Access Type

Open Access Embargo

Date of Award

1-1-2019

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Nutrition and Food Science

First Advisor

Pramod . Khosla

Abstract

Maintenance hemodialysis (MHD) patients experience various abnormalities such as systemic inflammation (SI), oxidative stress (OS), and dyslipidemia (D). Defined as an imbalance of plasma lipids, lipoproteins, and lipid metabolism enzymes, D has been associated with a rise in morbidity and mortality within ESRD patients due to cardiovascular disease (CVD). However, the contribution of each of these parameters to D is poorly understood; moreover, the impact of the following parameters on dyslipidemia in different ethnicities is unknown. Hence, the objective of this study was to characterize D in a multi-ethnic cohort of ESRD patients. We hypothesized that the degree of dyslipidemia in MHD patients would be associated with abnormal lipoprotein particles and higher inflammation. The rationale for the proposed study is that once a dyslipidemic MHD profile is determined, targeted dietary interventions could be used to manage it. The degree of D was investigated in a cohort comprised of African American (AA), Malaysian-Malays (MM), Malaysian-Chinese (MC), and Malaysian-Indians (MI), of whom were enrolled in the PATCH clinical trial USA and/or Malaysia.

Lipids, lipoprotein particles, associated enzymes cholesteryl ester transfer protein (CETP), Lecithin-cholesterol acyltransferase (LCAT), as well as an inflammatory marker C-reactive protein (CRP), were measured. Assessment of dyslipidemia was based on the criteria from the Adult Treatment Panel (ATP III) guidelines. TAG/HDL ratios (≥ or < 3.8) were utilized to ascertain LDL phenotypes.

All lipid parameters in both groups were within the normal range; however, AA subjects had lower triglycerides (TAG) levels and higher high-density lipoprotein – cholesterol (HDL-C) when compared to Malaysian patients. Additionally, a biphasic response was recognized with regards to the relationship between TAG and HDL; as one rises, the other falls. Dyslipidemic analyses showed that all lipid values, in the TAG/HDL-C ratio ≥ 3.8 group were significantly different from the corresponding values in the < 3.8 TAG/HDL ratio group. The effect of dyslipidemia in the subfractions showed a decline in L-HDL and I-HDL consequently, S-HDL increased. Also, D increased VLDL and IDL subfractions, as well as I-LDL and S-LDL. Due to dyslipidemia, the mean LDL particle size decreased significantly in diameter, wherein 63% of patients were more likely to have a phenotype “B” LDL particle; which has been linked to the atherogenic small dense LDL. CETP activity was different amongst ethnicities and declined in the ≥ 3.8 TAG/HDL ratio group. LCAT activity was higher in AA with respect to Malaysians patients and was not affected by dyslipidemia. All patients had significantly elevated CRP levels, of which AA was the highest.

In conclusion, we analyzed lipids, lipoproteins, CETP, and LCAT activities, for a multi-ethnic cohort study, in addition to measuring CRP. For future directions, it would be ideal to investigate the effect of D on Apolipoprotein-A1, PON1, and, most important, test for HDL functionality.

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