Subclinical atherosclerosis and endothelial dysfunction in young South-Asian patients with systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE), especially Asian Indians, are at increased risk of developing premature atherosclerosis. To find out the prevalence and predictors of carotid intima-medial thickness (IMT) and brachial artery flow-mediated dilatation (FMD). Endothelial dysfunction was assessed by FMD in brachial artery and IMT was measured in common carotid artery in SLE patients and healthy controls. Sixty SLE patients (mean age 31 ± 9 years) and 38 healthy controls (mean age 34 ± 6 years) were included. The IMT was higher in SLE patients as compared to controls (0.49 ± 0.08 mm vs. 0.39 ± 0.05 mm, p < 0.0001). SLE and damage were independent predictors of abnormal IMT. FMD was impaired in SLE patients compared to controls (9.97% vs. 18.97%, p < 0.00001). None of the classical cardiovascular risk factors were predictors of FMD or abnormal IMT. Indian patients with SLE have higher prevalence of subclinical atherosclerosis and endothelial dysfunction. Presence of damage was associated with abnormal IMT in SLE patients.     

Contribution of VKORC1 and CYP2C9 polymorphisms in the interethnic variability of warfarin dose in Malaysian populations

Within the Asian populations, Indian patients had been reported to require higher warfarin dose compared with the Chinese and Malay patients, and this could not entirely be explained by cytochrome P450 (CYP)2C9 gene variants. Genetic variants of vitamin K epoxide oxidase reductase complex subunit 1 (VKORC1) has been well established as one of key determinants in the different responses of warfarin amongst patients. Adult patients who attended an anticoagulation clinic with stable INR were recruited. VKORC1 and CYP2C9 genotype were sequenced, and clinical characteristics were assessed. A total of 91 Malays, 96 Chinese, and 46 Indian patients were recruited. The mean age was 55 years and 51.5% were males. The mean dose of warfarin for all patients was 3.7 mg, and the mean daily dose of warfarin was significantly higher in Indians compared with the Chinese and Malay patients, 4.9 versus 3.5 and 3.3 mg, respectively (p < 0.001). VKORC1 GG genotype was more commonly seen in Indian patients. The mean warfarin dose in patients with GG genotype required a significant higher warfarin dose compared with those with AG and AA genotype (4.9 vs. 3.7 vs. 3.1 mg, respectively; p < 0.001). CYP2C9*2 and *3 is associated with a lower maintenance dose, 2.9 versus 3.7 mg in CYP2C9*1; p < 0.01. In multivariate analysis, age, ethnic groups, and genotypes had a significant influence on the required warfarin dose. In conclusion, VKORC1 and CYP2C9 polymorphism contribute to the difference dose requirement amongst the patients but other additional possible factors may play a role in the Indian race.     

Cilostazol reduces the progression of carotid intima-media thickness without increasing the risk of bleeding in patients with acute coronary syndrome during a 2-year follow-up

Cilostazol, a phosphodiesterase III inhibitor, is known to have anti-proliferative activity. We investigated the effects of cilostazol 200 mg, in addition to aspirin 100 mg and clopidogrel 75 mg, on carotid intima-media thickness (IMT) progression during a 2-year follow-up period in patients with acute coronary syndrome (ACS) requiring stent implantation. Patients with ACS (n = 130) were randomly assigned to the cilostazol group (n = 64) or the control group (n = 66). Longitudinal images of left and right carotid IMT were measured at baseline, at 6, 12, and 24 months using a 10-MHz linear vascular probe. The primary endpoint was to compare the changes in maximum carotid IMT at 2 years. Other parameters such as inflammatory markers [interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), and adiponectin] and bleeding risk were also compared. The carotid IMT showed no significant progression from baseline in the cilostazol group compared to significant progression in the control group at 12 months (0.78 ± 0.38 and 0.85 ± 0.41 mm, p = 0.034, respectively) and 24 months (0.82 ± 0.41 and 0.96 ± 0.39 mm, p = 0.022, respectively). Major bleeding (p = 1.00), minor bleeding (p = 0.68), and total bleeding rates (p = 0.74) were similar between the two groups during the 2-year follow-up. Decreases from baseline in IL-6 (−2.79 ± 2.83 and −2.14 ± 3.36 pg/ml, p = 0.010, respectively) and TNF-α (−2.81 ± 1.97 and −2.21 ± 2.68 pg/ml, p = 0.029, respectively) were significantly greater in the cilostazol group than the control group during the follow-up. Cilostazol treatment, with greater anti-inflammatory effect, inhibited the progression of carotid IMT without increasing the risk of bleeding in patients with ACS during the 2-year follow-up.     

