HDL functionality in South Asians as compared to white Caucasians.

BACKGROUND AND AIMS: South 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 RESULTS: HDL 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 (1)H-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. CONCLUSION: Impaired HDL functionality in South Asians may be a contributing factor to their high CVD risk. CLINICAL TRIAL REGISTRATION: NTR 2473 (URL: http://www.trialregister.nl/).

Cardiovascular flexibility in middle-aged overweight South Asians vs. white Caucasians: response to short-term caloric restriction.

BACKGROUND AND AIMS: South Asians have a higher risk of developing cardiovascular disease than white Caucasians. The underlying cause is unknown, but might be related to higher cardiac susceptibility to metabolic disorders. Short-term caloric restriction (CR) can be used as a metabolic stress test to study cardiac flexibility. We assessed whether metabolic and functional cardiovascular flexibility to CR differs between South Asians and white Caucasians. METHODS AND RESULTS: Cardiovascular function and myocardial triglycerides were assessed using a 1.5T-MRI/S-scanner in 12 middle-aged overweight male South Asians and 12 matched white Caucasians before and after an 8-day very low calorie diet (VLCD). At baseline South Asians were more insulin resistant than Caucasians. Cardiac dimensions were smaller, despite correction for body surface area, and pulse wave velocity (PWV) in the distal aorta was higher in South Asians. Systolic and diastolic function, myocardial triglycerides and pericardial fat did not differ significantly between groups. After the VLCD body weight reduced on average by 4.0 ± 0.2 kg. Myocardial triglycerides increased in both ethnicities by 69 ± 18%, and diastolic function decreased although this was not significant in South Asians. However, pericardial fat and PWV in the proximal and total aorta were reduced in Caucasians only. CONCLUSION: Myocardial triglyceride stores in middle-aged overweight and insulin resistant South Asians are as flexible and amenable to therapeutic intervention by CR as age-, sex- and BMI-matched but less insulin resistant white Caucasians. However, paracardial fat volume and PWV showed a differential effect in response to an 8-day VLCD in favor of Caucasians. CLINICAL TRIAL REGISTRATION: NTR 2473 (URL: http://www.trialregister.nl/trialreg/admin/rctsearch.asp?Term=2473).

Radioactive iodine in the treatment of medullary thyroid carcinoma: a controlled multicenter study.

OBJECTIVE: Radioactive iodine (RAI) therapy in medullary thyroid carcinoma (MTC) is applied in some centers, based on the assumption that cross-irradiation from thyroid follicular cells may be beneficial. However, no systematic studies on the effect of RAI treatment in MTC have been performed. The aim of this study was to analyze the effect of RAI treatment on survival in MTC patients. DESIGN: Retrospective multicenter study in eight University Medical Centers in The Netherlands. METHODS: Two hundred and ninety three MTC patients without distant metastases who had undergone a total thyroidectomy were included between 1980 and 2007. Patients were stratified by clinical appearance, hereditary stage, screening status, and localization. All patients underwent regular surgical treatment with additional RAI treatment in 61 patients. Main outcome measures were disease-free survival (DFS) and disease-specific survival (DSS). Cure was defined as biochemical and radiological absence of disease. RESULTS: In multivariate analysis, stratification according to clinical appearance (P=0.72), hereditary stage (P=0.96), localization (P=0.69), and screening status (P=0.31) revealed no significant effects of RAI treatment on DFS. Multivariate analysis showed no significant difference in DSS for the two groups stratified according to clinical appearance (P=0.14). Owing to limited number of events, multivariate analysis was not possible for DSS in the other groups of stratification. CONCLUSIONS: Based on the results of the present analysis, we conclude that RAI has no place in the treatment of MTC.