Baseline and follow-up assessment of regional left ventricular volume using 3-dimensional echocardiography: comparison with cardiac magnetic resonance

Background

2-D Echo is often performed in patients without history of coronary artery disease (CAD). We sought to determine echo features predictive of CAD.

Methods

2-D Echo of 328 patients without known CAD performed within one year prior to stress myocardial SPECT and angiography were reviewed. Echo features examined were left ventricular and atrial enlargement, LV hypertrophy, wall motion abnormality (WMA), LV ejection fraction (EF) < 50%, mitral annular calcification (MAC) and aortic sclerosis/stenosis (AS). High risk myocardial perfusion abnormality (MPA) was defined as >15% LV perfusion defect or multivessel distribution. Severe coronary artery stenosis (CAS) was defined as left main, 3 VD or 2VD involving proximal LAD.

Results

The mean age was 62 ± 13 years, 59% men, 29% diabetic (DM) and 148 (45%) had > 2 risk factors. Pharmacologic stress was performed in 109 patients (33%). MPA was present in 200 pts (60%) of which, 137 were high risk. CAS was present in 166 pts (51%), 75 were severe. Of 87 patients with WMA, 83% had MPA and 78% had CAS. Multivariate analysis identified age >65, male, inability to exercise, DM, WMA, MAC and AS as independent predictors of MPA and CAS. Independent predictors of high risk MPA and severe CAS were age, DM, inability to exercise and WMA. 2-D echo findings offered incremental value over clinical information in predicting CAD by angiography. (Chi square: 360 vs. 320 p = 0.02).

Conclusion

2-D Echo was valuable in predicting presence of physiological and anatomical CAD in addition to clinical information.     

Comparaison des taux de BNP et NT-proBNP chez des patients insuffisants rénaux pour prévenir l’insuffisance cardiaque

Background

The aim of the study was to compare the performances of BNP and NT-proBNP for diagnosing heart failure (HF) in a population of patients with high incidence of chronic renal insufficiency (CRI, plasma creatinine > 1.5 mg/dl).

Patients and methods

Ninety-eight patients were included in this study. BNP and NT-proBNP determinations were performed by an immunofluorescent assay (Biosite®) and by an electrochemiluminescence sandwich immuno assay (Roche Diagnostic®), respectively.

Results and discussion

BNP and NTproBNP level are correlated in CRI and non CRI. Both assays are useful to rule out CRI pts suspected of HF. However, in renal failure pts, higher decision limits should be used for improving the positive predictive value of the assays.     

The association of metabolic syndrome and Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus type 1: The Persian Gulf Healthy Heart Study

Background

Coronary artery disease is the leading cause of death in industrialized countries and most patients with diabetes die from complications of atherosclerosis. The objective of this study was to determine the presence of diabetes mellitus and other conventional coronary heart disease risk factors (cigarette smoking, hypertension and hyperlipidemia) in patients with acute coronary events in an Iranian population.

Methods

The study included 514 patients with unstable angina or myocardial infarction (MI) out of 720 patients admitted to CCU ward of a general hospital from March 2003 to March 2005. History of diabetes, hypertension and cigarette smoking, demographic indices, coronary heart disease and diabetes mellitus treatment, myocardial enzymes, serum triglycerides (TG) and cholesterol and fasting and non fasting blood glucose levels and HbA1C of diabetics were recorded of admission sheets. The data were structured to appropriate one way ANOVA, T tests, and chi square test with SPSS 13 product for windows.

Results

Out of all patients 35.8% were female, 30% were diabetics (Duration 13.4 ± 8.7 years), 42% were smoker and 91% were hypertensive. Twenty four percent had MI and 76% had unstable angina. MI was significantly higher in diabetic patients (36.4% vs. 19.2%, P < 0.001). Location and extension of MI and myocardial enzymes did not differ between diabetics and non-diabetic patients. Diabetic patients were older than non diabetics (65 ± 11.6 vs. 59.7 ± 12.5 years, p < 0.05). Five (66.7%) out of 9 patients with fatal MI were diabetics (Odds Ratio = 2.98). Age, duration of diabetes and HbA1c levels, did not differ between diabetic patients with or without MI. Hypertension and current smoking was significantly higher in patients with MI compared to patients with unstable angina (p < 0.05). Serum TG, HDL-C, LDL-C and total cholesterol level did not differ between patients with MI and unstable angina. Diabetic patients compare to non diabetic patients were more hypertensive (96% vs. 88.7%, p < 0.005) and had higher serum triglyceride (TG over 200 mg/dl, 35.1% vs. 26.4, p <0.05). Diabetes was more frequent among women than men (36.4% vs. 26.4%, p < 0.05). Women were older than men (65 ± 11.6 vs. 59.2 ± 13 years, p < 0.005) and had higher total serum cholesterol (200 ± 41.8 vs. 192 ± 42.5 mg/dl, p < 0.05) and HDL-C levels (49.7 ± 22 vs. 40 ± 13 mg/dl, p < 0.005). Ninety seven percent of all patients had at least one of cardiovascular risk factors (hypertension, smoking, diabetes, high cholesterol and low HDL-cholesterol levels).

