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Plasma heat shock protein 60 and cardiovascular disease risk: the role of psychosocial, genetic, and biological factors.

ABSTRACT: The Whitehall Study is a prospective epidemiological study of cardiovascular risk factors in healthy members of the British Civil Service, which has identified psychological distress as a major risk factor for coronary heart disease. The levels of circulating Hsp60 in 860 participants from the Whitehall cohort and 761 individuals diagnosed with diabetes have been measured and related to psychological, biological, and genetic factors. In the Whitehall participants, concentrations of Hsp60 ranged from undetectable to mg/mL levels. Circulating Hsp60 correlated with total and low-density lipoprotein (LDL) cholesterol and was positively associated with a flattened slope of cortisol decline over the day. Levels of this stress protein also correlated with measures of psychological stress including psychological distress, job demand, and low emotional support. Mass spectrometric analysis of circulating immunoreactive Hsp60 reveal that it is predominantly the intact protein with no mitochondrial import peptide, suggesting that this circulating protein emanates from mitochondria. The Hsp60 is stable when added to plasma and the levels in the circulation of individuals are remarkably constant over a 4-year period, suggesting plasma levels are partly genetically controlled. Sequence analysis of the HSP60-HSP10 intergenic promoter region identified a common variant 3175 C>G where the G allele had a frequency of 0.30 and was associated with higher Hsp60 levels in 761 type 2 diabetic patients. The extended range of plasma Hsp60 concentrations in the general population is genuine and is likely to be related to genetic, biological, and psychosocial risk factors for coronary artery disease.

SUBMITTER: Shamaei-Tousi A

PROVIDER: S-EPMC2134800 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Plasma heat shock protein 60 and cardiovascular disease risk: the role of psychosocial, genetic, and biological factors.

Shamaei-Tousi Alireza A Steptoe Andrew A O'Donnell Katie K Palmen Jutta J Stephens Jeffrey W JW Hurel Steven J SJ Marmot Michael M Homer Karen K D'Aiuto Francesco F Coates Anthony R M AR Humphries Steve E SE Henderson Brian B

Cell stress & chaperones 20070101 4

The Whitehall Study is a prospective epidemiological study of cardiovascular risk factors in healthy members of the British Civil Service, which has identified psychological distress as a major risk factor for coronary heart disease. The levels of circulating Hsp60 in 860 participants from the Whitehall cohort and 761 individuals diagnosed with diabetes have been measured and related to psychological, biological, and genetic factors. In the Whitehall participants, concentrations of Hsp60 ranged ...[more]

PMID: 18229457

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Project description:Background: Cardiovascular disease (CVD) is a complex disease resulting from multiscale risk factors including genetics, age, and psychosocial factors (PSFs) such as depression and social isolation. However, previous research has lacked in operationalizing multiscale risk factors to determine individual and interactive associations over the life course. Therefore, this study aimed to evaluate individual and interactive associations of multiscale risk factors for CVD outcomes including genetics and PSFs at middle and older-aged stages of the life course. Methods: Baseline data from the Canadian Longitudinal Study on Aging (CLSA; n = 9,892 with genome-wide genotyping data) was used for this investigation. A 39 single nucleotide polymorphism polygenic risk score (PRS) for CVD was constructed. PSFs consisted of: (1) Depressive symptoms categorized into: "none" (Group 1, reference), "current" (Group 2), "clinical depression with no current symptoms" (Group 3), and "potential, recurrent depression" (Group 4); and (2) Social isolation index as a binary variable comprised of marital status, living arrangements, retirement status, contacts, and social participation. Heart-related disorders (HRD: myocardial infarction, angina and heart disease) was the primary outcome of interest and peripheral/vascular-related disorders (PVRD: stroke, peripheral vascular disease and hypertension) was the secondary outcome. Multivariable logistic regression models adjusted for socio-demographic factors were conducted stratified by age group (middle-aged: 45-69 years, older-aged: ≥70 years). Results: PRS was associated with HRD among middle- and older-aged participants [OR (95% confidence interval)] [1.06 (1.03-1.08), 1.06 (1.03-1.08), respectively]. Most depressive symptoms groups compared to the reference associated with HRD and PVRD, but only Group 4 associated with PVRD among older-aged [1.69 (1.08-2.64)]. Social isolation was associated with only PVRD among middle-aged [1.84 (1.04-3.26)]; however, socially isolated CLSA participants were underrepresented in the genotyped cohort (1.2%). No significant PRS*PSFs interactions were observed. Conclusions: Genetics and PSFs are independently associated with CVD. Varying observations across age groups underscores the need to advance research on multiscale risk factors operating both at a given point in time and over the life course. Future cohort studies may benefit from use of mobile assessment units to enable better reach to socially isolated participants for collection of biospecimens.

Dataset Information

Plasma heat shock protein 60 and cardiovascular disease risk: the role of psychosocial, genetic, and biological factors.

Publications

Plasma heat shock protein 60 and cardiovascular disease risk: the role of psychosocial, genetic, and biological factors.

Similar Datasets

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