Elevated plasma phospholipid transfer protein activity is a determinant of carotid intima-media thickness in type 2 diabetes mellitus

Aim/hypothesis The plasma activity of phospholipid transfer protein (PLTP), which has putative pro- and anti-atherogenic roles in lipoprotein metabolism, is increased in type 2 diabetes mellitus. We analysed the relationship between carotid artery intima–media thickness (IMT), an established marker of atherosclerosis, and PLTP activity in diabetic patients and control subjects. Methods The IMT (mean of three segments in both carotid arteries by ultrasonography), clinical variables, plasma PLTP activity (phospholipid vesicle–HDL system), lipoproteins, C-reactive protein and insulin were measured in 87 non-smoking men and women, who had type 2 diabetes mellitus, no cardiovascular disease, and were not on insulin or lipid-lowering medication, and in 83 age-matched control subjects. Results In diabetic patients, carotid IMT (p=0.02), pulse pressure (p=0.003), plasma PLTP activity (p<0.001), triglycerides (p=0.01), C-reactive protein (p<0.01) and insulin (p<0.001) were higher, whereas HDL cholesterol was lower (p<0.001) than in control subjects. Multiple stepwise linear regression analysis demonstrated that in type 2 diabetic patients IMT was independently associated with age (p<0.001), sex (p=0.001), pulse pressure (p=0.003), plasma PLTP activity (p=0.03) and HDL cholesterol (p=0.03), but not with very low density lipoprotein+LDL cholesterol, triglycerides, C-reactive protein and insulin (all p>0.20). The relationship between plasma PLTP activity and IMT was not significant in control subjects. Conclusions/interpretation Plasma PLTP activity is a positive determinant of IMT in type 2 diabetes mellitus, suggesting that high PLTP activity is involved in accelerated atherosclerosis in this disease.     

Carotid atheromatic plaque is commonly associated with hypopituitary men

Hypopituitarism increases the risks of many cardiovascular conditions and therefore, patients with this disease are more prone to cardiovascular disease. To our knowledge, there have been few studies on carotid artery plaque in male patients with hypopituitarism in assessing cardiovascular risks. The aim of this study was to specifically compare carotid artery plaque while examining other major cardiovascular risk factors between male patients with hypopituitarism and control subjects. Forty male patients aged 30–70 years with hypopituitarism and forty age, sex- matched control subjects were recruited at the Yonsei University Severance Hospital, Seoul, Korea. Carotid intima media thickness (IMT) and atheromatous plaque, anthropometry, lipid profile, and pituitary hormones were assessed. Atheromatous plaque in the carotid arteries was observed more frequently in patients with hypopituitarism than age- and sex-matched control subjects (59.5% vs. 2.5%, P < 0.01) without differences of carotid IMTs. Patients with hypopituitarism also exhibited higher waist circumference, waist to hip ratio, total cholesterol and LDL cholesterol than control subjects. In subgroup analysis in male patients with hypopituitarism including GH deficiency, lower testosterone levels were associated with higher waist circumference (r = 0.446, P = 0.033). In conclusion, hypopituitary males exhibit an increased incidence of carotid artery plaque without differences of carotid IMTs, central obesity and higher total cholesterol level. Lower testosterone levels were associated with central obesity- a strong component of a metabolic syndrome, and unsubstituted testosterone deficiency might be an important cardiovascular risk factor in patients with hypopituitarism.     

