Association of leukocyte telomere length with risk of all-cause and cardiovascular mortality in middle-aged and older individuals without cardiovascular disease: a prospective cohort study of NHANES 1999-2002.

BACKGROUND: Leukocyte telomere length (LTL) shorting was significantly associated with mortality. This study aimed to investigate the potential association between LTL and all-cause mortality as well as cardiovascular disease (CVD) mortality in middle-aged or older individuals without a history of CVD. METHODS: A total of 4174 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2002 were included in this analysis. Cox proportional hazards regression models were utilized to estimate the association between LTL and mortality outcomes. Restricted cubic spline (RCS) curves were employed to evaluate the potential non-linear association. RESULTS: Over a median follow-up period of 217 months, the weighted rates of all-cause mortality and CVD mortality were 28.58% and 8.32% respectively. Participants in the highest LTL group exhibited a significantly decreased risk of both all-cause mortality (HR: 0.65, 95% CI: 0.54-0.78, P < 0.001) and CVD mortality (HR: 0.64, 95% CI: 0.45-0.93, P < 0.001) compared to those in the lowest group. Kaplan-Meier survival curves further supported a significant association between shorter telomere length and increased risks of both all-cause and CVD mortality (log-rank test P < 0.001). RCS curves demonstrated a linear dose-response relationship between LTL and all-cause mortality as well as CVD mortality. Subgroup and sensitivity analyses confirmed the robustness of the results. CONCLUSION: Shorter leukocyte telomere length could serve as a potential biomarker for risk stratification of all-cause and CVD mortality among middle-aged and older individuals without a history of CVD.

Association between lipoprotein(a) and thromboembolism in patients with non-valvular atrial fibrillation: a cross-sectional study.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a recognized risk factor for ischemic stroke (IS); however, its role in thromboembolism in patients with non-valvular atrial fibrillation (NVAF) remains controversial. We aimed to assess the association of Lp(a) and IS and systemic embolism (SEE) in NVAF patients. METHODS: In total, 16,357 patients with NVAF were recruited from the First Affiliated Hospital of Xinjiang Medical University from January 1, 2009, to December 31, 2021, and were divided into groups based on Lp(a) quartiles. Logistic regression models analyzed the association between Lp(a), IS, and SEE. The restriction cubic spline was used to assess the potential nonlinear relationship between Lp(a), IS, and SEE. We conducted subgroup analyses and estimated the multiplicative interaction between the stratified variables and Lp(a) to investigate whether the association between Lp(a) and IS and SEE was affected by age, sex, anticoagulants, and CHA2DS2-VASc score. RESULTS: We identified 1319 IS and 133 SEE events. After correcting for CHA2DS2-VASc score and other potential confounders, each 1-standard deviation (SD) increase in log-Lp(a) was related to a 23% increased risk of IS (odds ratios [OR], 1.23; 95% confidence intervals [CI], 1.07-1.41). NVAF patients in the highest Lp(a) quartile were 1.23-fold more likely to have IS than those in the lowest quartile (OR, 1.23; 95% CI, 1.04-1.45). A positive linear relationship between Lp(a) and IS risk was observed (P for nonlinear = 0.341). In the fully adjusted model, subjects had a 1.78-fold increased risk of SEE for each 1-SD increase in log-Lp(a) (OR, 2.78; 95% CI, 1.78-4.36). Subjects in the highest Lp(a) quartile had a 2.38-fold elevated risk of SEE (OR, 3.38; 95% CI, 1.85-6.19) compared with the lowest quartile. Furthermore, Lp(a) had a nonlinear relationship with the risk of SEE (P for nonlinear = 0.005). CONCLUSIONS: Elevated Lp(a) concentration was significantly associated with IS and SEE, suggesting that Lp(a) may be an emerging biomarker that can help clinicians identify patients at high risk of thromboembolism in this population.

Predictive value of neutrophil-to-apolipoprotein A1 ratio in all-cause and cardiovascular death in elderly non-valvular atrial fibrillation patients.

Neutrophil-to-apolipoprotein AI ratio's (NAR's) predictive value for the elderly non-valvular atrial fibrillation (NVAF) patients' death has not been fully recognized. We consecutively enrolled 1224 elderly patients with NVAF (≥75 years). With an average follow-up of 733.35 ± 271.39 days, 222 all-cause deaths were identified. Among these, 101 were caused by cardiovascular diseases. Cox regression showed that after correcting for potential confounders, patients in the Q4 group had an increased all-cause (hazard ratio [HR] = 1.90, 95% confidence interval [CI]: 1.20-2.99) and cardiovascular death (HR = 2.59, 95% CI: 1.30-5.15) risk compared to those in the lowest NAR quartile. Kaplan-Meier analysis indicated that all-cause and cardiovascular death were higher in the high NAR than those in the lowest NAR category (log rank, all, P < 0.001). A nonlinear association was observed between death and NAR. NAR may be a promising predictive biomarker for identifying elderly NVAF patients with poor clinical prognoses.

A Review of Biomarkers for Ischemic Stroke Evaluation in Patients With Non-valvular Atrial Fibrillation.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide and results in a significantly increased ischemic stroke (IS) risk. IS risk stratification tools are widely being applied to guide anticoagulation treatment decisions and duration in patients with non-valvular AF (NVAF). The CHA2DS2-VASc score is largely validated and currently recommended by renowned guidelines. However, this score is heavily dependent on age, sex, and comorbidities, and exhibits only moderate predictive power. Finding effective and validated clinical biomarkers to assist in personalized IS risk evaluation has become one of the promising directions in the prevention and treatment of NVAF. A number of studies in recent years have explored differentially expressed biomarkers in NVAF patients with and without IS, and the potential role of various biomarkers for prediction or early diagnosis of IS in patients with NVAF. In this review, we describe the clinical application and utility of AF characteristics, cardiac imaging and electrocardiogram markers, arterial stiffness and atherosclerosis-related markers, circulating biomarkers, and novel genetic markers in IS diagnosis and management of patients with NVAF. We conclude that at present, there is no consensus understanding of a desirable biomarker for IS risk stratification in NVAF, and enrolling these biomarkers into extant models also remains challenging. Further prospective cohorts and trials are needed to integrate various clinical risk factors and biomarkers to optimize IS prediction in patients with NVAF. However, we believe that the growing insight into molecular mechanisms and in-depth understanding of existing and emerging biomarkers may further improve the IS risk identification and guide anticoagulation therapy in patients with NVAF.