Cardiovascular damage phenotypes and all-cause and CVD mortality in older adults

Lindsay M. Miller, Chenkai Wu, Calvin H. Hirsch, Oscar L. Lopez, Mary Cushman, Michelle C. Odden

Research output: Contribution to journalArticlepeer-review


Purpose: The association between CVD risk factors and mortality is well established, however, current tools for addressing subgroups have focused on the overall burden of disease. The identification of risky combinations of characteristics may lead to a better understanding of physiologic pathways that underlie morbidity and mortality in older adults. Methods: Participants included 5067 older adults from the Cardiovascular Health Study, followed for up to 6 years. Using latent class analysis (LCA), we created CV damage phenotypes based on probabilities of abnormal brain infarctions, major echocardiogram abnormalities, N-terminal probrain natriuretic peptide, troponin T, interleukin-6, c reactive-protein, galectin-3, cystatin C. We assigned class descriptions based on the probability of having an abnormality among risk factors, such that a healthy phenotype would have low probabilities in all risk factors. Participants were assigned to phenotypes based on the maximum probability of membership. We used Cox-proportional hazards regression to evaluate the association between the categorical CV damage phenotype and all-cause and CVD-mortality. Results: The analysis yielded 5 CV damage phenotypes consistent with the following descriptions: healthy (59%), cardio-renal (11%), cardiac (15%), multisystem morbidity (6%), and inflammatory (9%). All four phenotypes were statistically associated with a greater risk of all-cause mortality when compared with the healthy phenotype. The multisystem morbidity phenotype had the greatest risk of all-cause death (HR: 4.02; 95% CI: 3.44, 4.70), and CVD-mortality (HR: 4.90, 95% CI: 3.95, 6.06). Conclusions: Five CV damage phenotypes emerged from CVD risk factor measures. CV damage across multiple systems confers a greater mortality risk compared to damage in any single domain.

Original languageEnglish (US)
Pages (from-to)35-40
Number of pages6
JournalAnnals of Epidemiology
StatePublished - Nov 2021
Externally publishedYes


  • AAI, ankle arm index
  • ADL, Activities of Daily Living
  • AIC, Akaike Information Criterion
  • APOE, Apolipoprotein e4
  • BIC, Bayesian Information Criterion
  • CHS, Cardiovascular Health Study
  • CRP, C-reactive protein
  • ECG, major echocardiogram abnormalities
  • Gal3, galectin-3
  • GOF, Goodness of Fit
  • HR, Hazard Ratio
  • IL-6, interleukin-6
  • IMT, internal intima-media thickness
  • LCA, Latent Class Analysis
  • LDLcholesterol, Low-density Lipoprotein Cholesterol
  • NTproBNP, N-terminal probrain natriuretic peptide
  • Risk factors, Cardiovascular disease, Latent Class Analysis. Abbreviations: CVD, Cardiovascular Disease
  • SCVD, Subclinical Cardiovascular Disease
  • WMG, white matter grade

ASJC Scopus subject areas

  • Epidemiology


Dive into the research topics of 'Cardiovascular damage phenotypes and all-cause and CVD mortality in older adults'. Together they form a unique fingerprint.

Cite this