FTO gene variants are strongly associated with type 2 diabetes in South Asian Indians

Aims and hypothesis  Variants of the FTO (fat mass and obesity associated) gene are associated with obesity and type 2 diabetes in white Europeans, but these associations are not consistent in Asians. A recent study in Asian Indian Sikhs showed an association with type 2 diabetes that did not seem to be mediated through BMI. We studied the association of FTO variants with type 2 diabetes and measures of obesity in South Asian Indians in Pune. Methods  We genotyped, by sequencing, two single nucleotide polymorphisms, rs9939609 and rs7191344, in the FTO gene in 1,453 type 2 diabetes patients and 1,361 controls from Pune, Western India and a further 961 population-based individuals from Mysore, South India. Results  We observed a strong association of the minor allele A at rs9939609 with type 2 diabetes (OR per allele 1.26; 95% CI 1.13–1.40; p = 3 × 10⁻⁵). The variant was also associated with BMI but this association appeared to be weaker (0.06 SDs; 95% CI 0.01–0.10) than the previously reported effect in Europeans (0.10 SDs; 95% CI 0.09–0.12; heterogeneity p = 0.06). Unlike in the Europeans, the association with type 2 diabetes remained significant after adjusting for BMI (OR per allele for type 2 diabetes 1.21; 95% CI 1.06–1.37; p = 4.0 × 10⁻³), and also for waist circumference and other anthropometric variables. Conclusions  Our study replicates the strong association of FTO variants with type 2 diabetes and similar to the study in North Indians Sikhs, shows that this association may not be entirely mediated through BMI. This could imply underlying differences between Indians and Europeans in the mechanisms linking body size with type 2 diabetes. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users. C. S. Janipalli, S. Bhaskar, S. R. Kulkarni and R. M. Freathy contributed equally to this study.     

Effect of pioglitazone on insulin sensitivity,vascular function and cardiovascular inflammatory markers in insulin‐resistant non‐diabetic Asian Indians

Aims To determine the effects of pioglitazone (30 mg once daily for 16 weeks) on insulin sensitivity, insulin‐mediated vasodilation, vascular inflammatory markers, fat distribution and lipids in Asian Indians and Caucasians of European ancestry. Methods Cross‐sectional study. Eighteen non‐diabetic Asian Indians and 17 Caucasians of comparable age (34 ± 3 vs. 36 ± 3 years) and body mass index (26.0 ± 1.2 vs. 24.7 ± 1.0 kg/m²) had measurements of insulin sensitivity (M, insulin clamp at 6 pmol/kg per min), abdominal fat (computed tomographic scan at L4‐L5), endothelial‐dependent (reactive hyperaemia, RH) and ‐independent (0.4 mg sublingual nitroglycerin, TNG) vasodilation using brachial artery ultrasound before and after the 2‐h clamp at baseline and after pioglitazone therapy. Results Asian Indians were insulin resistant compared with Causasians during the baseline clamp (M = 25.6 ± 1.7 vs. 41.1 ± 2.2 µmol/kg per min, P < 0.0001) and improved significantly after pioglitazone (to 33.9 ± 1.7 µmol/kg per min, P < 0.001). Vasodilatory responses to RH and TNG were similar in Asian Indians and Caucasians at baseline and did not change. Insulin‐mediated vasodilation improved after pioglitazone in Asian Indians, but not in Caucasians, and correlated with the change in insulin sensitivity (r = 0.52, P = 0.03). C‐reactive protein (CRP) was higher in Asian Indians vs. Caucasians (1.6 ± 0.4 vs. 0.9 ± 0.2 mg/l) and was negatively correlated with insulin sensitivity (r = ?0.53, P = 0.02). In the Asian Indian group, CRP and plasminogen activator inhibitor‐1 decreased and adiponectin increased after pioglitazone, but there were no significant changes in total or visceral fat. Conclusions These results demonstrate that insulin‐resistant Asian Indians respond favourably to an insulin sensitizer with improvements in insulin sensitivity, cardiovascular and inflammatory risk markers, and vascular responses to insulin. These agents may have a role in decreasing the risk of diabetes and cardiovascular disease in this high‐risk population.     

Association of metabolic syndrome with carotid atherosclerosis in the young North Indian population

