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Abstract Background Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD). Calcium channel genes (CCG) contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS) data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis. Methods A total of 2,176 single-nucleotide polymorphisms (SNP) (703 genotyped and 1,473 imputed) covering the genes that encode the α1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE) and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP). SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel. Results Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations. Conclusions These associations support a role for common CCG SNPs in ASD.

Objective: To evaluate whether glycation of high-density lipoprotein (HDL) increases cardiovascular risk in patients with type 2 diabetes mellitus by altering its anti-atherogenic property., Data Sources: Data cited in this review were obtained mainly from Pubmed and Medline in English from 2000 to 2013, with keywords "glycation", "HDL", and "atherosclerosis". Study selection Articles regarding glycation of HDL and its role in atherogenesis in both humans and experimental animal models were identified, retrieved and reviewed., Results: Glycation alters the structure of HDL and its associated enzymes, resulting in an impairment of atheroprotective functionality and increased risks for cardiovascular events in type 2 diabetic patients., Conclusion: Glycation of HDL exerts a deleterious effect on the development of cardiovascular complications in diabetes.

Background: Weight gain following smoking cessation increases cardiovascular risk, but its effects on prognosis after percutaneous coronary intervention (PCI) remain unclear. This study aimed to investigate the relationship between weight gain post smoking cessation and one-year clinical outcome in patients who underwent PCI with drug-eluting stent (DES)., Methods: A total of 895 consecutive male smoking patients were divided into quitters (n = 437) and continuers (n = 458) according to their smoking status after PCI. Weight gain, major adverse cardiac events (MACE, including cardiac deaths, myocardial infarction and revascularization), and recurrent angina were recorded during follow-up for one year., Results: Average weight gain in quitters was more than that in continuers (1.5 kg vs. -0.03 kg, P < 0.001). Weight was unchanged or increased by more than 1.5 kg in 78.17% of continuers, while 50.57% of quitters had a weight gain of less than 1.5 kg. Compared with continuers, MACE in quitters was significantly reduced after PCI (6.12% vs. 4.81%, P = 0.049), especially recurrent angina (13.97% in continuers vs. 9.84% in quitters, P = 0.027). After adjusting for weight gain and other factors, smoking cessation was independently associated with a lower risk of MACE and recurrent angina (OR = 0.73, P = 0.035). However, weight gain > 1.5 kg (OR = 1.55, P = 0.026) could curtail the benefits from smoking cessation., Conclusions: Weight gain may reduce the benefits of smoking cessation after PCI with DES implantation. Thus, although smoking cessation is recommended after PCI, weight control should also be highly encouraged for these patients.

Objective: To investigate the relationship between smoking and insulin resistance in non-obese male patients with CAD., Methods: 414 consecutive non-obese male patients with angiographically-documented CAD (luminal diameter narrowing > 50%) were recruited, including 113 nonsmokers and 301 smokers. With 99 mild smokers (< 400 packs/year), 95 medium smokers (400 - 799 packs/year) and 107 heavy smokers (≥ 800 packs/year). Insulin resistance index (IRI) was expressed by homeostasis model assessment for insulin resistance (HOMA-IR) calculated by the formula of [fasting serum glucose (mmol/L) × fasting plasma insulin (mU/L)]/22.5. IRI ≥ 2.69 was defined as insulin resistance, while IRI < 2.69 was insulin sensitive. Fasting glucose, fasting insulin and IRI were recorded and odds ratio for the incidence of insulin resistance was calculated., Results: Fasting glucose was higher in heavy smokers (5.86 mmol/L) than that in nonsmokers (5.51 mmol/L, P = 0.037) and mild smokers (5.33 mmol/L, P = 0.014). Fasting insulin and IRI were also significantly higher in heavy smokers (10.25 mU/L) than those in non-smokers (8.72 mU/L, P = 0.0231, respectively) and mild smokers (8.67 mU/L, P = 0.0231). Compared with nonsmokers, the odds ratio for the incidence of insulin resistance was 1.53 (95%CI 0.55 - 2.94; P = 0.027) in medium smokers and 1.89 (95%CI 0.49 - 3.14; P = 0.018) in heavy smokers., Conclusions: The relationship between smoking and insulin resistance is highly dose dependent in non-obese male patients with CAD.

