Joint modeling of bivariate longitudinal and survival data in spouse pairs

We investigated the association between longitudinally measured depression scores and survival times simultaneously for paired spouse data from the Cardiovascular Health Study (CHS). We propose a joint model incorporating within pair correlations, both in the longitudinal and survival processes. We use bivariate linear mixed-effects models for the longitudinal processes, where the random effects are used to model the temporal correlation within each subject and the correlation across outcomes between subjects. For the survival processes, we incorporate gamma frailties into Weibull proportional hazards models to account for the correlation between survival times within pairs. The two sub-models are then linked through shared random effects, where the longitudinal and survival processes are conditionally independent given the random effects. Parameter estimates are obtained via the EM algorithm by maximizing the joint likelihood for the bivariate longitudinal and bivariate survival data. We use our method to model data where the use of bivariate longitudinal and survival sub–models are apropos but where there are no competing risks, that is, the censoring of one spouse’s time–to–mortality is not necessarily guaranteed by the death of the other spouse.

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Nonesterified Fatty Acids and Hospitalizations Among Older Adults: The Cardiovascular Health Study

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa228 ◽

2020 ◽

Author(s):

Peter D Ahiawodzi ◽

Petra Buzkova ◽

Luc Djousse ◽

Joachim H Ix ◽

Jorge R Kizer ◽

...

Keyword(s):

Older Adults ◽

Fatty Acids ◽

Cardiovascular Health ◽

Proportional Hazards ◽

Clinic Visit ◽

Cox Proportional Hazards ◽

Health Study ◽

Cardiovascular Health Study ◽

Total Serum ◽

Nonesterified Fatty Acids

Abstract Background We sought to determine associations between total serum concentrations of nonesterified fatty acids (NEFAs) and incident total and cause-specific hospitalizations in a community-living cohort of older adults. Methods We included 4715 participants in the Cardiovascular Health Study who had fasting total serum NEFA measured at the 1992/1993 clinic visit and were followed for a median of 12 years. We identified all inpatient admissions requiring at least an overnight hospitalization and used primary diagnostic codes to categorize cause-specific hospitalizations. We used Cox proportional hazards regression models to determine associations with time-to-first hospitalization and Poisson regression for the rate ratios (RRs) of hospitalizations and days hospitalized. Results We identified 21 339 hospitalizations during follow-up. In fully adjusted models, higher total NEFAs were significantly associated with higher risk of incident hospitalization (hazard ratio [HR] per SD [0.2 mEq/L] = 1.07, 95% confidence interval [CI] = 1.03–1.10, p < .001), number of hospitalizations (RR per SD = 1.04, 95% CI = 1.01–1.07, p = .01), and total number of days hospitalized (RR per SD = 1.06, 95% CI = 1.01–1.10, p = .01). Among hospitalization subtypes, higher NEFA was associated with higher likelihood of mental, neurologic, respiratory, and musculoskeletal causes of hospitalization. Among specific causes of hospitalization, higher NEFA was associated with diabetes, pneumonia, and gastrointestinal hemorrhage. Conclusions Higher fasting total serum NEFAs are associated with a broad array of causes of hospitalization among older adults. While some of these were expected, our results illustrate a possible utility of NEFAs as biomarkers for risk of hospitalization, and total days hospitalized, in older adults. Further research is needed to determine whether interventions based on NEFAs might be feasible.

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Silent Myocardial Infarction and Subsequent Ischemic Stroke in the Cardiovascular Health Study

Neurology ◽

10.1212/wnl.0000000000012249 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012249

Author(s):

Alexander E. Merkler ◽

Traci M. Bartz ◽

Hooman Kamel ◽

Elsayed Z. Soliman ◽

Virginia Howard ◽

...

Keyword(s):

Ischemic Stroke ◽

Cardiovascular Health ◽

Proportional Hazards ◽

Clinical Symptoms ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Health Study ◽

Cardiovascular Health Study ◽

Secondary Analyses ◽

New Evidence

Objective:To test the hypothesis that silent MI is a risk factor for ischemic stroke, we evaluated the association between silent MI and subsequent ischemic stroke in the Cardiovascular Health Study.Methods:The Cardiovascular Health Study prospectively enrolled community-dwelling individuals ≥65 years of age. We included participants without prevalent stroke or baseline evidence of MI. Our exposures were silent and clinically apparent, overt MI. Silent MI was defined as new evidence of Q-wave MI, without clinical symptoms of MI, on ECGs performed during annual study visits from 1989-1999. The primary outcome was incident ischemic stroke. Secondary outcomes were ischemic stroke subtypes: non-lacunar, lacunar, and other/unknown. Cox proportional hazards analysis was used to model the association between time-varying MI status (silent, overt, or no MI) and stroke after adjustment for baseline demographics and vascular risk factors.Results:Among 4,224 participants, 362 (8.6%) had an incident silent MI, 421 (10.0%) an incident overt MI, and 377 (8.9%) an incident ischemic stroke during a median follow-up of 9.8 years. After adjustment for demographics and comorbidities, silent MI was independently associated with subsequent ischemic stroke (HR, 1.51; 95% CI, 1.03-2.21). Overt MI was associated with ischemic stroke both in the short term (HR, 80; 95% CI, 53-119) and long term (HR, 1.60; 95% CI, 1.04-2.44). In secondary analyses, the association between silent MI and stroke was limited to non-lacunar ischemic stroke (HR 2.40; 95% CI, 1.36-4.22).Conclusion:In a community-based sample, we found an association between silent MI and ischemic stroke.