BackgroundMetabolic syndrome (MetS) and its components are associated with increased risk of stroke and cardiovascular disease. Relationship of MetS to carotid atherosclerosis has not been documented well in North Indian population.Aims(1) To determine the incidence of metabolic syndrome in asymptomatic healthy young North Indian population; (2) to evaluate individuals with MetS patients for carotid atherosclerosis by carotid duplex ultrasound examination; (3) to determine the significance of each component of MetS in relation to carotid atherosclerosis in these patients.Methods440 individuals in the age group of 25–50 years, asymptomatic for cardiac or cerebrovascular disease were screened for metabolic syndrome. 162 patients from a hospital-based population fulfilled the criteria for MetS (as per NCEP ATP III criteria). Duplex ultrasound (DU) examination of extracranial carotid vessels was performed on all the subjects. 112 age- and sex-matched controls were screened, and they underwent DU examination for comparison.ResultsHypertriglyceridemia was the commonest component seen in 79.6% of the MetS subjects, followed by central obesity seen in 74.6% subjects. Carotid atherosclerotic disease was observed in 21.6% of patients with MetS. Mild atherosclerosis (intima media thickness (IMT) >0.09 cm) was observed in 82.8% and 17.3% had plaques with mild stenosis (<50%) in the extracranial carotid arteries. Among patients of MetS with carotid atherosclerotic disease 82.6% had hypertriglyceridemia and 71.5% had 4 or more components for MetS. Among controls, five subjects (4.46%) had evidence of mild carotid atherosclerosis (IMT >0.09 cm) on DU. MetS was significantly associated with carotid DU abnormalities (increased IMT >0.09 cm) compared to controls (Fischer's exact test p < 0.0001). Univariate analysis showed the relationship of hypertriglyceridemia to carotid atherosclerosis (p = 0.03). On multivariate regression analysis none of the individual components of MetS contributed significantly to the presence of carotid atherosclerosis.ConclusionsMetS is common in asymptomatic healthy North Indian population, with hypertriglyceridemia being the commonest component of MetS in this population, which may be predictive of carotid atherosclerotic disease. Serum triglyceride estimation can serve as a screen for asymptomatic healthy subjects to select the target population for cerebrovascular disease prevention.     

Gender-specific differences in carotid intima-media thickness and its progression over three years: A multicenter European study

Background and aimsThis multicentre European study evaluated, in a young-to-middle-aged healthy population without carotid atherosclerosis, the gender-related differences in carotid intima-media thickness (IMT) and its short-term (3-year) progression, and whether these differences are related to different vascular ageing rate, cardiovascular risk profile or different susceptibility to family predisposition to cardiovascular diseases (CVD).Methods and results366 men and 422 women (age between 30 and 60 years) underwent B-mode carotid ultrasound at baseline and after 3-year follow-up period. IMT in 3 carotid segments was higher in men than in women (p < 0.0001 for all segments). When evaluated according to age decade, differences between men and women disappeared in the 6th decade, as in this decade a 3-year IMT progression rate accelerated in women (p < 0.05 as compared to the 4th and 5th age decade). Age was a major determinant of baseline all-segment IMT in women; in men all-segment IMT was influenced by age and LDL-cholesterol. IMT progression did not correlate with established cardiovascular risk factors, their short-term changes or family predisposition to CVD. Yet, a 3-year IMT progression in common carotid artery (CCA) was higher in men (p = 0.01) and women (p < 0.01) in whom relative Framingham risk increased during the corresponding period.ConclusionThis study provides reference values on IMT and its short-term progression in healthy young-to-middle-aged population, and demonstrates gender-related differences in the susceptibility of carotid wall to ageing and LDL-cholesterol. Increase in Framingham risk accelerated a short-term CCA IMT progression rate in both genders, whereas family predisposition to CVD did not influence carotid IMT.     

Serum immunoreactive insulin responses to a glucose load in Asian Indian and European Type 2 (non-insulin-dependent) diabetic patients and control subjects

Summary The serum immunoreactive insulin response to an oral glucose load was estimated in 15 Asian Indian and 29 European non-diabetic subjects, and in 45 Asian Indian and 72 European Type 2 (non-insulin-dependent) diabetic patients. In the non-diabetic group, basal insulin values were higher in the Asian Indians than the Europeans (16.7 ± 3.0 vs. 6.9 ± 0.7 mU/l, p < 0.001), and remained higher throughout the glucose tolerance test. Total insulin response was also higher in the Asian Indians (p < 0.001), and linear regression analysis revealed basal insulin, body mass index and race to be important predictors of insulin response. Amongst the diabetic patients, basal insulin values were again higher in the Asian Indians compared with the Europeans (18.0±5.0 vs. 11.5±0.9 mU/l, p<0.05). Total insulin response was also greater (p < 0.01). Linear regression analysis revealed the basal insulin value to be the only significant predictor of insulin response. The results demonstrate higher insulin levels in Asian Indians than Europeans in both normal subjects and Type 2 diabetic subjects. The insulin response to a glucose load is also greater in the Asian Indians. In the control subjects, ethnic differences contribute to this response, whereas in the diabetic patients this is a function of the elevated basal insulin values of the Asian Indians.     