Conclusion

In this study 19 out of 20 patients with acute coronary event have at least one of conventional cardiac risk factors. Diabetes and hypertension are leading risk factors, which may directly or indirectly interfere and predict more serious complications of coronary heart disease.     

Determinants of persistence in hypertensive patients treated with irbesartan: results of a postmarketing survey

Background

Persistence is a key factor for long-term blood pressure control, which is of high prognostic importance for patients at increased cardiovascular risk. Here we present the results of a post-marketing survey including 4769 hypertensive patients treated with irbesartan in 886 general practices in Switzerland. The goal of this survey was to evaluate the tolerance and the blood pressure lowering effect of irbesartan as well as the factors affecting persistence in a large unselected population.

Methods

Prospective observational survey conducted in general practices in all regions of Switzerland. Previously untreated and uncontrolled pre-treated patients were started with a daily dose of 150 mg irbesartan and followed up to 6 months.

Results

After an observation time slightly exceeding 4 months, the average reduction in systolic and diastolic blood pressure was 20 (95% confidence interval (CI) -19.6 to -20.7 mmHg) and 12 mmHg (95% CI -11.4 to -12.1 mmHg), respectively. At this time, 26% of patients had a blood pressure < 140/90 mmHg and 60% had a diastolic blood pressure < 90 mmHg. The drug was well tolerated with an incidence of adverse events (dizziness, headaches,...) of 8.0%. In this survey more than 80% of patients were still on irbesartan at 4 month. The most important factors predictive of persistence were the tolerability profile and the ability to achieve a blood pressure target ≤ 140/90 mmHg before visit 2. Patients who switched from a fixed combination treatment tended to discontinue irbesartan more often whereas those who abandoned the previous treatment because of cough (a class side effect of ACE-Inhibitors) were more persistent with irbesartan.

Conclusion

The results of this survey confirm that irbesartan is effective, well tolerated and well accepted by patients, as indicated by the good persistence. This post-marketing survey also emphasizes the importance of the tolerability profile and of achieving an early control of blood pressure as positive predictors of persistence.     

Efficacy and safety of moxifloxacin in acute exacerbations of chronic bronchitis: a prospective, multicenter, observational study (AVANTI)

Background

Acute exacerbations of chronic bronchitis (AECB), including chronic obstructive pulmonary disease (AECOPD), represent a substantial patient burden. Few data exist on outpatient antibiotic management for AECB/AECOPD in Eastern/South Eastern Europe, in particular on the use of moxifloxacin (Avelox®), although moxifloxacin is widely approved in this region based on evidence from international clinical studies.

Methods

AVANTI (AVelox® in Acute Exacerbations of chroNic bronchiTIs) was a prospective, observational study conducted in eight Eastern European countries in patients?>?35 years with AECB/AECOPD to whom moxifloxacin was prescribed. In addition to safety and efficacy outcomes, data on risk factors and the impact of exacerbation on daily life were collected.

Results

In the efficacy population (N?=?2536), chronic bronchitis had been prevalent for?>?10 years in 31.4% of patients and 66.0% of patients had concomitant COPD. Almost half the patients had never smoked, in contrast to data from Western Europe and the USA, where only one-quarter of COPD patients are non-smokers. The mean number of exacerbations in the last 12 months was 2.7 and 26.3% of patients had been hospitalized at least once for exacerbation. Physician compliance with the recommended moxifloxacin dose (400 mg once daily) was 99.6%. The mean duration of moxifloxacin therapy for the current exacerbation (Anthonisen type I or II in 83.1%; predominantly type I) was 6.4?±?1.9 days. Symptom improvement was reported after a mean of 3.4?±?1.4 days. After 5 days, 93.2% of patients reported improvement and, in total, 93.5% of patients were symptom-free after 10 days. In the safety population (N?=?2672), 57 (2.3%) patients had treatment-emergent adverse events (TEAEs) and 4 (0.15%) had serious TEAEs; no deaths occurred. These results are in line with the known safety profile of moxifloxacin.