Background: Insulin resistance (IR) is significantly associated with coronary artery disease and cardiovascular events in patients with or without type 2 diabetes mellitus. This study aimed to evaluate the influence of IR on long-term outcomes of patients undergoing percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) implantation., Methods: A total of 467 consecutive patients undergoing SES-based PCI were divided into IR group (n = 104) and non-IR group (n = 363). The patients were followed up for one year. The rate of major adverse cardiac events (MACEs) including death, non-fatal myocardial infarction and recurrent angina pectoris was compared by the log-rank test, and the independent risk factors were identified by the Cox regression analysis., Results: MACEs occurred more frequently, and cumulative survival rate was lower in the IR group than in the non-IR group during the follow-up (all P < 0.05). IR was an independent risk factor for the occurrence of cardiac death and non-fatal myocardial infarction (OR = 2.76, 95%CI = 1.35 - 5.47, P = 0.034). Old age, diabetes, and multi-vessel disease were determinants for recurrent angina pectoris after PCI (P < 0.05). Subgroup analysis revealed that IR (OR = 3.35, 95%CI = 1.07 - 13.59, P = 0.013) and multi-vessel disease (OR = 2.19, 95%CI = 1.01 - 5.14, P = 0.044) were independent risk predictors for recurrent angina pectoris in patients with diabetes after PCI., Conclusions: IR is associated with reduced MACE-free survival and remains an independent predictor for recurrent angina pectoris after PCI with SES implantation.

Background: It is well known that diabetes mellitus (DM) is a crucial risk factor for coronary artery disease (CAD). The present study aimed to investigate angiographic profiles of the coronary arteries in diabetic CAD patients in comparison with nondiabetics., Methods: A total of 546 Chinese patients were angiographically documented for CAD, 375 of whom were diabetics and 171 were nondiabetics according to the WHO diabetes criteria (1999). The patients in these two groups were matched for age, sex, and body mass index (BMI). The 75 g oral glucose tolerance test (OGTT) was performed in all patients, for whom blood glucose, insulin, glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A (ApoA), apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)] were measured. Insulin resistance (Homa-IR) and insulin secretion index (Homa-IS) were determined by the HOMA model. The clinical features and the data from selective coronary angiographies were compared between the diabetic and nondiabetic CAD patients., Results: Diabetic CAD patients had significantly higher waist to hip ratio (WHR) (p=0.016), fasting plasma glucose (FPG), 2h plasma glucose (2hPG), glycosylated hemoglobin (HbA1c) (p<0.001), insulin resistance index (Homa-IR) (p=0.001), and apolipoprotein A (ApoA) (p=0.008), with a significantly lower insulin secretion index (Homa-IS) level (p<0.001). Diabetic patients had one-vessel disease less frequently (28.8% vs 46.2%, p<0.001), and three-vessel disease more frequently (35.2% vs 24.0%, p=0.009), and they also had significantly higher cumulative coronary atherosclerosis score (CAS) (p=0.003). The right coronary artery was significantly more frequently involved in diabetics (66.4% vs 52.6%, p=0.002), with a clearly higher CAS at the same time (p=0.002)., Conclusions: Diabetics were presented with more severe and diffuse angiographically documented coronary artery disease compared to nondiabetics. The right coronary artery was significantly more frequently involved in the diabetics. Duration of CAD, Homa-IR, and diabetes mellitus were the independent risk factors for CAD found in the present study, while ApoA was the protective one.

Objective: The impact of late incomplete stent apposition (ISA) post sirolimus eluting stent (SES) implantation in patients with acute coronary syndrome (ACS) on long-term clinical outcomes remains controversial. The aim of the present study was to evaluate the association between late ISA and clinical outcomes in patients with ACS compared with that with stable angina (SA)., Methods: From February 2005 to March 2007, 54 ACS patients and 83 SA patients were enrolled in this study, late ISA was determined by means of three-dimensional volumetric intravascular ultrasound (IVUS) analyses one year after SES implantation and clinical outcomes one year post IVUS were obtained in these patients., Results: In 219 treated lesions of the 137 patients, late ISA was documented in 25 lesions in 16 patients (20 ISA in 12 ACS patients vs. 5 ISA in 4 SA patients, P<0.001). Though lumen area in reference and stented segment, neointimal hyperplasia (NIH) area and percentage of NIH in stented segment, and external elastic membrane (EEM) area in reference segment were similar between two groups, EEM area in stented segment [(15.34+/-5.44) mm2 vs. (13.83+/-4.51) mm2, P=0.026], stented/reference segment EEM area ratio (1.13+/-0.22 vs. 1.02+/-0.18, P<0.001), plaque and media area [(8.43+/-3.93) mm2 vs. (7.01+/-2.93) mm2, P=0.002] was significantly lager in ACS group than that in SA group. Multivariable logistic analysis showed that ACS (OR 6.477 with 95% CI from 2.297 to 18.263, P<0.001) and stent length>or=23 mm (OR 3.680 with 95% CI from 1.181 to 11.469, P=0.025) were main independent factors of occurrence of late ISA. Incidence of main adverse cardiac events (MACE) one year post IVUS was similar between the two groups., Conclusion: Compared with patients with SA, ACS patients had larger stented segment EEM area, plaque and media area as well as increased incidence of ISA. However, the incidence of MACE was similar in ACS and SA patients one year after IVUS.

