TY - JOUR
T1 - Sex and ethnic differences in 47 candidate proteomic markers of cardiovascular disease
T2 - The Mayo Clinic proteomic markers of arteriosclerosis study
AU - Kim, Charles X.
AU - Bailey, Kent R.
AU - Klee, George G.
AU - Ellington, Allison A.
AU - Liu, Guanghui
AU - Mosley, Thomas H.
AU - Rehman, Hamid
AU - Kullo, Iftikhar J.
N1 - Funding Information:
The Mayo Vascular Proteomics Program was funded by the National Heart, Lung and Blood Institute to investigate multimarker approaches for early detection of CVD. Protein markers (n = 47, see for abbreviations) were selected from pathways of inflammation, lipoprotein metabolism, adipocyte metabolism, hemodynamic stress, calcification and thrombosis. Markers were selected based on basic science, observational and clinical studies suggesting the roles of these markers in arteriosclerosis and in mediating end-organ damage in the context of hypertension. Uniplex and multiplex assays were used to measure the 47 markers in stored blood samples of 1324 African-American (AA) and 1237 non-Hispanic white (NHW) participants. In this report, we describe the associations of sex and ethnicity with circulating levels of these 47 protein markers.
PY - 2010/2/5
Y1 - 2010/2/5
N2 - Background: Cardiovascular disease (CVD) susceptibility differs between men and women and varies with ethnicity. This variability is not entirely explained by conventional CVD risk factors. We examined differences in circulating levels of 47 novel protein markers of CVD in 2561 men and women of African-American (AA) and non-Hispanic White (NHW) ethnicity, enrolled at geographically distinct sites. Methodology/Principal Findings: Participants (1,324 AAs, mean age 63.5 y, 71% women; 1,237 NHWs, mean age 58.9 y, 57% women) belonged to sibships ascertained on the basis of hypertension. Solid-phase immunoassays and immunoturbidometric, clot-based, chromogenic, and electrophoretic assays were used to measure the 47 protein markers in plasma or serum. Marker levels were log transformed and outliers were adjusted to within 4 SD. To identify markers independently associated with sex or ethnicity, we employed multivariable regression analyses that adjusted for conventional risk factors, prior history of CVD, medication use and lifestyle factors (physical activity, alcohol consumption and education). Generalized estimating equations were used to correct for intrafamilial correlations. After adjustment for the above covariates, female sex was associated with higher levels of 29 markers and lower levels of 6 markers. Female sex was independently associated with higher levels of several inflammatory markers as well as lipoproteins, adipokines, natriuretic peptides, vasoconstrictor peptides and markers of calcification and thrombosis. AA ethnicity was associated with higher levels of 19 markers and lower levels of 6 markers, including higher levels of several inflammatory makers, higher leptin and lower adiponectin levels, lower levels of vasodilator-natriuretic peptides, higher levels of vasoconstrictor-antidiuretic peptides and markers of calcification and thrombosis. Conclusions/Significance: Plasma levels of several novel protein markers of CVD differ significantly in the context of sex and ethnicity. These results have implications for individualized CVD risk assessment.
AB - Background: Cardiovascular disease (CVD) susceptibility differs between men and women and varies with ethnicity. This variability is not entirely explained by conventional CVD risk factors. We examined differences in circulating levels of 47 novel protein markers of CVD in 2561 men and women of African-American (AA) and non-Hispanic White (NHW) ethnicity, enrolled at geographically distinct sites. Methodology/Principal Findings: Participants (1,324 AAs, mean age 63.5 y, 71% women; 1,237 NHWs, mean age 58.9 y, 57% women) belonged to sibships ascertained on the basis of hypertension. Solid-phase immunoassays and immunoturbidometric, clot-based, chromogenic, and electrophoretic assays were used to measure the 47 protein markers in plasma or serum. Marker levels were log transformed and outliers were adjusted to within 4 SD. To identify markers independently associated with sex or ethnicity, we employed multivariable regression analyses that adjusted for conventional risk factors, prior history of CVD, medication use and lifestyle factors (physical activity, alcohol consumption and education). Generalized estimating equations were used to correct for intrafamilial correlations. After adjustment for the above covariates, female sex was associated with higher levels of 29 markers and lower levels of 6 markers. Female sex was independently associated with higher levels of several inflammatory markers as well as lipoproteins, adipokines, natriuretic peptides, vasoconstrictor peptides and markers of calcification and thrombosis. AA ethnicity was associated with higher levels of 19 markers and lower levels of 6 markers, including higher levels of several inflammatory makers, higher leptin and lower adiponectin levels, lower levels of vasodilator-natriuretic peptides, higher levels of vasoconstrictor-antidiuretic peptides and markers of calcification and thrombosis. Conclusions/Significance: Plasma levels of several novel protein markers of CVD differ significantly in the context of sex and ethnicity. These results have implications for individualized CVD risk assessment.
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U2 - 10.1371/journal.pone.0009065
DO - 10.1371/journal.pone.0009065
M3 - Article
C2 - 20140090
AN - SCOPUS:77949393795
SN - 1932-6203
VL - 5
JO - PLoS One
JF - PLoS One
IS - 2
M1 - e9065
ER -