Conclusions

A significant number of patients in this observational study had risk factors for poor outcome, justifying use of moxifloxacin. The safety profile of moxifloxacin and its value as an antibiotic treatment were confirmed. Physicians complied with the recommended 400 mg once-daily dose in a large proportion of patients, confirming the advantages of this simple dosing regimen.

Trial registration

ClinicalTrials.gov identifier: NCT00846911     

Insulin resistance in Chinese patients with type 2 diabetes is associated with C-reactive protein independent of abdominal obesity

Background

Patients with diabetes mellitus (DM) have high risk of heart failure. Whether some of the risk is directly linked to metabolic derangements in the myocardium or whether the risk is primarily caused by coronary artery disease (CAD) and hypertension is incompletely understood. Echocardiographic tissue Doppler imaging was therefore performed in DM patients without significant CAD to examine whether DM per se influenced cardiac function.

Methods

Patients with a left ventricular (LV) ejection fraction (EF) > 35% and without significant CAD, prior myocardial infarction, cardiac pacemaker, atrial fibrillation, or significant valve disease were identified from a tertiary invasive center register. DM patients were matched with controls on age, gender and presence of hypertension.

Results

In total 31 patients with diabetes and 31 controls were included. Mean age was 58 ± 12 years, mean LVEF was 51 ± 7%, and 48% were women. No significant differences were found in LVEF, left atrial end systolic volume, or left ventricular dimensions. The global longitudinal strain was significantly reduced in patients with DM (15.9 ± 2.9 vs. 17.7 ± 2.9, p = 0.03), as were peak longitudinal systolic (S') and early diastolic (E') velocities (5.7 ± 1.1 vs. 6.4 ± 1.1 cm/s, p = 0.02 and 6.1 ± 1.7 vs. 7.7 ± 2.0 cm/s, p = 0.002). In multivariable regression analyses, DM remained significantly associated with impairments of S' and E', respectively.

Conclusion

In patients without significant CAD, DM is associated with an impaired systolic longitudinal LV function and global diastolic dysfunction. These abnormalities are likely to be markers of adverse prognosis.     

Incidence of first ever stroke during Hajj ceremony

Background

The Hajj Ceremony, the largest annual gathering in the world, is the most important life event for any Muslim. This study was designed to evaluate the incidence of stroke among Iranian pilgrims during the Hajj ceremony.

Methods

We ascertained all cases of stroke occurring in a population of 92,974 Iranian pilgrims between November 27, 2007 and January 12, 2008. Incidence and risk factors of the first ever stroke in Hajj pilgrims were compared, within the same time frame, to those of the Mashhad residents, the second largest city in Iran. Data for the latter group were extracted from the Mashhad Stroke Incidence Study (MSIS) database.

Results

During the study period, 17 first-ever strokes occurred in the Hajj pilgrims and 40 first-ever stroke strokes occurred in the MSIS group. Overall, the adjusted incidence rate of first ever stroke in the Hajj cohort was lower than that of the MSIS population (9 vs. 16 per 100,000). For age- and gender-specific subgroups, the Hajj stroke crude rates were in general similar to or lower than the general population of Mashhad, Iran, with the exception of women aged 35 to 44 years and aged >75 years who were at greater risk of having first-ever stroke than the non-pilgrims of the same age.

Conclusion

The first ever stroke rate among Iranian Hajj pilgrims was lower than that of the general population in Mashhad, Iran, except for females 35–44 or more than 75 years old. The number of events occurring during the Hajj suggests that Islamic countries should consider designing preventive and screening programs for pilgrims.