Metabolic syndrome in patients with systemic lupus erythematosus from South India

ObjectivesTo find the prevalence of metabolic syndrome in systemic lupus erythematosus (SLE) compared to controls and to identify association of metabolic syndrome with SLE disease activity and damage.MethodsA total of 82 SLE and 82 healthy controls were studied. Metabolic syndrome was defined by National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III), consensus definition for Asian Indian Adults and World Health Organisation (WHO) 1999 definition, and associations with lupus characteristics, disease activity, and damage were examined. Insulin resistance (IR) was estimated using the homeostasis model assessment for IR (HOMA-IR).ResultsMetabolic syndrome was present in 24.39% SLE and 12.19% controls (p < 0.04) by NCEP ATP III criteria; 29.26% SLE and 19.51% controls (p = 0.14) by consensus definition for Asian Indians; 18.2% SLE and 7.31% controls (p < 0.035) by WHO 1999 criteria.Hypertension and hypertriglyceridemia were more frequent in SLE than in controls. Mean body mass index, diastolic and systolic blood pressure, triglycerides, and total cholesterol were higher in SLE than in controls. HOMA-IR (median, range) was 1.31 (0.06–9.32) and 1.55 (0.01–7.92), p = 0.09 in SLE and controls, respectively. There was no association of metabolic syndrome with disease activity/damage and prednisolone use. SLE patients with metabolic syndrome had a significantly longer duration of disease compared to patients without metabolic syndrome.ConclusionSouth Indian SLE patients have higher prevalence of NCEP ATP III and WHO defined metabolic syndrome compared to healthy controls. SLE patients have an altered lipid profile, but there was no IR and no association of metabolic syndrome with disease activity or damage.     

Associations of matrix metalloproteinase-9 and monocyte chemoattractant protein-1 concentrations with carotid atherosclerosis,based on measurements of plaque and intima–media thickness

Purpose

To examine associations of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-1 (MCP-1) concentrations with the severity of carotid atherosclerosis, based on measurements of carotid plaque and intima–media thickness (IMT).

Methods

This cross-sectional study included 116 stroke-free participants (45.7% males, 54.3% females; mean age, 64.73 ± 14.53 years). Serum MMP-9 and MCP-1 concentrations were measured, and plaque morphology, including total plaque score (PS), plaque stability, and IMT, was assessed ultrasonographically. Participants were grouped according to total PS (0, 1–2, ≥3), plaque stability (no plaque, stable, unstable) and IMT tertiles (<0.8 mm, 0.8–1 mm, >1 mm). Multinomial logistic regression models were used to assess the associations of MMP-9 and MCP-1 concentrations with plaque and IMT values after adjusting for vascular risk factors.

Results

MMP-9 quartiles (vs. quartile 1) were significantly associated with a greater prevalence of plaque instability [Q2: odds ratio (OR) = 5.13, 95% confidence interval (CI) = 1.01–24.9, p = 0.042; Q3: OR = 15.5, 95% CI = 3.1–78.1, p = 0.001; Q4: OR = 13.2, 95% CI = 2.7–64.97, p = 0.001] and high total PS (Q3: OR = 10.02, 95% CI = 1.5–65.33, p = 0.016; Q4: OR = 21.5, 95% CI = 3.5–132.1, p = 0.001). MCP-1 concentration was significantly associated with IMT (OR = 22.94, 95% CI = 2.14–245.66, p = 0.01).

Conclusions

Elevated serum MMP-9 concentration was independently associated with high total carotid artery PS, plaque instability, and large IMT value. MCP-1 concentration was independently associated with IMT, but not with plaque morphology.     

