@article {7671, title = {Association of biomarker and physiologic indices with mortality in older adults: Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, year = {2018}, month = {2018 Apr 12}, abstract = {

Background: A goal of gerontology is discovering aging phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers strongly and independently associated with mortality and which statistically attenuate chronologic age could be used to define such a phenotype. We determined the association of a Biomarker Index (BI) with mortality and compared it to a validated Physiologic Index (PI) in older adults.

Methods: The indices were constructed in the Cardiovascular Health Study, mean (SD) age 74.5 (5.1) years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor (IGF)-1, IGF binding protein 3, amino-terminal pro-B-type natriuretic peptide, dehydroepiandrosterone sulfate, and interleukin-6, and was built in test (N=2197) and validation (N=1124) samples. The PI included carotid intima-media thickness, pulmonary capacity, brain white matter grade, cystatin-C, and fasting glucose. Multivariable Cox proportional hazards models predicting death were calculated with 10 years of follow-up.

Results: In separate age-adjusted models, the hazard ratio (HR) for mortality per point of the BI was 1.30 (95\% CI 1.25, 1.34) and the BI attenuated age by 25\%. The HR for the PI was 1.28 (1.24, 1.33) (29\% age attenuation). In the same model, the HR for the BI was 1.23 (1.18, 1.28) and for the PI was 1.22 (1.17, 1.26), and age was attenuated 42.5\%. Associations persisted after further adjustment.

Conclusions: The BI and PI were significantly and independently associated with mortality. Both attenuated the age effect on mortality substantially. The indices may be feasible phenotypes for developing interventions hoping to alter the trajectory of aging.

}, issn = {1758-535X}, doi = {10.1093/gerona/gly075}, author = {Sanders, Jason L and Arnold, Alice M and Boudreau, Robert M and Hirsch, Calvin H and Kizer, Jorge R and Kaplan, Robert C and Cappola, Anne R and Cushman, Mary and Jacob, Mini E and Kritchevsky, Stephen B and Newman, Anne B} } @article {8790, title = {Association Between Myocardial Strain and Frailty in CHS.}, journal = {Circ Cardiovasc Imaging}, volume = {14}, year = {2021}, month = {2021 May}, pages = {e012116}, abstract = {

BACKGROUND: Myocardial strain, measured by speckle-tracking echocardiography, is a novel measure of subclinical cardiovascular disease and may reflect myocardial aging. We evaluated the association between myocardial strain and frailty-a clinical syndrome of lack of physiological reserve.

METHODS: Frailty was defined in participants of the CHS (Cardiovascular Health Study) as having >=3 of the following clinical criteria: weakness, slowness, weight loss, exhaustion, and inactivity. Using speckle-tracking echocardiography data, we examined the cross-sectional (n=3206) and longitudinal (n=1431) associations with frailty among participants who had at least 1 measure of myocardial strain, left ventricular longitudinal strain (LVLS), left ventricular early diastolic strain rate and left atrial reservoir strain, and no history of cardiovascular disease or heart failure at the time of echocardiography.

RESULTS: In cross-sectional analyses, lower (worse) LVLS was associated with prevalent frailty; this association was robust to adjustment for left ventricular ejection fraction (adjusted odds ratio, 1.32 [95\% CI, 1.07-1.61] per 1-SD lower strain; =0.007) and left ventricular stroke volume (adjusted OR, 1.32 [95\% CI, 1.08-1.61] per 1-SD lower strain; =0.007). In longitudinal analyses, adjusted associations of LVLS and left ventricular early diastolic strain with incident frailty were 1.35 ([95\% CI, 0.96-1.89] =0.086) and 1.58 ([95\% CI, 1.11-2.27] =0.013, respectively). Participants who were frail and had the worst LVLS had a 2.2-fold increased risk of death (hazard ratio, 2.20 [95\% CI, 1.81-2.66]; <0.0001).

CONCLUSIONS: In community-dwelling older adults without prevalent cardiovascular disease, worse LVLS by speckle-tracking echocardiography, reflective of subclinical myocardial dysfunction, was associated with frailty. Frailty and LVLS have an additive effect on mortality risk.

}, issn = {1942-0080}, doi = {10.1161/CIRCIMAGING.120.012116}, author = {Tan, Annabel X and Shah, Sanjiv J and Sanders, Jason L and Psaty, Bruce M and Wu, Chenkai and Gardin, Julius M and Peralta, Carmen A and Newman, Anne B and Odden, Michelle C} } @article {9114, title = {Association Between Preserved Ratio Impaired Spirometry and Clinical Outcomes in US Adults.}, journal = {JAMA}, volume = {326}, year = {2021}, month = {2021 12 14}, pages = {2287-2298}, abstract = {

Importance: Chronic lung diseases are a leading cause of morbidity and mortality. Unlike chronic obstructive pulmonary disease, clinical outcomes associated with proportional reductions in expiratory lung volumes without obstruction, otherwise known as preserved ratio impaired spirometry (PRISm), are poorly understood.

Objective: To examine the prevalence, correlates, and clinical outcomes associated with PRISm in US adults.

Design, Setting, and Participants: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study was a retrospective study with harmonized pooled data from 9 US general population-based cohorts (enrollment, 65 251 participants aged 18 to 102 years of whom 53 701 participants had valid baseline lung function) conducted from 1971-2011 (final follow-up, December 2018).

Exposures: Participants were categorized into mutually exclusive groups by baseline lung function. PRISm was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1:FVC) greater than or equal to 0.70 and FEV1 less than 80\% predicted; obstructive spirometry FEV1:FVC ratio of less than 0.70; and normal spirometry FEV1:FVC ratio greater than or equal to 0.7 and FEV1 greater than or equal to 80\% predicted.