     

Association of the <Emphasis Type="Italic">rs1870634</Emphasis> Variant in Long Intergenic Non-protein Coding RNA 841 with Coronary Artery Disease: A GWAS-Replication Study in an Iranian Population

Recent genome-wide association studies (GWAS) identified a list of single-nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD). Replication of GWAS findings in different population corroborated the observed association in the parent GWAS. In this study, we aimed to replicate the association of rs1870634, a GWAS identified SNP, to CAD in an Iranian population. The study population consisted of 267 subjects undergoing coronary angiography coronary angiography including 155 CAD patients and 112 non-CAD age- and gender-matched controls. The genotype determination of rs1870634 SNP performed using high-resolution melting analysis (HRM) technique. Our results revealed that the GG genotype frequency was significantly higher in CAD patients compared with controls (P?=?0.03). The results of binary logistic regression suggested that this genotype was significantly associated with CAD risk adjustment for age, BMI, sex, TC, and LDL-C lipid levels (OR of 2.78, 95% CI (1.10–7.01), P?=?0.03). Moreover, our results showed that the GG+TG genotypes were 2.52 times more likely to develop CAD (95% CI 1.05–6.03) than TT genotype carriers after adjusting for age, sex, and lipid profiles (P?=?0.037). These data showed that the GG genotype could be associated with increased risk of CAD in a sample of Iranian population.     

Prognostic significance of hemoglobin A1c level in patients hospitalized with coronary artery disease. A systematic review and meta-analysis

Background

To estimate the incidence of complications, life expectancy and diabetes related mortality in the Mexican diabetic population over the next two decades using data from a nation-wide, population based survey and the United Kingdom Prospective Diabetes Study (UKPDS) outcome model

Methods

The cohort included all patients with type 2 diabetes evaluated during the National Health and Nutrition Survey (ENSANut) 2006. ENSANut is a probabilistic multistage stratified survey whose aim was to measure the prevalence of chronic diseases. A total of 47,152 households were visited. Results are shown stratified by gender, time since diagnosis (> or ≤ to 10 years) and age at the time of diagnosis (> or ≤ 40 years).

Results

The prevalence of diabetes in our cohort was 14.4%. The predicted 20 year-incidence for chronic complications per 1000 individuals are: ischemic heart disease 112, myocardial infarction 260, heart failure 113, stroke 101, and amputation 62. Furthermore, 539 per 1000 patients will have a diabetes-related premature death. The average life expectancy for the diabetic population is 10.9 years (95%CI 10.7-11.2); this decreases to 8.3 years after adjusting for quality of life (CI95% 8.1-8.5). Male sex and cases diagnosed after age 40 have the highest risk for developing at least one major complication during the next 20 years.

Conclusions

Based on the current clinical profile of Mexican patients with diabetes, the burden of disease related complications will be tremendous over the next two decades.     

ICDs at higher age and clinical risk factors

Background

The implantable cardioverter defibrillator (ICD) is effective in preventing sudden cardiac death. However, in elderly patients (aged 75 years or older) the role of ICDs is still not well-defined and controversial.

Methods

We retrospectively analysed all clinical and survival data of all ICD patients who were ≥75 years at the date of implantation in the Erasmus MC, Rotterdam, the Netherlands and the University Hospital, Basel, Switzerland. Kaplan-Meier survival analysis was performed, and mortality predictors were identified. Mortality of the cohort was compared with a random sample of patients aged 60–70 years originating from the same database and to an age- and sex-matched cohort of Dutch persons.

Results

The study cohort consisted of 179 patients aged 75 years or older who were implanted between February 1999 and July 2008. The median follow-up time was 2.0 (IQR 2.8) years. Survival rates after 1, 2 and 3 years were 87, 82, 75 %, respectively. Survival was similar for primary and secondary prevention. Mortality in this study population could be predicted by combining four clinical risk factors: QRS duration >120 ms, NYHA class > II, renal failure and atrial fibrillation (AF). Survival was worse compared with the group of ICD patients aged 60–70 years and to the age- and sex-matched group of elderly persons. However, survival was not significantly worse when comparing elderly ICD patients without additional risk factors to the general population.

Conclusions

Elderly patients still have an acceptable survival probability independent of prevention indication, certainly if there are no additional clinical risk factors. The presence or absence of additional clinical risk factors should be taken into account when making the decision for implantation, since they strongly correlate with survival.     

The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance

Background

Type 2 diabetes mellitus (T2DM) patients are at increased risk of developing cardiovascular events. Unfortunately traditional risk assessment scores, including the Framingham Risk Score (FRS), have only modest accuracy in cardiovascular risk prediction in these patients.

Methods

We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10?years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61?±?16?months.

