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OBJECTIVE--Fasting plasma glucose and risk of type 2 diabetes are higher among Indian Asians than among European and North American Caucasians. Few studies have investigated genetic factors influencing glucose metabolism among Indian Asians. RESEARCH DESIGN AND METHODS--We carried out genome-wide association studies for fasting glucose in 5,089 non-diabetic Indian Asians genotyped with the Illumina Hap610 BeadChip and 2,385 Indian Asians (698 with type 2 diabetes) genotyped with the Illumina 300 BeadChip. Results were compared with findings in 4,462 European Caucasians. RESULTS--We identified three single nucleotide polymorphisms (SNPs) associated with glucose among Indian Asians at P < 5 x [10.sup.-8], all near melatonin receptor MTNR1B. The most closely associated was rs2166706 (combined P = 2.1 x [10.sup.-9]), which is in moderate linkage disequilibrium with rs1387153 ([r.sup.2] = 0.60) and rs10830963 ([r.sup.2] = 0.45), both previously associated with glucose in European Caucasians. Risk allele frequency and effect sizes for rs2166706 were similar among Indian Asians and European Caucasians: frequency 46.2 versus 45.0%, respectively (P = 0.44); effect 0.05 (95% CI 0.01-0.08) versus 0.05 (0.03-0.07 mmol/l), respectively, higher glucose per allele copy (P = 0.84). SNP rs2166706 was associated with type 2 diabetes in Indian Asians (odds ratio 1.21 [95% CI 1.06-1.38] per copy of risk allele; P = 0.006). SNPs at the GCK, GCKR, and G6PC2 loci were also associated with glucose among Indian Asians. Risk allele frequencies of rs1260326 (GCKR) and rs560887 (G6PC2) were higher among Indian Asians compared with European Caucasians. CONCLUSIONS--Common genetic variation near MTNR1B influences blood glucose and risk of type 2 diabetes in Indian Asians. Genetic variation at the MTNR1B, GCK, GCKR, and G6PC2 loci may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians., The World Health Organization estimates that by 2025 there will be 57 million Indian Asians with type 2 diabetes, (1) by which time one-quarter of type 2 diabetic patients globally [...]

ObjectivesIn outpatients with suspected ischaemic symptoms, we investigated the impact of risk factor profile on the prognostic value of coronary artery calcium scoring (CACS) and CT coronary angiography (CTCA).Methods772 consecutive patients underwent CACS and CTCA; 52 patients (6.7%) with significant coronary artery lesions underwent revascularisation within 60 days and were excluded. 720 remaining patients were followed up for 38.1±17.4 months.ResultsLate presentation (after 60 days) major adverse cardiovascular events (MACEs) were recorded in 27 patients (3.8%). Hypertension was strongly associated with adverse outcomes (unadjusted HR 6.5 (2.9 to 14), p<0.001), and hypertensive patients had double the prevalence of non-calcified plaque versus normotensive individuals (30.2% vs 14.3%, p<0.001). Adjusting for confounders, severe stenosis at CTCA was predictive of MACE for normotensive and hypertensive patients (HR 9.6 (2.8 to 43.1), p<0.001, and HR 6.2 (2.4 to 16.1), p<0.001, respectively). CACS alone was not predictive of MACE throughout the cohort (HR 1.001 (0.9997 to 1.001), p=0.36) and when adjusting for confounders, a cut-off of CACS>400 predicted MACE in normotensive individuals (HR 10.6 (2.41 to 49.3), p<0.001) but not in hypertensive individuals (HR 1.3 (0.5 to 3.6), p=0.56). Zero calcium score did not mitigate the risk of MACE (HR 0.84 (0.39 to 1.8), p=0.65) and 13/27 patients (48.1%) who suffered MACE had a 0 calcium score; all had hypertension.ConclusionsIn low-risk patients with stable cardiovascular symptoms, CTCA provides important additive prognostic information over CACS, and CACS (including CACS>400) underestimated cardiovascular risk in patients with hypertension. This may relate to the increased prevalence of non-calcified plaque in these individuals.

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Background: To investigate the effects of Angiotensin II receptor blockade (ARB) and angiotensin converting enzyme (ACE) inhibition on platelet reactivity in patients with mild to moderate hypertension. PFA-100 evaluates platelet function (expressed in seconds as closure time, CT) in anti-coagulated whole blood in vitro at high shear rates. The test cartridge is impregnated with either collagen and epinephrine (Col/Epi) or collagen and ADP (Col/ADP). Methods: 33 patients were randomized to perindopril 4mg (n = 9), valsartan 80mg/d (n = 9) and for lifestyle modification (n = 15) for 4 weeks. Platelet reactivity was measured at baseline and after 4 weeks by PFA-100. Normotensive controls (n = 11) were also tested at baseline to standardize PFA-100 CT. Haematocrit, platelet count and plasma vWF antigen levels were measured. Results: There was no difference in baseline haematocrit, platelet count or vWF antigen level between the groups. The vWF antigen levels measured after 4 weeks showed no significant difference either. Significant blood pressure reduction was seen in the treated group (SBP P = 0.002 and DBP P = 0.005) when compared to the life style modification group (SBP P = 0.06 and DBP P = 0.04) after 4 weeks. There was no significant statistical difference in Col/ADP CT in treated and non-treated groups but increase in CT (P = 0.05) in treated group with Col/Epi seen after 4 weeks. Conclusion: In patients with mild to moderate hypertension, valsartan and perindopril compared to life style modification demonstrate a significant decrease in platelet reactivity.