@article {771, title = {Congestive heart failure in the elderly: the Cardiovascular Health Study.}, journal = {Am J Geriatr Cardiol}, volume = {13}, year = {2004}, month = {2004 Mar-Apr}, pages = {61-8}, abstract = {

Congestive heart failure in the elderly is recognized as a national public health priority; however, clinical diagnosis can be problematic in elderly persons, many of whom have a history of heart failure in the presence of normal or only minimally decreased ejection fraction. Findings of the Cardiovascular Health Study have underscored the common substrate and predictors underlying heart failure both with decreased ejection fraction and with normal ejection fraction (i.e., diastolic heart failure). Coronary heart disease, systolic blood pressure, and C-reactive protein (a measure of inflammation) are predictive of heart failure independent of ejection fraction. Left atrial size, arguably a marker of the effects of impaired diastolic filling over time, is increased in both systolic and diastolic heart failure of the elderly, as is atrial natriuretic peptide. The outcome of heart failure in elderly persons is poor both for systolic and diastolic heart failure. Moreover, many community-dwelling elderly persons have decreased ejection fraction without heart failure. In these persons the chance of death is similar to that of participants with diastolic heart failure. Since most clinical trials have studied younger patients with predominantly systolic heart failure, the appropriate therapy for heart failure in elderly persons remains to be determined.

}, keywords = {Aged, Aged, 80 and over, Atrial Natriuretic Factor, Blood Pressure, Diagnosis, Differential, Female, Geriatric Assessment, Heart Atria, Heart Failure, Heart Rate, Humans, Incidence, Male, Prevalence, Risk Factors, Stroke Volume, United States, Ventricular Dysfunction, Left}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2004.02121.x}, author = {Mathew, Sunil T and Gottdiener, John S and Kitzman, Dalane and Aurigemma, Gerard} } @article {1136, title = {Left atrial volume and geometry in healthy aging: the Cardiovascular Health Study.}, journal = {Circ Cardiovasc Imaging}, volume = {2}, year = {2009}, month = {2009 Jul}, pages = {282-9}, abstract = {

BACKGROUND: The left atrium is a validated marker of clinical and subclinical cardiovascular disease. Left atrial enlargement is often seen among older individuals; however, there are few population-based data regarding normal left atrial size among older persons, especially from those who are healthy, and from women. Furthermore, because the left atrium is a 3D structure, the commonly used parasternal long-axis diastolic diameter often underdiagnoses left atrial enlargement.

METHODS AND RESULTS: We evaluated left atrial size in 230 healthy participants (mean age, 76+/-5 years) free of prevalent cardiac disease, rhythm abnormality, hypertension, and diabetes selected from the Cardiovascular Health Study, a prospective community-based study of risk factors for cardiovascular disease in 5888 elderly participants. In addition to the standard long-axis measurement, we obtained left atrial superoinferior and lateral diameters and used these dimensions to estimate left atrial volume. These measurements were used to generate reference ranges for determining left atrial enlargement in older men and women, based on the 95\% percentiles of the left atrial dimensions in healthy participants, both unadjusted, and after adjustment for age, height, and weight. In healthy elderly subjects, indices of left atrial size do not correlate with age or height but with weight and other measures of body build.

CONCLUSIONS: These data provide normative reference values for left atrial size in healthy older women and men. The results should be useful for refining diagnostic criteria for left atrial dilation in the older population and may be relevant for cardiovascular risk stratification.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Atrial Function, Left, Body Size, Body Surface Area, Echocardiography, Three-Dimensional, Female, Heart Atria, Humans, Linear Models, Male, Models, Biological, Organ Size, Population Surveillance, Prospective Studies, Reference Values, Sex Factors, United States}, issn = {1942-0080}, doi = {10.1161/CIRCIMAGING.108.826602}, author = {Aurigemma, Gerard P and Gottdiener, John S and Arnold, Alice M and Chinali, Marcello and Hill, Jeffrey C and Kitzman, Dalane} } @article {1196, title = {Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies.}, journal = {Am Heart J}, volume = {159}, year = {2010}, month = {2010 May}, pages = {864-70}, abstract = {

BACKGROUND: Many African Americans carry an amyloidogenic transthyretin mutation (TTR V122I), with a high risk for cardiac TTR amyloid deposition after the age of 65 years. We wished to determine the allele frequency and its clinical penetrance in community-dwelling African Americans.