Results

A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0?±?4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59?±?0.07 (P?=?0.21). Among different vascular assessments, CACS?>?40 had the best prognostic value (AUC 0.81?±?0.06, P?<?0.01) and offered significantly better accuracy in prediction compared with FRS (P?=?0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS?>?40 as an independent predictor of atherosclerotic events in T2DM patients (Hazards Ratio 27.11, 95% Confidence Interval 3.36-218.81, P?=?0.002).

Conclusions

In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS?>?40 was an independent predictor for atherosclerotic events.     

Blood pressure and lipid management fall far short in persons with type 2 diabetes: results from the DIAB-CORE Consortium including six German population-based studies

Background

Although most deaths among patients with type 2 diabetes (T2D) are attributable to cardiovascular disease, modifiable cardiovascular risk factors appear to be inadequately treated in medical practice. The aim of this study was to describe hypertension, dyslipidemia and medical treatment of these conditions in a large population-based sample.

Methods

The present analysis was based on the DIAB-CORE project, in which data from five regional population-based studies and one nationwide German study were pooled. All studies were conducted between 1997 and 2006. We assessed the frequencies of risk factors and co-morbidities, especially hypertension and dyslipidemia, in participants with and without T2D. The odds of no or insufficient treatment and the odds of pharmacotherapy were computed using multivariable logistic regression models. Types of medication regimens were described.

Results

The pooled data set comprised individual data of 15, 071 participants aged 45?C74?years, including 1287 (8.5%) participants with T2D. Subjects with T2D were significantly more likely to have untreated or insufficiently treated hypertension, i.e. blood pressure of?>?= 140/90?mmHg (OR?=?1.43, 95% CI 1.26-1.61) and dyslipidemia i.e. a total cholesterol/HDL-cholesterol ratio?>?= 5 (OR?=?1.80, 95% CI 1.59-2.04) than participants without T2D. Untreated or insufficiently treated blood pressure was observed in 48.9% of participants without T2D and in 63.6% of participants with T2D. In this latter group, 28.0% did not receive anti-hypertensive medication and 72.0% were insufficiently treated. In non-T2D participants, 28.8% had untreated or insufficiently treated dyslipidemia. Of all participants with T2D 42.5% had currently elevated lipids, 80.3% of these were untreated and 19.7% were insufficiently treated.

Conclusions

Blood pressure and lipid management fall short especially in persons with T2D across Germany. The importance of sufficient risk factor control besides blood glucose monitoring in diabetes care needs to be emphasized in order to prevent cardiovascular sequelae and premature death.     

Significance of differential expression of thymidylate synthase in normal and primary tumor tissues from patients with colorectal cancer

Objective

To evaluate the efficacy of enhanced, intensive, immuno-suppressive therapy with umbilical cord blood support for severe aplastic anemia (SAA).

Methods

A total of 25 patients with SAA received enhanced, intensive, immuno-suppressive therapy and a cord blood transfusion. Therapy protocol: Anti-thymocyte globulin (ATG) 2.5 mg/(kg?d) × 5d; Cyclophosphamide 50 mg/(kg?d) × 2d; cyclosporin A (CsA) maintenance therapy.

Result

25 patients were enrolled. 18 underwent a complete recovery, 4 made significant improvements, 1 did not respond, and 2 died. Therefore, the efficacy rate was 88%. The median follow-up time was 35 months (range 13-47 months), and the 3-year overall survival rate was 92%. Patients rapidly achieved reconstitution of hematopoiesis. The median time to neutrophil ANC > 0.5 × 10⁹/L was 18 days (range 8-36), platelets >20 × 10⁹/L was 34 days (range 12-123), and Hb > 100 g/L 95 dyas (range 35-173).

Conclusion

Enhanced, intensive, immuno-suppressive therapy with umbilical cord blood support may be an effective option for SAA therapy.     

Effect of collaterals on deaths and re-infarctions in patients with coronary artery disease: a meta-analysis

Background

It is generally believed that there is a beneficial effect of collaterals on death and re-infarction statistics in patients with coronary artery disease (CAD) but studies to date are small and inconsistent.

Objective

To meta-analyse the studies published in this field in order to obtain more powerful information.

Methods

We searched Medline and major journals (2000 to 2011) for studies evaluating the effect of coronary collaterals on mortality. Publication bias, lack of heterogeneity, and lack of robustness were assessed using the standard procedures for such purposes.

