Soluble CD14 Levels in the Jackson Heart Study: Associations With Cardiovascular Disease Risk and Genetic Variants.
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ABSTRACT:
SUBMITTER: Stanislawski MA
PROVIDER: S-EPMC8159903 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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Soluble CD14 Levels in the Jackson Heart Study: Associations With Cardiovascular Disease Risk and Genetic Variants.
Stanislawski Maggie A MA Lange Leslie A LA Raffield Laura M LM Zakai Neil A NA Meyer Mariah M Ferrier Kendra K Szeto Mindy D MD Leavitt Colton C Shortt Jonathan A JA Thornton Timothy A TA Tracy Russell P RP Auer Paul L PL Reiner Alex P AP Lange Ethan M EM Olson Nels C NC
Arteriosclerosis, thrombosis, and vascular biology 20210429 6
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Project description:ObjectivesEvaluate the relationship between cardiovascular disease (CVD) risk factors and cochlear function in African Americans.MethodsRelationships between hearing loss, cochlear function, and CVD risk factors were assessed in a cross-sectional analysis of 1106 Jackson Heart Study participants. Hearing loss was defined as puretone average (PTA0.5,1,2,4) > 15 dB HL. Distortion product otoacoustic emissions (DPOAEs) were collected for f 2 = 1.0-8.0 kHz. Two amplitude averages were computed: DPOAElow (f 2 ≤ 4 kHz) and DPOAEhigh (f 2 ≥ 6 kHz). Based on major CVD risk factors (diabetes, current smoking, total cholesterol ≥240 mg/dL or treatment, and systolic blood pressure [BP]/diastolic BP ≥ 140/≥90 mmHg or treatment), four risk groups were created: 0, 1, 2, and ≥3 risk factors. Logistic regression estimated the odds of hearing loss and absent/reduced DPOAElow and DPOAEhigh by CVD risk status adjusting for age, sex, education, BMI, vertigo, and noise exposure.ResultsWith multivariable adjustment, diabetes was associated with hearing loss (OR = 1.48 [95% CI: 1.04-2.10]). However, there was not a statistically significant relationship between CVD risk factors (individually or for overall risk) and DPOAEs.ConclusionDiabetes was associated with hearing loss. Neither individual CVD risk factors nor overall risk showed a relationship to cochlear dysfunction.Level of evidence2b.
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Project description:ObjectiveExperimental studies have implicated soluble (s)CD14, an effector of lipopolysaccharide-induced inflammation, in insulin resistance, but its role in human metabolic endotoxemia has not been studied. We evaluated sCD14 in relation to dysglycemia in older adults and how this compares to other markers of inflammation.Research design and methodsWe investigated associations of sCD14, interleukin-6 (IL-6), CRP, and white blood cell (WBC) count with insulin resistance (quantitative insulin-sensitivity check index and HOMA 2 of insulin resistance) and incident type 2 diabetes in a population-based cohort of older adults. We also assessed the causal role of sCD14 in insulin resistance using an instrumental variable approach by Mendelian randomization.ResultsAfter adjustment for conventional risk factors, each of the four biomarkers showed positive cross-sectional associations with both insulin resistance measures. These associations persisted after mutual adjustment for all markers except sCD14. Over a median follow-up of 11.6 years, 466 cases of diabetes occurred. All biomarkers except sCD14 were positively associated with diabetes, although only WBC count remained associated (hazard ratio 1.43 per doubling [95% CI 1.07, 1.90]) after mutual adjustment. Instrumental variable analysis did not support a causal role for sCD14 in insulin resistance.ConclusionsAmong older adults, sCD14 was associated with insulin resistance, but this disappeared after adjustment for other biomarkers, showed no evidence of a causal basis, and was not accompanied by a similar association with diabetes. IL-6, CRP, and WBC count were each associated with insulin resistance and diabetes, WBC count most robustly. These findings do not support a central role for sCD14, but they highlight the preeminence of WBC count as an inflammatory measure of diabetes risk in this population.
