4%, p = 0.001). Kaplan-Meier survival analysis showed similar results. After adjusting for confounding factors, HRCA is independently associated with higher risk of revascularization (2 years: HR?=?1.636, 95% CI: 1.225-2.186; 5 years: HR?=?1.460, 95% CI: 1.186-1.798), 2-year MACCE (HR?=?1.275, 95% CI?=?1.019-1.596) and 5-year death/MI/revascularization/stroke (HR?=?1.183, 95% CI: 1.010-1.385). Conclusion:In our large cohort of Chinese patients, HRCA is an independent risk factor for long-term unplanned revascularization and MACCE.

Dataset Information

The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome.

Publications

The association of telomere length and telomerase activity with adverse outcomes in older patients with non-ST-elevation acute coronary syndrome.

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