Results

A total of 10 studies describing mortality, enrolling 6791 participants, were included in this analysis. In patients with collateralisation a significant relation with reduced mortality was seen compared with those without collateralisation, at an odds ratio of 0.47, p?<?0.0001, and a reduction in deaths and re-infarctions at 0.54, p?<?0.0001. Some publication bias, some heterogeneity and some lack of robustness were demonstrated. A meta-regression with the odds ratios of the presence of traditional atherosclerotic risk factors as predictors and the odds ratios of mortality and the composite deaths and re-infarctions as outcome showed no relationships.

Conclusions

In CAD patients from the post-percutaneous coronary intervention era the presence of collaterals reduced mortality by 0.47 (p?<?0.0001) and deaths and re-infarctions by 0.54 (p?<?0.0001). Furthermore, in the present meta-data, the atherosclerotic risk factors were no more present in patients with collaterals than they were in those without.     

Hypercholesterolemia and a candidate gene within the 12q24 locus

Background

The 12q24 locus entails at least one gene responsible for hypercholesterolemia. Within the 12q24 locus lies the gene of proteasome modulator 9 (PSMD9). PSMD9 is in linkage with type 2 diabetes (T2D), T2D-nephropathy and macrovascular pathology in Italian families and PSMD9 rare mutations contribute to T2D.

Aims

In the present study, we aimed at determining whether the PSMD9 T2D risk single nucleotide polymorphisms (SNPs) IVS3 + nt460 A > G, IVS3 + nt437 T > C and E197G A > G are linked to hypercholesterolemia in 200 T2D Italian families.

Methods

We characterized 200 Italian families for presence and/or absence of hypercholesterolemia characterized by LDL levels ≥ 100 mg/dl in drug-naïve patients and/or presence of a diagnosis of hypercholesterolemia in a patient treated with statin medication. The phenotypes were described as unknown in all cases in which the diagnosis was either unclear or the data were missing. We tested in the 200 Italians families for evidence of linkage of the PSMD9 SNPs with hypercholesterolemia. The non-parametric linkage analysis was performed for the qualitative phenotype by using the Merlin software; the Lod score and correspondent P-value were calculated. For the significant linkage score, 1000 replicates were performed to calculate the empirical P-value.

Results

The PSMD9 gene SNPs studied show linkage to hypercholesterolemia. The results are not due to random chance.

Conclusions

PSMD9 should be tested in all populations reporting linkage to hypercholesterolemia within the chromosome 12q24 locus. The impact of this gene on hypercholesterolemia and contribution to cardio- and cerebrovascular events may be high.     

Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk

Background

Macrovascular diseases (MVD) in type 2 diabetes mellitus (T2DM) are often considered all together, without discriminating the areas involved. The aim of our study was to analyse MVD prevalence in a large population of T2DM patients by dividing the cases into subgroups according to MVD sites (NMVD, no MVD; NSCS, non-significant carotid stenosis; CBVD, cerebrovascular disease; CAD, coronary artery disease; PAD, peripheral artery disease; PVD, polyvascular disease) and studying the anthropometric, clinical and laboratory parameters in each group.

Methods

A diabetic outpatient cohort (n = 1199) was retrospectively studied. Demographic, clinical and laboratory parameters were included in analyses. A thorough cardiovascular history as documented by previous medical records (including medical and hospital records) and vascular laboratory studies (including standardised electrocardiogram, echocardiogram, provocative tests for cardiac ischaemia, ankle/brachial index, duplex ultrasonography of the carotid and lower limbs and, in selected cases, computed tomography angiography, carotid and peripheral arteriography and evaluation of transcutaneous oxygen pressure), was collected for all of the patients. Standardised procedures were used to assess microvascular complications as well as metabolic syndrome (Mets).

Results

The unadjusted MVD prevalence was 46.4% among the participants. The majority of patients with MVD were in the PVD group. In the multivariate analysis, age, male sex and diabetes duration were independent risk factors for PAD and PVD (P < 0.01). A low HDL-C value was an independent risk factor in the CAD and PVD groups (P = 0.03). Very high frequencies of MetS were observed in the PAD and PVD groups (94.9 and 95.7% respectively). The most MetS diagnostic criteria were recorded among members of the CAD group (all or all-1 criteria were present in 73% of patients). The average age in the CAD group (64.5 y) was comparable to that of the NMVD group. Microvascular complications were more frequent in the PAD and PVD patients.