Carotid intima media thickness is increased and associated with morning cortisol in subjects with non-functioning adrenal incidentaloma

Data regarding cardiovascular risk in subjects with non-functioning adrenal adenoma are limited. The objectives of this study are to investigate carotid intima media thickness (IMT) as an indicator of atherosclerosis in subjects with non-functioning adrenal incidentaloma (AI) and to evaluate the factors that could be associated with IMT. Forty-nine subjects without findings of hypercortisolism or other adrenal gland disorders, 34 body mass index (BMI)-unmatched controls (C) and 18 BMI-matched controls (BC) were enrolled. Participants underwent hormonal evaluation including morning cortisol, adrenocorticotrophic hormone (ACTH), post dexamethasone suppression test cortisol (DST), dehydroepiandrosterone sulfate (DHEAS), and urinary free cortisol. Anthropometric and metabolic parameters and carotid IMT were measured. AI group had increased BMI, blood pressure, waist circumference, post DST cortisol, uric acid, and homeostasis model assessment (HOMA) levels when compared with C. Blood pressure, uric acid and, post DST cortisol remained significantly elevated in AI versus BC. Average IMT was increased significantly in AI versus C (0.74 mm vs. 0.68 mm, P = 0.029) and insignificantly elevated in AI versus BC (0.74 mm vs. 0.67 mm, P = 0.086). In all participants, IMT was correlated with age, BMI, HOMA, waist circumference, morning cortisol, and uric acid. Morning cortisol was independently associated with HOMA levels in both AI group and all participants. Increased IMT in non-functioning AI was a consequence of insulin resistant state associated with subtle cortisol autonomy rather than a direct effect of cortisol. The correlation between morning cortisol and IMT may be associated with the effect of hypothalamus–pituitary–adrenal axis disturbances on vasculature.     

Cardiovascular risk assessment and coronary artery calcification burden in asymptomatic patients in the initial years of hemodialysis

The specific tool for cardiovascular risk assessment in hemodialysis population has not yet been proposed, despite high prevalence of cardiovascular morbidity, and mortality in clinically asymptomatic patients. Coronary artery calcium score (CACS), as a reliable predictor of future cardiovascular events, might be a valuable approach. We sought to evaluate coronary artery calcification burden and its association with clinical and laboratory parameters in asymptomatic patients who recently initiated hemodialysis. The cross-sectional study included 60 asymptomatic patients receiving chronic hemodialysis for no longer than 48 months. CACS was assessed by cardiac computed tomography. Intima-media thickness (IMT) of both common carotid and femoral arteries were measured using ultrasonography. The mean total CACS was 160.50 (443). Patients' age correlated significantly with CACS (σ = 0.367; P = 0.004), carotid (σ = 0.375; P = 0.004) and femoral IMT (σ = 0.323; P = 0.013). Patients with CACS = 0 were significantly younger than patients with CACS >400: 52.4 ± 7.91 vs. 63.88 ± 8.37 years old, respectively (P = 0.034). In patients receiving dialysis for longer than 24 months CACS, femoral and carotid IMT were higher than in those dialyzed for less than 24 months; however, none has reached significance. There was a significant positive correlation between CACS and right (σ = 0.312; P = 0.018) and left (σ = 0.521; P < 0.001) femoral IMT, while not with carotid. CACS showed significant negative correlation with the serum iron (σ = ?0.351; P = 0.007). Calcification burden varies significantly in asymptomatic patients in early years of dialysis. It correlates with patients' age and tends to increase with dialysis vintage. Femoral IMT might be useful for cardiovascular risk stratification in asymptomatic patients who recently initiated hemodialysis.     

Ethnicity modifies the association between diabetes mellitus and ischaemic heart disease in Chinese, Malays and Asian Indians living in Singapore

Aims/hypothesis The aim of the study was to determine whether the risk of ischaemic heart disease (IHD) associated with diabetes mellitus differs between ethnic groups.Methods Registry linkage was used to identify IHD events in 5707 Chinese, Malay and Asian Indian participants from three cross-sectional studies conducted in Singapore between the years 1984 and 1995. The study provided a median of 10.2 years of follow-up with 240 IHD events experienced. We assessed the interaction between diabetes mellitus and ethnicity in relation to the risk of IHD events using Cox proportional hazards regression.Results Diabetes mellitus was more common in Asian Indians. Furthermore, diabetes mellitus was associated with a greater risk of IHD in Asian Indians. The hazard ratio when comparing diabetes mellitus with non-diabetes mellitus was 6.41 (95% CI 5.77–7.12) in Asian Indians and 3.07 (95% CI 1.86–5.06) in Chinese (p = 0.009 for interaction). Differences in the levels of established IHD risk factors among diabetics from the three ethnic groups did not appear to explain the differences in IHD risk.Conclusions/interpretation Asian Indians are more susceptible to the development of diabetes mellitus than Chinese and Malays. When Asian Indians do develop diabetes mellitus, the risk of IHD is higher than for Chinese and Malays. Consequently, the prevention of diabetes mellitus amongst this ethnic group is particularly important for the prevention of IHD in Asia, especially given the size of the population at risk. Elucidation of the reasons for these ethnic differences may help us understand the pathogenesis of IHD in those with diabetes mellitus.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorised users.     

