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Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community.

ABSTRACT: Clinical trials using cholesteryl ester transfer protein (CETP) inhibitors to raise high-density lipoprotein cholesterol (HDL-C) concentrations reported an 'off-target' blood pressure (BP) raising effect. We evaluated the relations of baseline plasma CETP activity and longitudinal BP change.One thousand, three hundred and seven Framingham Study participants free of cardiovascular disease attending consecutive examinations 4 years apart (mean age 48 years) had baseline plasma CETP activity related to change in BP over the 4-year interval, adjusting for standard risk factors. Systolic BP increased [median +2 mmHg, 95% confidence interval (CI) -16,+23 mmHg], whereas diastolic BP decreased (median -3 mmHg, 95% CI -15,+11 mmHg). Plasma CETP activity was not related to change in diastolic BP, but was inversely related to change in systolic BP that was borderline significant (P=0.09). On multivariable analyses, plasma CETP activity was inversely related to change in pulse pressure (PP; beta per SD increment= -0.71 mmHg, P=0.005). When dichotomized at the median, plasma CETP activity above the median was associated with a 1 mmHg lower PP on follow-up (P=0.045).Decreasing plasma CETP activity was modestly related to increasing PP on follow-up in our community-based sample, suggesting that inhibition of intrinsic CETP activity itself is likely associated with minimal changes in BP.

SUBMITTER: Zachariah JP

PROVIDER: S-EPMC3204923 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community.

Zachariah Justin P JP Pencina Michael J MJ Lyass Asya A Kaur Guneet G D'Agostino Ralph B RB Ordovas Jose M JM Vasan Ramachandran S RS

Journal of hypertension 20110501 5

<h4>Objective</h4>Clinical trials using cholesteryl ester transfer protein (CETP) inhibitors to raise high-density lipoprotein cholesterol (HDL-C) concentrations reported an 'off-target' blood pressure (BP) raising effect. We evaluated the relations of baseline plasma CETP activity and longitudinal BP change.<h4>Methods and results</h4>One thousand, three hundred and seven Framingham Study participants free of cardiovascular disease attending consecutive examinations 4 years apart (mean age 48 y ...[more]

PMID: 21430561

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Project description:Reports of two independent studies suggest that familial hyperalphalipoproteinaemia (FHALP) may be caused by a deficiency of cholesteryl ester transfer/exchange activity (CETP). We also have studied CETP in the plasma of an Italian FHALP kindred. The study group was divided into blood relatives with greater than 1.70 mM high-density-lipoprotein cholesterol (HDL-C) (group I, n = 9), with less than 1.70 mM-HDL-C (group II, n = 12) and in spouses (group III, n = 6). Two different assays were performed to measure CETP activity. In method A the interfering endogenous lipoproteins in the plasma samples were removed by poly(ethylene glycol) precipitation or by ultracentrifugation at a relative density (d) of 1.180. The CETP-activity of these samples was measured in a system consisting of fixed amounts of HDL and cholesteryl [1-14C]oleate-labelled low-density lipoproteins (LDL). In method B, trace amounts of HDL (radiolabelled with cholesteryl [1-14C]oleate) were incubated with plasma for 3 h at 37 degrees C and the distribution of the label among lipoproteins was measured (CET activity). The results can be summarized as follows. The mean CETP activities measured by method A were 187, 213 and 243 nmol/h per ml in groups I, II and III respectively. The proband with the highest HDL-C (4.98 mM) had a CETP activity of 231 nmol/h per ml. The corresponding CET activities measured by method B and expressed as percentage transfer/h were 4.3, 8.0 and 11.2 in groups I-III. The proband with HDL-C = 4.98 mM had a value of only 1.7%/h. There was a strong negative correlation between percentage CE transfer and HDL-C concentration. Calculating these data in terms of CE exchange (nmol/h per ml), groups I, II and III exhibited mean activities of 86, 124 and 110 nmol/h per ml respectively; for the proband this value was 80 nmol/h per ml. Only a slight correlation was found between these values and the HDL-C value. Thus by both methods, (A), measuring the CETP activity per se and (B), measuring the activity in whole plasma (reflecting the activity of the protein and the concentration and composition of lipoproteins), no major differences could be found between the three groups. In our family, therefore, no connection between FHALP and CETP deficiency could be found. It is concluded that, for hyper- and dys-lipoproteinaemic samples, a careful selection of the assay procedure as well as the mode of calculating results is essential. Since this may not hold the previous studies, the supposed connection between FHALP and CETP deficiency is challenged.

Dataset Information

Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community.

Publications

Circulating plasma cholesteryl ester transfer protein activity and blood pressure tracking in the community.

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