Abstract

Background and AimsSouth Asians have an exceptionally high risk of developing cardiovascular disease compared to white Caucasians. A contributing factor might be dysfunction of high density lipoprotein (HDL). We aimed to compare HDL function in different age groups of both ethnicities. Methods and ResultsHDL functionality with respect to cholesterol efflux, anti-oxidation and anti-inflammation was determined using fasting, apoB-depleted, plasma samples from South Asian and white Caucasian neonates (n = 14 each), adolescent healthy men (n = 12 each, 18–25 y), and adult overweight men (n = 12 each, 40–50 y). Adolescents were subjected to a 5-day high fat high calorie diet (HCD) and adults to an 8-day very low calorie diet (LCD). Additionally, HDL composition was measured in adolescents and adults using 1H-NMR spectroscopy. Anti-oxidative capacity was lower in South Asian adults before LCD (19.4 ± 2.1 vs. 25.8 ± 1.2%, p = 0.045, 95%-CI = [0.1; 12.7]) and after LCD (16.4 ± 2.4 vs. 27.6 ± 2.7%, p = 0.001, 95%-CI = [4.9; 17.5]). Anti-inflammatory capacity was reduced in South Asian neonates (23.8 ± 1.2 vs. 34.9 ± 1.3%, p = 0.000001, 95%-CI = [−14.6; −7.5]), and was negatively affected by an 8-day LCD only in South Asian adults (−12.2 ± 4.3%, p = 0.005, 95%-CI = [−5.9; −1.2]). Cholesterol efflux capacity was increased in response to HCD in adolescents (South Asians: +6.3 ± 2.9%, p = 0.073, 95%-CI = [−0.02; 0.46], Caucasians: +11.8 ± 3.4%, p = 0.002, 95%-CI = [0.17;0.65]) and decreased after LCD in adults (South Asians: −10.3 ± 2.4%, p < 0.001, 95%-CI = [−0.57; −0.20], Caucasians: −13.7 ± 1.9%, p < 0.00001, 95%-CI = [−0.67; −0.33]). Although subclass analyses of HDL showed no differences between ethnicities, cholesterol efflux correlated best with cholesterol and phospholipid within small HDL compared to other HDL subclasses and constituents. ConclusionImpaired HDL functionality in South Asians may be a contributing factor to their high CVD risk. Clinical Trial RegistrationNTR 2473 (URL: http://www.trialregister.nl/).

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