Background: Late incomplete stent apposition (ISA) may occur after drug-eluting stent implantation, affecting long-term clinical outcomes. This study aimed to evaluate the impact of clinical presentations of coronary artery disease on late ISA after percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) by means of three-dimensional volumetric intravascular ultrasound (IVUS) analyses., Methods: One hundred and thirty-seven patients with coronary artery disease received SES implantation during PCI and had repeat angiography with IVUS examination. All patients were followed up one year after the procedure., Results: In overall 219 treated lesions (137 patients), late ISA was identified in 25 lesions (16 patients). Clinical diagnosis of acute coronary syndrome (ACS) and use of long stents were more common in patients with than in those without late ISA. Patients with late ISA had greater external elastic membrane (EEM) area in stented segment ((15.34 +/- 5.44) vs (13.83 +/- 4.51) mm(2), P = 0.026), stented-to-reference segment EEM area ratio (1.13 +/- 0.22 vs 1.02 +/- 0.18, P < 0.001), and plaque and media area ((8.43 +/- 3.93) vs (7.01 +/- 2.93) mm(2), P = 0.002) than in those without late ISA. Multivariate Logistic regression analysis showed that clinical diagnosis of ACS and use of long stents were independent risk factors for late ISA (OR 6.477, 95% CI 2.297 - 18.263, P < 0.001; OR 3.680, 95% CI 1.181 - 11.469, P = 0.025; respectively). During one-year follow-up after IVUS examination, the rate of very late stent thrombosis tended to be higher in patients with than in those without late ISA (18.7% vs 3.3%, P = 0.051)., Conclusions: The occurrence of late ISA after SES implantation may be related to clinical status, use of long stents, and marked positive vessel remodeling. Late ISA tended to increase the rate of very late stent thrombosis during follow-up, highlighting the importance of long-term dual antiplatelet therapy for these patients.

Background: Serum high sensitive C-reactive protein (hs-CRP), adiponectin levels and urine albumin excretion rate (UAER) are probably associated with inflammation and atherosclerosis. The aim of this study was to determine the three markers in coronary artery disease (CAD) subjects with different glucose tolerance status in a Chinese population and further explore the levels of the three markers in these subjects and the possible association of these markers with CAD risk factors and the severity of CAD as well., Methods: A total of 242 subjects with angiographically documented CAD were recruited, and then assigned to three groups: the normal glucose tolerance (NGT) + CAD group, including 100 CAD patients with NGT; the impaired glucose tolerance (IGT) + CAD group, 40 CAD patients with IGT; the type 2 diabetes mellitus (T2DM) + CAD group, 102 CAD patients with T2DM. Serum hs-CRP, adiponectin levels as well as UAER were measured in all subjects., Results: Serum hs-CRP levels were increased in the T2DM + CAD group compared with the NGT + CAD group (4.71 +/- 2.59) vs (3.60 +/- 2.46) mg/L, P = 0.037. Serum adiponectin levels were gradually decreased from the NGT + CAD to IGT + CAD to T2DM + CAD groups, (5.99 +/- 1.84), (5.82 +/- 1.72) and (4.65 +/- 1.71) mg/L, P = 0.002 and 0.040 for NGT + CAD and IGT + CAD groups vs T2DM + CAD group, respectively. While the UAER was gradually increased from the NGT + CAD to IGT + CAD to T2DM + CAD groups, (6.42 +/- 2.51), (6.89 +/- 2.94) and (15.03 +/- 4.22) microg/min (P < 0.001) for NGT + CAD and IGT + CAD groups vs T2DM + CAD group. Multiple linear stepwise regression analysis showed that waist-hip ratio (WHR) and low density lipoprotein cholesterol (LDL-C) were the significant determinants of serum hs-CRP levels; triglyceride (TG), high density lipoprotein cholesterol (HDL-C), age, WHR, T2DM, 2-hour serum insulin (2hINS), sex, and apolipoprotein B were the significant determinants of serum adiponectin levels; and systolic blood pressure (SBP), T2DM, and hemoglobin A1c (HbA1c) were the significant determinants of UAER in all subjects (R(2) = 0.070, 0.352, and 0.214, respectively). However, no significant correlation was seen for hs-CRP, adiponectin and UAER with the severity of CAD. Hs-CRP levels were significantly correlated with UAER., Conclusions: There was a trend of increased serum hs-CRP levels from the NGT + CAD to IGT + CAD to T2DM + CAD groups, though it only showed significance in the T2DM + CAD group compared with the NGT + CAD group. Serum adiponectin levels were decreased and UAER was increased from the NGT + CAD to IGT + CAD to T2DM + CAD groups. Increased UAER and serum hs-CRP, and decreased adiponectin levels were associated with traditional CAD risk factors but failed to be correlated with the severity of CAD. Hs-CRP levels were significantly correlated with UAER.