Increased subclinical atherosclerosis in patients with chronic plaque psoriasis

Background: Psoriasis is an immune-mediated inflammatory skin condition of unknown aetiology which usually requires life-long treatment. It is regarded a systemic inflammatory disease with a possible increased risk of cardiovascular disease. The aim of this study was to assess carotid intima-media thickness (IMT), plaque prevalence and carotid stenosis as surrogate measures for cardiovascular disease in psoriasis patients and healthy controls. Methods: Sixty-two patients with psoriasis and thirty-one healthy controls were included in the study. All were examined by Colour duplex ultrasound of the carotid arteries to compare carotid IMT values, carotid plaques and carotid stenosis in the two groups. Adjustments were made for traditional cardiovascular risk factors. Results: Patients with psoriasis had increased carotid IMT values compared to the controls: mean ± SD 0.71 ± 0.17 mm vs. 0.59 ± 0.08 mm; p = 0.001. When adjusted for known atherosclerotic risk factors this difference remained significant (p = 0.04). Carotid plaques were also more common (p = 0.03) in patients with psoriasis 13 (21%) compared to controls 1 (3%). There was no difference with regard to the number of carotid stenoses in patients and controls. Conclusion: The results of this study support previous evidence which suggests that psoriasis is associated with an increased risk for atherosclerosis and subsequent cardiovascular disease.     

Inter-relationship between low-density lipoprotein phenotype and carotid intima-media thickness in North Indian type 2 diabetic subjects

AimsDiabetic dyslipidemia is characterized by a preponderance of small dense LDL which is highly atherogenic. The aim of this study was to examine the interrelationship between LDL Phenotype and atherosclerosis; to determine the factors determining LDL phenotype; and evaluate LDLc:apo-B ratio as a surrogate for the assessment of LDL phenotype in a group of North Indian Type 2 diabetic subjects.Methods285 diabetic subjects attending the outpatient Endocrine Clinic were subjected to detailed anthropometry and fasting serum lipid and apo-B was measured. The carotid intima-media thickness (IMT) was determined using a high resolution B-mode Ultrasonography. LDLc:apo-B ratio was taken as a surrogate index for LDL size.Results29.5% patients with normal triglyceride levels and 52.1% patients with normal LDLc levels showed the presence of small dense LDL or Phenotype B as estimated by the LDL cholesterol/apo-B ratio. The mean IMT in Phenotype B group was higher (0.88 mm vs. 0.68 mm). Triglycerides was the most important predictor variable predicting carotid IMT (R² = 0.15, β = 0.376) as well as LDL phenotype B (R² = 0.28, β = 0.561).ConclusionsTriglycerides and HDLc contribute independently to the variability in LDL particle size, and LDL particle size was associated with preclinical atherosclerosis as determined by carotid IMT in North Indian Type 2 diabetic subjects. LDL cholesterol/apo-B ratio serves as an easy clinical tool to determine the elevated small dense LDL.     

Impact of different Asian ethnic groups on correlation between heparin dose, activated clotting time and complications in percutaneous coronary intervention

