Intensive Lifestyle Modification Reduces Lp-PLA2 in Dyslipidemic HIV/HAART Patients

Abstract

Patients with dyslipidemia associated with HIV-1 infection and highly active antiretroviral therapy (HAART) have elevated levels of Lp-PLA2 and CCL5/RANTES, which may increase risk of cardiovascular disease. Purpose This study aimed to determine whether an intensive diet and exercise (D/E) program, independently or combined with fenofibrate or niacin, could reduce Lp-PLA2 or RANTES. Methods Hypertriglyceridemic HIV patients on stable HAART (n=107) were randomized to one of five interventions: 1) Usual Care (UC); 2) D/E with placebos; 3) D/E with fenofibrate and placebo; 4) D/E with niacin and placebo; or 5) D/E with fenofibrate and niacin for 24 weeks. Lp-PLA2 and RANTES concentrations were measured in fasting plasma samples at baseline and post-intervention. General linear models were used to compare Lp-PLA2 and RANTES levels between the five groups post-intervention, controlling for baseline levels, age, BMI, CD4+ T-cell count, viral load, duration of infection, and HAART. Results At baseline, fasting plasma Lp-PLA2 (388.5 ± 127.5 ng/mL) and RANTES (43.8 ± 25.5 ng/mL) levels were elevated when compared to healthy controls. Post-treatment Lp-PLA2 mass was lower in patients who received D/E only (323.0 ± 27.2 ng/mL), D/E plus fenofibrate (327.2 ± 25.9 ng/mL) and D/E plus niacin (311.1 ± 27.8 ng/mL) when compared to patients receiving UC (402.2 ± 25.3 ng/mL). RANTES concentrations were not significantly affected by any intervention. Conclusions Elevated plasma Lp-PLA2 mass can be reduced by an intensive diet and exercise program in patients with HIV/HAART-associated dyslipidemia. RANTES is elevated but is not reduced by lifestyle modification, fenofibrate or niacin.

PPAR-α Agonist Fenofibrate Decreased RANTES Levels in Type 2 Diabetes Patients with Hypertriglyceridemia

“…After controlling for confounders, increased hsCRP levels and T2DM with hypertriglyceridemia were independently related to high serum RANTES levels. Our findings agree with studies indicating that circulating RANTES was significantly higher in patients with hypertriglyceridemia [ 23 ] or with T2DM [ 24 ] compared with controls, and was positively related to FBG [ 25 ]. Furthermore, our finding that serum RANTES was positively associated with Hcy support our previous result that the circulating RANTES levels were elevated in hyperhomocysteinemia patients compared with controls [ 15 ].…”

Atorvastatin Decreased Circulating RANTES Levels in Impaired Glucose Tolerance Patients with Hypercholesterolemia: An Interventional Study

“…This finding is similar to our previous results that RANTES levels were significantly higher in type 2 diabetes patients with hypertriglyceridemia compared with controls [8], and aligns with some other studies indicating that circulating RANTES levels were significantly higher in patients with dyslipidemia [21], hyperglycemia [22, 23], or metabolic syndrome [24] compared with controls. Our present study also documented that PFP RANTES levels were positively correlated with the levels of TC, TG, FBG, 2hPG, and HbA1c, but negatively related to the levels of HDL-C, which supported that RANTES might be associated with disorders of metabolism.…”

Phospholipases: at the crossroads of the immune system and the pathogenesis of HIV-1 infection

“…In keeping with the results obtained in vitro, several in vivo studies have demonstrated increased PLA 2 activation, as well as higher levels of AA and its metabolites, in HIV-1-infected individuals. In particular, these patients, compared with healthy controls, presented with higher plasma sPLA 2 and Lp-PLA 2 levels or increased enzymatic activity, associated with an enhanced risk of cardiovascular disease [199][200][201][202][203][204]. The effect of different antiretroviral regimens on plasma Lp-PLA 2 levels was investigated by several groups [205][206][207][208][209][210][211].…”