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Impact of biological aging on arterial aging in American Indians: findings from the Strong Heart Family Study.

ABSTRACT: Telomere length, a marker of biological aging, has been associated with cardiovascular disease (CVD). Increased arterial stiffness, an indicator of arterial aging, predicts adverse CVD outcomes. However, the relationship between telomere length and arterial stiffness is less well studied. Here we examined the cross-sectional association between leukocyte telomere length (LTL) and arterial stiffness in 2,165 American Indians in the Strong Heart Family Study (SHFS). LTL was measured by qPCR. Arterial stiffness was assessed by stiffness index ?. The association between LTL and arterial stiffness was assessed by generalized estimating equation model, adjusting for sociodemographics (age, sex, education level), study site, metabolic factors (fasting glucose, lipids, systolic blood pressure, and kidney function), lifestyle (BMI, smoking, drinking, and physical activity), and prevalent CVD. Results showed that longer LTL was significantly associated with a decreased arterial stiffness (?=-0.070, P=0.007). This association did not attenuate after further adjustment for hsCRP (?=-0.071, P=0.005) or excluding participants with overt CVD (?=-0.068, P=0.012), diabetes (?=-0.070, P=0.005), or chronic kidney disease (?=-0.090, P=0.001). In summary, shorter LTL was significantly associated with an increased arterial stiffness, independent of known risk factors. This finding may shed light on the potential role of biological aging in arterial aging in American Indians.

SUBMITTER: Peng H

PROVIDER: S-EPMC5032684 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Impact of biological aging on arterial aging in American Indians: findings from the Strong Heart Family Study.

Peng Hao H Zhu Yun Y Yeh Fawn F Cole Shelley A SA Best Lyle G LG Lin Jue J Blackburn Elizabeth E Devereux Richard B RB Roman Mary J MJ Lee Elisa T ET Howard Barbara V BV Zhao Jinying J

Aging 20160801 8

Telomere length, a marker of biological aging, has been associated with cardiovascular disease (CVD). Increased arterial stiffness, an indicator of arterial aging, predicts adverse CVD outcomes. However, the relationship between telomere length and arterial stiffness is less well studied. Here we examined the cross-sectional association between leukocyte telomere length (LTL) and arterial stiffness in 2,165 American Indians in the Strong Heart Family Study (SHFS). LTL was measured by qPCR. Arter ...[more]

PMID: 27540694

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Project description:Background: Increased serum levels of C-reactive protein (CRP), an important component of the innate immune response, are associated with increased risk of cardiovascular disease (CVD). Multiple single nucleotide polymorphisms (SNP) have been identified which are associated with CRP levels, and Mendelian randomization studies have shown a positive association between SNPs increasing CRP expression and risk of colon cancer (but thus far not CVD). The effects of individual genetic variants often interact with the genetic background of a population and hence we sought to resolve the genetic determinants of serum CRP in a number of American Indian populations.Methods: The Strong Heart Family Study (SHFS) has serum CRP measurements from 2428 tribal members, recruited as large families from three regions of the United States. Microsatellite markers and MetaboChip defined SNP genotypes were incorporated into variance components, decomposition-based linkage and association analyses.Results: CRP levels exhibited significant heritability (h2 = 0.33 ± 0.05, p<1.3 X 10-20). A locus on chromosome (chr) 6, near marker D6S281 (approximately at 169.6 Mb, GRCh38/hg38) showed suggestive linkage (LOD = 1.9) to CRP levels. No individual SNPs were found associated with CRP levels after Bonferroni adjustment for multiple testing (threshold <7.77 x 10-7), however, we found nominal associations, many of which replicate previous findings at the CRP, HNF1A and 7 other loci. In addition, we report association of 46 SNPs located at 7 novel loci on chromosomes 2, 5, 6(2 loci), 9, 10 and 17, with an average of 15.3 Kb between SNPs and all with p-values less than 7.2 X 10-4.Conclusion: In agreement with evidence from other populations, these data show CRP serum levels are under considerable genetic influence; and include loci, such as near CRP and other genes, that replicate results from other ethnic groups. These findings also suggest possible novel loci on chr 6 and other chromosomes that warrant further investigation.

Project description:Essentials Plasminogen activator inhibitor-1 (PAI-1) advanced cellular senescence in experiment studies. No population study exists on the association between PAI-1 and biological aging in American Indians. We found cross-sectional and longitudinal associations between higher PAI-1 and shorter telomere length. Our findings suggest a pathway linking PAI-1 with biological aging beyond metabolic factors.SummaryBackground Plasminogen activator inhibitor-1 (PAI-1) promotes cellular aging both in vitro and in vivo. Telomere length is a marker of biological aging. Objectives To examine the cross-sectional and longitudinal associations between plasma PAI-1 and leukocyte telomere length in a large-scale epidemiological study of American Indians. Methods We measured leukocyte telomere length (LTL) and plasma PAI-1 in 2560 American Indians who were free of overt cardiovascular disease (CVD) and participated in the Strong Heart Family Study (SHFS) clinical examination in 2001-2003. LTL and PAI-1 were repeatedly measured in 475 participants who attended SHFS clinical visits in both 2001-2003 and 1998-1999. A generalized estimating equation model was used to examine the cross-sectional and longitudinal associations between PAI-1 and LTL, adjusting for known risk factors. Results A higher level of plasma PAI-1 was negatively associated with shorter age-adjusted LTL (β = -0.023; 95% CI, -0.034 to -0.013). This association was attenuated (β = -0.015; 95% CI, -0.029 to -0.002) after adjustments for demographics, study site, lifestyle (smoking, drinking and physical activity) and metabolic factors (obesity, blood pressure, fasting glucose, insulin, lipids and kidney function). Further adjustment for hsCRP did not change this association (β = -0.015; 95% CI, -0.029 to -0.001). Longitudinal analysis revealed that change in plasma PAI-1 was also inversely associated with change in LTL after adjusting for demographics, follow-up years, lifestyle factors, changes in metabolic factors, baseline levels of PAI-1 and LTL (β = -0.0005; 95% CI, -0.0009 to -0.0001). Conclusions A higher level of plasma PAI-1 was associated with shorter LTL in American Indians. This finding may suggest a potential role of PAI-1 in biological aging among American Indians.

Dataset Information

Impact of biological aging on arterial aging in American Indians: findings from the Strong Heart Family Study.

Publications

Impact of biological aging on arterial aging in American Indians: findings from the Strong Heart Family Study.

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