Main Outcomes and Measures: Main outcomes were all-cause mortality, respiratory-related mortality, coronary heart disease (CHD)-related mortality, respiratory-related events (hospitalizations and mortality), and CHD-related events (hospitalizations and mortality) classified by adjudication or validated administrative criteria. Absolute risks were adjusted for age and smoking status. Poisson and Cox proportional hazards models comparing PRISm vs normal spirometry were adjusted for age, sex, race and ethnicity, education, body mass index, smoking status, cohort, and comorbidities.

Results: Among all participants (mean [SD] age, 53.2 [15.8] years, 56.4\% women, 48.5\% never-smokers), 4582 (8.5\%) had PRISm. The presence of PRISm relative to normal spirometry was significantly associated with obesity (prevalence, 48.3\% vs 31.4\%; prevalence ratio [PR], 1.68 [95\% CI, 1.55-1.82]), underweight (prevalence, 1.4\% vs 1.0\%; PR, 2.20 [95\% CI, 1.72-2.82]), female sex (prevalence, 60.3\% vs 59.0\%; PR, 1.07 [95\% CI, 1.01-1.13]), and current smoking (prevalence, 25.2\% vs 17.5\%; PR, 1.33 [95\% CI, 1.22-1.45]). PRISm, compared with normal spirometry, was significantly associated with greater all-cause mortality (29.6/1000 person-years vs 18.0/1000 person-years; difference, 11.6/1000 person-years [95\% CI, 10.0-13.1]; adjusted hazard ratio [HR], 1.50 [95\% CI, 1.42-1.59]), respiratory-related mortality (2.1/1000 person-years vs 1.0/1000 person-years; difference, 1.1/1000 person-years [95\% CI, 0.7-1.6]; adjusted HR, 1.95 [95\% CI, 1.54-2.48]), CHD-related mortality (5.4/1000 person-years vs 2.6/1000 person-years; difference, 2.7/1000 person-years [95\% CI, 2.1-3.4]; adjusted HR, 1.55 [95\% CI, 1.36-1.77]), respiratory-related events (12.2/1000 person-years vs 6.0/1000 person-years; difference, 6.2/1000 person-years [95\% CI, 4.9-7.5]; adjusted HR, 1.90 [95\% CI, 1.69-2.14]), and CHD-related events (11.7/1000 person-years vs 7.0/1000 person-years; difference, 4.7/1000 person-years [95\% CI, 3.7-5.8]; adjusted HR, 1.30 [95\% CI, 1.18-1.42]).

Conclusions and Relevance: In a large, population-based sample of US adults, baseline PRISm, compared with normal spirometry, was associated with a small but statistically significant increased risk for mortality and adverse cardiovascular and respiratory outcomes. Further research is needed to explore whether this association is causal.

}, keywords = {Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Female, Forced Expiratory Volume, Humans, Lung, Lung Diseases, Male, Middle Aged, Prevalence, Retrospective Studies, Spirometry, United States, Vital Capacity}, issn = {1538-3598}, doi = {10.1001/jama.2021.20939}, author = {Wan, Emily S and Balte, Pallavi and Schwartz, Joseph E and Bhatt, Surya P and Cassano, Patricia A and Couper, David and Daviglus, Martha L and Dransfield, Mark T and Gharib, Sina A and Jacobs, David R and Kalhan, Ravi and London, Stephanie J and Navas-Acien, Ana and O{\textquoteright}Connor, George T and Sanders, Jason L and Smith, Benjamin M and White, Wendy and Yende, Sachin and Oelsner, Elizabeth C} } @article {9438, title = {Association of a blood-based aging biomarker index with death and chronic disease: Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, year = {2023}, month = {2023 Jul 19}, abstract = {

BACKGROUND: A goal of gerontology is to discover phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that are strongly associated with mortality could be used to define such a phenotype. However, the relation of such an index with multiple chronic conditions warrants further exploration.

METHODS: A Biomarker Index (BI) was constructed in the Cardiovascular Health Study (N=3197), with a mean age of 74 years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, interleukin-6, amino-terminal pro-B-type natriuretic peptide, cystatin-C, C-reactive protein, tumor necrosis factor-alpha soluble receptor 1, fasting insulin, and fasting glucose, and was built based on their relationships with mortality. Cox proportional hazards models predicting a composite of death and chronic disease involving cardiovascular disease, dementia, and cancer were calculated with 6 years of follow-up.

RESULTS: The hazard ratio (HR, 95\% CI) for the composite outcome of death or chronic disease per category of BI was 1.65 (1.52, 1.80) and 1.75 (1.58, 1.94) in women and men, respectively. The HR (95\% CI) per 5 years of age was 1.57 (1.48, 1.67) and 1.55 (1.44, 1.67) in women and men, respectively. Moreover, BI could attenuate the effect of age on the composite outcome by 16.7\% and 22.0\% in women and men, respectively.

CONCLUSIONS: BI was significantly and independently associated with a composite outcome of death and chronic disease, and attenuated the effect of age. The BI that is composed of plasma biomarkers may be a practical intermediate phenotype for interventions aiming to modify the course of aging.

}, issn = {1758-535X}, doi = {10.1093/gerona/glad172}, author = {Zhang, Xiao and Sanders, Jason L and Boudreau, Robert M and Arnold, Alice M and Justice, Jamie N and Espeland, Mark A and Kuchel, George A and Barzilai, Nir and Kuller, Lewis H and Lopez, Oscar L and Kritchevsky, Stephen B and Newman, Anne B} }