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Abstract 58: Silent Myocardial Infarction and Subsequent Ischemic Stroke in the Cardiovascular Health Study

Stroke ◽

10.1161/str.52.suppl_1.58 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Alexander E Merkler ◽

Traci Bartz ◽

Hooman Kamel ◽

Elsayed Z Soliman ◽

Virginia J Howard ◽

...

Keyword(s):

Myocardial Infarction ◽

Ischemic Stroke ◽

Cardiovascular Health ◽

Proportional Hazards ◽

Health Study ◽

Cardiovascular Health Study ◽

Short Term ◽

Silent Myocardial Infarction

Background: Whether silent myocardial infarction (MI) is a risk factor for ischemic stroke remains uncertain. Hypothesis: Silent MI is associated with incident ischemic stroke. Methods: The Cardiovascular Health Study prospectively enrolled community-dwelling individuals ≥65 years of age with follow-up through June 30, 2015. For this study, we included participants from the first study cohort (enrolled in 1989-1990) without prevalent stroke or baseline electrocardiographic (ECG) evidence of MI. Our exposures were silent and clinically apparent MI. Silent MI was defined as new evidence of Q-wave MI, without clinical symptoms of MI, on ECGs performed during annual study visits from 1989-1999. Clinically apparent (overt) MI was adjudicated on the basis of information about chest pain, ECG changes, and cardiac enzymes. The primary outcome was incident ischemic stroke. Secondary outcomes were ischemic stroke subtypes: non-lacunar, lacunar, and other/unknown. Cox proportional hazards analysis was used to model the association between time-varying MI status (silent, overt, or no MI) and stroke after adjustment for baseline demographics and vascular risk factors. Due to a violation of the proportional hazards assumption, the association between overt MI and stroke was modeled separately for short-term (within 30 days) and long-term (beyond 30 days) risk. Results: Among 4,224 participants included in this analysis, 362 (8.6%) had an incident silent MI, 421 (10.0%) an incident overt MI, and 377 (8.9%) an incident ischemic stroke during a median follow-up of 9.8 years. After adjustment for demographics and comorbidities, silent MI was independently associated with subsequent ischemic stroke (HR, 1.47; 95% CI, 1.01-2.16). Overt MI was associated with ischemic stroke both in the short term (HR, 80; 95% CI, 53-119) and long term (HR, 1.60; 95% CI, 1.04-2.44). In secondary analyses, the association between silent MI and stroke was limited to non-lacunar ischemic stroke (HR 2.18; 95% CI, 1.24-3.83). Conclusions: In a community-based sample, we found an association between silent MI and ischemic stroke, specifically non-lacunar stroke. These findings suggest that silent MI may be a novel risk factor for ischemic stroke.

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Abstract TP185: CRP as a Predictor for Hemorrhagic vs Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp185 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Stephanie Lyden ◽

Adam DeHavenon ◽

Vivek Reddy ◽

Jennifer Majersik

Keyword(s):

Ischemic Stroke ◽

Hemorrhagic Stroke ◽

Cardiovascular Health ◽

Proportional Hazards ◽

Elevated Serum ◽

Cox Proportional Hazards ◽

Health Study ◽

Secondary Outcome ◽

Cardiovascular Health Study ◽

Increased Risk

Background: Studies have found an association between elevated serum C reactive protein (CRP) levels and increased ischemic stroke risk 2,4-5 . Other studies have looked at whether CRP levels correlate with outcome and severity after ICH 1,3 . Less research has been done looking at CRP levels and the risk for hemorrhagic stroke. This study aims to confirm the association of baseline elevated serum CRP levels and increased risk for ischemic stroke, thus validating this dataset, and to evaluate whether these levels correlate with an increased risk for hemorrhagic stroke. Methods: This is a secondary analysis of the data from the Cardiovascular Health Study (CHS). The primary outcome is ischemic stroke and the secondary outcome is hemorrhagic stroke. The primary predictor is CRP level at baseline, as a continuous value and, after dividing into quintiles, a comparison between the lowest and highest quintiles. We fit Cox proportional hazards models and adjusted for baseline covariates that were associated with the outcomes, which for ischemic stroke included age, race, cholesterol, diabetes, hypertension, atrial fibrillation, and history of TIA or myocardial infarction; and for hemorrhagic stroke included age, cholesterol, diabetes, and hypertension. Results: We included 5,681 patients, of whom 918 (16.2%) had ischemic stroke and 150 (2.6%) had hemorrhagic stroke. Mean (SD) days of follow-up was 4,403 (2,504) and mean (SD) CRP was 4.8 (8.3). We found that baseline CRP was associated with ischemic stroke (HR 1.01, 95% CI 1.00-1.02, p=0.005), but not hemorrhagic stroke (HR 1.00, 95% CI 0.97-1.02, p=0.781). When comparing the highest to lowest quintile of CRP, we found a clinically significant increased risk of ischemic stroke (HR 1.37, 95% CI 1.11-1.70, p=0.004) (Figure 1), but again not for hemorrhagic stroke (p=0.852). Conclusion: Our analysis found that elevated baseline CRP levels are associated with an increased risk for ischemic stroke, but not hemorrhagic stroke.

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