METHODS: Five thousand consenting African Americans, aged 41 to 93 years, in 2 community studies of cardiovascular risk (CHS and ARIC) were included in the study. The following were performed: genotyping of banked DNA for TTR V122I allele status and review of cardiovascular and demographic parameters in CHS and ARIC databases, with statistical comparisons of the frequency of congestive heart failure, survival, and occurrence of features of cardiac amyloidosis in carriers of the amyloidogenic allele and controls.

RESULTS: One hundred nineteen (3.23\%) of 3,712 ARIC and 17 (2.12\%) of 805 CHS African Americans carried TTR V122I. After the age of 65 years (CHS), the frequencies of congestive heart failure (38\% vs 15\%, relative risk 2.62, P = .04) and mortality (76\% vs 53\%, relative risk 1.46, P = .08) were higher in V122I allele carriers than in age-, gender- and ethnically matched controls. In ARIC (all subjects <65 years old), there were no differences between carriers and noncarriers in mortality, frequency of congestive heart failure, or findings consistent with cardiac amyloidosis.

CONCLUSIONS: Heterozygosity for the amyloidogenic TTR V122I mutation is relatively common in community-dwelling African Americans. Before the age of 65 years, the allele has no discernible impact on cardiac function or mortality. After the age of 70 years, carriers show a higher frequency of congestive failure and greater mortality with more echocardiographic evidence suggestive of cardiac amyloidosis, findings consistent with age-dependent clinical penetrance of this autosomal dominant gene.

}, keywords = {Adult, African Americans, Aged, Aged, 80 and over, Amyloidosis, Female, Gene Frequency, Heart Diseases, Humans, Isoleucine, Kaplan-Meier Estimate, Male, Middle Aged, Mutation, Prealbumin, Ultrasonography, Valine}, issn = {1097-6744}, doi = {10.1016/j.ahj.2010.02.006}, author = {Buxbaum, Joel and Alexander, Alice and Koziol, James and Tagoe, Clement and Fox, Ervin and Kitzman, Dalane} } @article {9705, title = {High Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life.}, journal = {JAMA Cardiol}, volume = {9}, year = {2024}, month = {2024 Jul 01}, pages = {649-658}, abstract = {

IMPORTANCE: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions.

OBJECTIVE: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023.

EXPOSURES: Protein aptamers, measured at study V3 and V5.

MAIN OUTCOMES AND MEASURES: Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty.

RESULTS: A total of 4877 protein aptamers were measured among 10 638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46\%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 {\texttimes} 10-5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 {\texttimes} 10-4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42\%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 {\texttimes} 10-4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 {\texttimes} 10-3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF.

CONCLUSIONS AND RELEVANCE: In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.

}, keywords = {Aged, Biomarkers, Female, Frailty, Heart Failure, Humans, Incidence, Male, Middle Aged, Proteomics, Risk Factors}, issn = {2380-6591}, doi = {10.1001/jamacardio.2024.1178}, author = {Ramonfaur, Diego and Buckley, Leo F and Arthur, Victoria and Yang, Yimin and Claggett, Brian L and Ndumele, Chiadi E and Walker, Keenan A and Austin, Thomas and Odden, Michelle C and Floyd, James S and Sanders-van Wijk, Sandra and Njoroge, Joyce and Kizer, Jorge R and Kitzman, Dalane and Konety, Suma H and Schrack, Jennifer and Liu, Fangyu and Windham, B Gwen and Palta, Priya and Coresh, Josef and Yu, Bing and Shah, Amil M} }