Background: Large animal models with toxin-mediated pancreatic damage have been used extensively in researches with respect to diabetes mellitus and cardiovascular diabetic complications. The present study aimed to establish Chinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and characterize the animal models by analyzing inflammatory cytokine levels in aortic wall, such as tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta) and interleukin-6 (IL-6)., Methods: Twenty-two male Chinese Guizhou minipigs (age, 4 to 6 months; weight, 20 kg to 30 kg) were divided into STZ-induced diabetic group (n = 12) and control group (n = 10). STZ (125 mg/kg) was administrated to induce hyperglycemia and afterwards insulin was used to control fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test (OGTT) was performed before and one month after STZ administration and serum concentrations of alanine transaminase, asparagine transaminase, albumin, blood urea nitrogen, creatinine, lipids and white blood cell count were measured before and six months later. Animals in both groups were euthanized after six months and pancreas was examined immunohistochemically for islet beta cells. Aortic intima of diabetic minipigs and controls was analyzed for TNF-alpha level in tissue conditioned medium by Western blot. TNF-alpha, IL-1beta and IL-6 mRNA levels in aortic intima were assayed by reverse transcription and polymerase chain reaction (RT-PCR)., Results: Significant elevation in serum glucose levels was observed one month and six months after STZ induction (P < 0.001) and markedly increased OGTT values were noted, compared with baseline data. The normal pancreas had many irregular sized islets and small clusters of islet beta cells, while in pancreas of diabetic minipigs islet beta cells almost disappeared. No statistical difference was notified in serum concentrations of biochemical examinations before and six months after STZ induction. Western blot demonstrated dramatically increased TNF-alpha level in aotic intima conditioned medium, and significant elevation of TNF-alpha, IL-1beta and IL-6 mRNA levels was revealed by RT-PCR., Conclusions: The present study has established Chinese Guizhou minipig models with STZ-induced diabetes. Inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) significantly elevated in aortic intima of diabetic minipigs.

Background: Patients with end-stage renal disease have a high mortality from coronary artery disease, but the impact of moderate renal insufficiency on clinical outcomes after percutaneous coronary intervention (PCI) and the effect of drug-eluting stent implantation in these patients remain unclear. This study determined the long-term effect of moderate renal insufficiency on death and major adverse cardiac events (MACE) after stent based PCI and examined whether drug-eluting stent implantation could favourably influence clinical outcome., Methods: Major adverse cardiac events and causes of mortality were determined for 1012 patients undergoing percutaneous intervention from January 1, 2002 to December 31, 2004 at Shanghai Ruijin Hospital. Based on estimated creatinine clearance levels, long term outcomes were compared between patients with estimated creatinine clearance < 60 ml/min (renal insufficiency group; n = 410) and those with estimated creatinine clearance > or = 60 ml/min (control group; n = 602). Subgroup analysis was also made for patients with renal insufficiency between drug eluting stent (n = 264) and bare metal stent implantation (n = 146) during PCI., Results: During follow-up (average 17 months) after successful PCI, all causes of death (7.1% vs 2.3%, P < 0.01) and cardiac death (3.4% vs 1.0%, all P < 0.01) were significantly higher in renal insufficiency group than in control group. For patients with moderate renal insufficiency, drug-eluting stent implantation reduced significantly all causes of death (5.3% vs 10.9%, P < 0.05) and occurrence of major cardiac adverse events (15.1% vs 24.6%, P < 0.05) compared with bare metal stents., Conclusions: Moderate renal insufficiency is an important clinical factor influencing the mortality after PCI in patients with coronary artery disease and the use of drug-eluting stents should be the preferred therapy for the improvement of long-term outcomes in such patients.