The current recommended weight-adjusted dosing regimen of unfractionated heparin and target activated clotting time (ACT) in percutaneous coronary intervention (PCI) is based on limited data from the western population, and the applicability in the various Asian ethnic groups remains unknown. This is a retrospective study in an Asian university teaching hospital. Among the 1287 patients who have undergone PCI, Chinese constituted 70.4% (n = 906), Malay 15.5% (n = 199) and Indian 14.1% (n = 182). Overall, the mean total heparin dose was 6224 ± 1548 U, mean weight-adjusted heparin dose was 95 ± 30 U/kg, and mean ACT was 325 ± 95 s. There was no significant difference in the 3 ethnic groups. Both the incidences of in-hospital ischemic complications (Chinese 2.4%, Malay 3.5%, Indian 2.2%, p = 0.641) as well as in-hospital bleeding complications (Chinese 4.5%, Malay 3.5%, Indian 6.0%, p = 0.490) were similar in the 3 ethnic groups. When the patients were divided based on ACT into 3 groups:< 250, 250–350 and> 350 seconds, the incidence of ischemic complication (2.5%, 2.5%, 2.7%) was similar (p = 819), while that of bleeding complications (4.1%, 3.5%, 6.8%) showed a strong trend (p = 0.057) of increased risk in patients with ACT > 350 s. In conclusion, the recommended weight-adjusted heparin-dosing regimen in PCI derived from the western population is equally applicable to the Asian patients. ACT does not correlate with in-hospital ischemic complications, but increased bleeding complications were observed with ACT > 350 s.     

The impact of serum uric acid level on arterial stiffness and carotid atherosclerosis: The Korean Multi-Rural Communities Cohort study

Objective

Serum uric acid level has been found to be associated with a risk factor for cardiovascular diseases. However, the topic has not been explored in the general population, especially in Korea. This study was designed to determine whether serum uric acid is associated with carotid atherosclerosis and arterial stiffness in the Korean Multi-Rural Communities Cohort study.

Methods

A total of 5568 participants from the Korean Multi-Rural Communities Cohort were evaluated for the risk of hyperuricemia in cardiovascular atherosclerosis. Important surrogates for cardiovascular atherosclerosis such as intima–media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were assessed. We evaluated the association between these atherosclerosis indices and serum uric acid level or hyperuricemia through multivariate-adjusted logistic and linear regression analyses.

Results

There was a significant difference of carotid IMT and baPWV between males and females (p < 0.0001, respectively). Both male and female subjects with hyperuricemia showed higher baPWV than subjects without hyperuricemia (p = 0.0004 for males; p = 0.001 for females). Serum uric acid level was positively correlated with baPWV in males (β = 0.0006, p < 0.0001) and in females (β = 0.0001, p = 0.04), whereas no association between serum uric acid and carotid IMT was found in either gender. A linear relationship of baPWV with increasing serum uric acid level was observed in males (p = 0.0005) and in females (p = 0.004).

Conclusion

Serum uric acid level could be considered an important risk factor for arterial stiffness in Korean population, whereas carotid IMT is not associated with serum uric acid in either gender when using data from the Korean Multi-Rural Communities Cohort study.     

Positive correlation between malondialdehyde-modified low-density lipoprotein cholesterol and vascular inflammation evaluated by F-FDG PET/CT

Objective: The purpose of this study was to investigate the relationship between serum levels of malondialdehyde-modified low-density lipoprotein cholesterol (MDA-LDL) and vascular inflammation evaluated by fluorine-18 fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT). Methods/results: The study involved 106 consecutive patients (75 males and 31 female, mean age 62.5 ± 7.7 years) who visited our hospital for cardiovascular risk screening and underwent carotid ultrasonography, ¹⁸F-FDG PET/CT, complete history, physical examinations, and determination of blood chemistry including high-sensitivity C-reactive protein (hsCRP), asymmetric dimethylarginine (ADMA), and MDA-LDL. Vascular inflammation, was measured as blood-normalized standardized ¹⁸F-FDG uptake value, known as the target-to-background ratio (TBR) of carotid arteries. Univariate and multiple stepwise regression analyses were performed for determining independent correlates of carotid TBR values. Median MDA-LDL, mean carotid TBR values and carotid intima-media thickness (IMT) were 127.5 (IQR 92.0–147.8) U/l, 1.55 ± 0.22, and 0.72 ± 0.15 mm, respectively. Univariate analysis revealed that carotid TBR values positively correlated with MDA-LDL (p = 0.043) and carotid IMT (p = 0.049). Multiple stepwise regression analysis demonstrated that MDA-LDL (p = 0.043) and carotid IMT (p = 0.038) were independently associated with carotid TBR values. Conclusion: The present study reveals that serum levels of MDA-LDL are independently associated with vascular inflammation evaluated by ¹⁸F-FDG PET/CT. Circulating MDA-LDL may be a more useful clinical biomarker for vascular inflammation within the atherosclerotic plaques than hsCRP or ADMA.