scholarly journals Maladaptive Changes Associated With Cardiac Aging Are Sex-Specific and Graded by Frailty and Inflammation in C57BL/6 Mice

Author(s):  
Alice E Kane ◽  
Elise S Bisset ◽  
Stefan Heinze-Milne ◽  
Kaitlyn M Keller ◽  
Scott A Grandy ◽  
...  

Abstract We investigated whether late-life changes in cardiac structure and function were related to high levels of frailty and inflammation in male and female mice. Frailty (frailty index), ventricular structure/function (echocardiography), and serum cytokines (multiplex immunoassay) were measured in 16- and 23-month-old mice. Left ventricular (LV) mass and septal wall thickness increased with age in both sexes. Ejection fraction increased with age in males (60.4 ± 1.4 vs 68.9 ± 1.8%; p < .05) but not females (58.8 ± 2.5 vs 62.6 ± 2.4%). E/A ratios declined with age in males (1.6 ± 0.1 vs 1.3 ± 0.1; p < .05) but not females (1.4 ± 0.1 vs 1.3 ± 0.1) and this was accompanied by increased ventricular collagen levels in males. These changes in ejection fraction (r = 0.52; p = .01), septal wall thickness (r = 0.59; p = .002), E/A ratios (r = −0.49; p = .04), and fibrosis (r = 0.82; p = .002) were closely graded by frailty scores in males. Only septal wall thickness and LV mass increased with frailty in females. Serum cytokines changed modestly with age in both sexes. Nonetheless, in males, E/A ratios, LV mass, LV posterior wall thickness, and septal wall thickness increased as serum cytokines increased (eg, IL-6, IL-3, IL-1α, IL-1β, tumor necrosis factor-α, eotaxin, and macrophage inflammatory protein-1α), while ejection fraction declined with increasing IL-3 and granulocyte-macrophage colony stimulating factor. Cardiac outcomes were not correlated with inflammatory cytokines in females. Thus, changes in cardiac structure and function in late life are closely graded by both frailty and markers of inflammation, but this occurs primarily in males. This suggests poor overall health and inflammation drive maladaptive changes in older male hearts, while older females may be resistant to these adverse effects of frailty.

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Matthew A Allison ◽  
Jianwen Cai ◽  
Ankit Desai ◽  
Barry Hurwitz ◽  
Ai Ni ◽  
...  

Background: The purpose of this study was to determine the magnitudes and significances of the associations between adiposity and echocardiographically determined measures of left ventricular (LV) structure and function in a diverse cohort of Hispanic/Latino adults. Methods: Subjects were 1,350 adult men and women participants of the Hispanic Communities Health Study - Study of Latinos (HCHS-SOL) who enrolled in an ancillary study to determine cardiac structure and function by echocardiography. In addition to echocardiography, subjects were evaluated by extensive survey information, relevant physical measurements (to include bioelectrical impedance) and fasting blood assays. Results: The mean age was 56.1 years and 57% were female. Twenty-six percent were Mexican American, 25% Cuban American, 18% Dominican American, 17% Puerto Rican American, 8% Central American and 7% South American. Overall, the mean ejection fraction was 60.5%, while the mean stroke volume was 70 ml, end diastolic volume 83 ml, fractional shortening 31% and cardiac output 4.5 L/min. Results of multivariable linear regression adjusted for age, gender, hypertension, diabetes, dyslipidemia, cigarette smoking, family history of coronary heart disease, C-reactive protein and chronic kidney disease revealed that each 1-unit increment in body mass index (BMI) and fat mass (FM) by impedance was associated with 0.64 and 0.25 (p < 0.01 for both) higher LV mass index (to height), while a 0.1 unit increment in the waist to hip ratio (WHR) was associated with 3.2 higher LV mass index. Concomitantly, each 1-unit increment in BMI and FM was associated with 7 and 3% (p < 0.01 for each) higher odds of LV hypertrophy, while a 0.1 unit increment in WHR was associated with 78% higher odds for LV hypertrophy (p < 0.01). On the other hand, none of these variables were significantly associated with ejection fraction. There were no significant interactions between the anthropometric variables and the different Hispanic groups for LV mass index or hypertrophy. Conclusions: Among Hispanics/Latinos from different cultural backgrounds, and by three measures of body composition (BMI, FM and WHR), higher levels of adiposity are significantly associated with higher LV mass indexed for height and the odds for hypertrophy, while not being associated with better or worse ejection fraction.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Jeffrey R Misialek ◽  
Alvaro Alonso ◽  
Erin D Michos ◽  
Scott D Solomon ◽  
Amil M Shah ◽  
...  