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Project description:ObjectiveCD14 is a glycosylphosphotidylinositol-anchored membrane glycoprotein expressed on neutrophils and monocytes/macrophages that also circulates as a soluble form (sCD14). Despite the well-recognized role of CD14 in inflammation, relatively little is known about the genetic determinants of sCD14 or the relationship of sCD14 to vascular- and aging-related phenotypes.Methods and resultsWe measured baseline levels of sCD14 in >5000 European-American and black adults aged 65 years and older from the Cardiovascular Health Study, who were well characterized at baseline for atherosclerotic risk factors and subclinical cardiovascular disease, and who have been followed for clinical cardiovascular disease and mortality outcomes up to 20 years. At baseline, sCD14 generally showed strong positive correlations with traditional cardio-metabolic risk factors and with subclinical measures of vascular disease such as carotid wall thickness and ankle-brachial index (independently of traditional cardiovascular disease risk factors), and was also inversely correlated with body mass index. In genomewide association analyses of sCD14, we (1) confirmed the importance of the CD14 locus on chromosome 5q21 in European-American; (2) identified a novel African ancestry-specific allele of CD14 associated with lower sCD14 in blacks; and (3) identified a putative novel association in European-American of a nonsynonymous variant of PIGC, which encodes an enzyme required for the first step in glycosylphosphotidylinositol anchor biosynthesis. Finally, we show that, like other acute phase inflammatory biomarkers, sCD14 predicts incident cardiovascular disease, and strongly and independently predicts all-cause mortality in older adults.ConclusionsCD14 independently predicts risk mortality in older adults.
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Project description:BackgroundThe lifetime risk of heart failure (HF) is higher in the black population than in other racial groups in the United States.Methods and resultsWe measured the Life's Simple 7 ideal cardiovascular health metrics in 4195 blacks in the JHS (Jackson Heart Study; 2000-2004). We evaluated the association of Simple 7 metrics with incident HF and left ventricular structure and function by cardiac magnetic resonance (n=1188). Mean age at baseline was 54.4 years (65% women). Relative to 0 to 2 Simple 7 factors, blacks with 3 factors had 47% lower incident HF risk (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.39-0.73; P<0.0001); and those with ≥4 factors had 61% lower HF risk (HR, 0.39; 95% CI, 0.24-0.64; P=0.0002). Higher blood pressure (HR, 2.32; 95% CI, 1.28-4.20; P=0.005), physical inactivity (HR, 1.65; 95% CI, 1.07-2.55; P=0.02), smoking (HR, 2.04; 95% CI, 1.43-2.91; P<0.0001), and impaired glucose control (HR, 1.76; 95% CI, 1.34-2.29; P<0.0001) were associated with incident HF. The age-/sex-adjusted population attributable risk for these Simple 7 metrics combined was 37.1%. Achievement of ideal blood pressure, ideal body mass index, ideal glucose control, and nonsmoking was associated with less likelihood of adverse cardiac remodeling by cardiac magnetic resonance.ConclusionsCardiovascular risk factors in midlife (specifically elevated blood pressure, physical inactivity, smoking, and poor glucose control) are associated with incident HF in blacks and represent targets for intensified HF prevention.
| S-EPMC5319800 | biostudies-literature
Project description:IntroductionThe epidemiology of American Heart Association ideal cardiovascular health (CVH) metrics has not been fully examined in African Americans. This study examines the associations of CVH metrics with incident cardiovascular disease (CVD) in the Jackson Heart Study, a longitudinal cohort study of CVD in African Americans.MethodsJackson Heart Study participants without CVD (n=4,702) were followed prospectively between 2000 and 2011. Incidence rates and Cox proportional hazard ratios estimated risks for incident CVD (myocardial infarction, stroke, cardiac procedures, and CVD mortality) associated with seven CVH metrics by sex. Analyses were performed in 2015.ResultsParticipants were followed for a median of 8.3 years; none had ideal health on all seven CVH metrics. The prevalence of ideal health was low for nutrition, physical activity, BMI, and blood pressure metrics. The age-adjusted CVD incidence rate (IR) per 1,000 person years was highest for individuals with the least ideal health metrics: zero to one (IR=12.5, 95% CI=9.7, 16.1), two (IR=8.2, 95% CI=6.5, 10.4), three (IR=5.7, 95% CI=4.2, 7.6), and four or more (IR=3.4, 95% CI=2.0, 5.9). Adjusting for covariates, individuals with four or more ideal CVH metrics had lower risks of incident CVD compared with those with zero or one ideal CVH metric (hazard ratio, 0.29; 95% CI=0.17, 0.52; p<0.001).ConclusionsAfrican Americans with more ideal CVH metrics have lower risks of incident CVD. Comprehensive preventive behavioral and clinical supports should be intensified to improve CVD risk for African Americans with few ideal CVH metrics.
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