Introduction: Fibroblast growth factor 23 (FGF23), an endocrine hormone, induced left ventricular (LV) hypertrophy through direct action in experimental animal models. The association of FGF23 with echocardiographic measures in humans is relatively uncharacterized. Hypothesis: Higher levels of FGF23 will be cross-sectionally associated with more adverse echocardiographic measures of LV structure and function. Methods: We conducted a cross-sectional analysis of 2086 African-American adults (66% female, median age 55) from a subset of the ARIC Study, a community-based cohort in the United States. Intact active FGF23 was assessed in blood samples collected at ARIC visit two (1990-1992). Echocardiography was performed at visit three (1993-1995) in participants recruited at the Jackson field center only. We used multivariable linear regression to evaluate the associations of FGF23 (per 15 pg/mL change) with echocardiographic measures after adjustment for traditional cardiovascular risk factors assessed at visit two. We also examined differences in observed associations by age and sex using interaction terms. Results: FGF23 was significantly associated with greater left atrial diameter and LV mass index (Table). A significant sex interaction was identified for LV diameter (p-interaction = 0.005). No association was observed in men while a positive association was observed among women. An adverse, decreasing trend in percent fractional shortening of the LV diameter at higher levels of FGF was stronger in individuals aged >55 (p-interaction = 0.03). No linear association was found between FGF23 and E/A ratio. Conclusion: FGF23 was associated with higher LV mass, larger LV size, and lower LV systolic function. These findings are consistent with results from experimental animal studies and provide evidence suggesting that cardiac structure and function may be influenced by FGF23 in humans. Prospective studies are needed to evaluate whether FGF23 is associated with change in markers of cardiac structure and function.


2014 ◽  
Vol 7 (1) ◽  
pp. 104-115 ◽  
Author(s):  
Amil M. Shah ◽  
Sanjiv J. Shah ◽  
Inder S. Anand ◽  
Nancy K. Sweitzer ◽  
Eileen O’Meara ◽  
...  

2014 ◽  
Vol 7 (5) ◽  
pp. 740-751 ◽  
Author(s):  
Amil M. Shah ◽  
Brian Claggett ◽  
Nancy K. Sweitzer ◽  
Sanjiv J. Shah ◽  
Inder S. Anand ◽  
...  

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Muhammad Oneeb Rehman Mian ◽  
Jean-Luc Bigras ◽  
Rafael Fernandes ◽  
Mariane Bertagnolli ◽  
Li Feng Xie ◽  
...  

Objective: Studies support a causal association between preterm birth and increased risk of cardiovascular diseases. Increased left and right ventricular mass and impaired systolic and diastolic function has been reported in young adults born preterm. However, the impact of extreme preterm birth and prematurity-specific complications on adult cardiac structure and function has not been evaluated. We assessed cardiac structure and function in young adults born extremely preterm (EPT) versus term, and correlated long term cardiac remodeling with neonatal bronchopulmonary dysplasia (BPD). Methods: Eighty five EPT (gest. age = 27.1±1.4 weeks) were recruited along with term-born controls matched for age, sex and socioeconomic status. Birth and neonatal data (gestational age, birth weight, BPD indicated by O 2 requirements at 36 weeks postmenstrual age) was collected. Ambulatory blood pressure (Spacelabs) and echocardiographic measurements (Phillips) were taken. Comparisons were performed using ANOVA or T-test. Results: EPT presented with increased systolic (119±9 vs 116±8 mmHg, P<0.05) and diastolic (68±5 vs 66±6 mmHg, P<0.05) blood pressures. EPT exhibited reduced septal thickness (IVS, 6.8±0.8 vs 7.1±1.1 mm, P<0.05), left ventricular internal dimension (LVID, 46±4 vs 48±5 mm, P<0.05), LV end-diastolic (98±20 vs 106±24 ml, P<0.05) and end-systolic (36±9 vs 40±11 ml, P<0.01) volumes, right ventricular internal dimension (RVID, 22±3 vs 24±4 mm, P<0.05), and LV mass (104±27 vs 115±30 g, P<0.05), but similar LV mass and volume indexes. EPT exhibited increased LV myocardial performance index (0.41±0.04 vs 0.39±0.04, P<0.01), reduced mitral lateral e’ (17.6±2.8 vs 19.1±2.6 cm/s, P<0.01), mitral s’ (10.7±2.3 vs 11.6±2.3 cm/s, P<0.01), tricuspid E’ (15.8±2.7 vs 16.8±2.1 cm/s, P<0.05), and tricuspid S’ (13.1±2.0 vs 14.0±2.0 cm/s, P<0.01) waves, and a trend in reduced mitral E wave (81±14 vs 85±15 cm/s, P=0.09). EPT with neonatal BPD exhibited greater reduction in IVS (6.5±0.8 mm, P<0.05 vs terms), LVID (45±4 mm, P<0.05), LV Mass (98±22 g, P<0.05), and RVID (20±3 mm, P<0.01). Conclusions: EPT exhibit cardiac structural and functional alterations compared to term-born individuals. Neonatal BPD in EPT is a key contributor to long term cardiac remodeling.


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