Conclusion

Phenotypic heterogeneity is associated with different macrovascular complications in T2DM patients. These findings might have clinical implications for developing diagnostic and therapeutic strategies targeting type 2 diabetes.     

Different value of coronary calcium score to predict obstructive coronary artery disease in patients with and without moderate chronic kidney disease

Purpose

The coronary calcium score (CCS) predicts significant coronary artery disease (CAD) in the general population. While moderate chronic kidney disease (CKD) is associated with high CCS, the use of CCS to predict significant CAD in these patients is unknown.

Methods

A total of 704 patients underwent computed tomography coronary angiography for the assessment of CCS and CAD. Sixty-nine (10 %) patients had moderate CKD, defined by an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73m², and the remaining patients were considered to be without significant CKD (eGFR?≥?60 mL/min/1.73m²).

Results

Patients with moderate CKD were older, had a higher CCS, and a higher prevalence of obstructive CAD than patients without significant CKD. Receiver-operator curve analysis showed that CCS predicted the presence of obstructive CAD in both patients with moderate CKD and those without significant CKD. In patients with moderate CKD, the optimal cut-off value of CCS to diagnose obstructive CAD was 140 (sensitivity 73 % and specificity of 70 %), and is 2.8 fold higher than in patients without significant CKD (cut-off value?=?50; sensitivity 75 % and specificity 75 %).

Conclusion

The present results demonstrate that CCS can predict obstructive CAD in patients with moderate CKD, although the optimal cut-off value is higher than in patients without significant CKD.     

Association of heat shock protein70-2 (HSP70-2) gene polymorphism with coronary artery disease in an Iranian population

Background

Coronary artery disease (CAD) is an inflammatory process and a major cause of mortality and morbidity. The (heat shock protein70-2) HSP70-2 gene is reported to be associated with coronary artery disease possibly by affecting the regulation of pro-inflammatory cytokines such as TNF-α. The association between CAD and the HSP70-2 gene + 1267A>G polymorphism has been studied in some populations but there are no data about this association in the Iranian population.

Aim

We have investigated the association between the HSP70-2 gene + 1267A>G polymorphism and angiographically defined CAD within an Iranian population.

Methods

We determined the presence of the HSP70-2 gene + 1267A>G polymorphism in 628 patients with CAD and 307 healthy individuals using PCR-RFLP. Of the patients, 433 (68%) had > 50% stenosis (CAD +) and the remaining 195 patients had < 50% stenosis (CAD −), based on coronary angiography. Angiogram positive patients were subdivided into three groups: those with single (n = 113), double (n = 134), and triple vessels (n = 186) disease.

Results

A significant higher frequency of AG + GG genotypes (G allele carriers) was observed in angiogram positive and angiogram negative groups compared to controls in a dominant analysis model of the HSP70-2 gene + 1267A>G position (51.2 vs. 43.2, P = 0.002, OR = 1.37) (51.0 vs. 43.2, P = 0.01, OR = 1.37). The allele frequency of the HSP70-2 G was also significantly higher in angiogram positive and angiogram negative groups compared to the control group (51.2 vs. 43.2, P = 0.002, OR = 1.37) (51.0 vs. 43.2, P = 0.01, OR = 1.37).

Conclusion

These results suggest that HSP70-2 + 1267 polymorphism may influence the risk of CAD in Iranian population, however further studies are needed to clarify the role of other HSP70-2 gene polymorphisms in the pathogenesis of the CAD.     

Strong interaction between T allele of endothelial nitric oxide synthase with B1 allele of cholesteryl ester transfer protein TaqIB highly elevates the risk of coronary artery disease and type 2 diabetes mellitus

Background

The present study was conducted to investigate the possible outcome of interaction between endothelial nitric oxide (NOS3) G894T and cholesteryl ester transfer TaqIB variants on the risk of coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). The sample included a total of 207 CAD patients (102 CAD patients with T2DM and 105 CAD patients without T2DM). There were also 101 patients with T2DM and 92 age- and sex-matched healthy individuals as controls. All study participants were from Western Iran. The sample was genotyped by polymerase chain reaction-restriction fragment length polymorphism.

Results

The presence of NOS3 T allele was not associated with the risk of CAD or T2DM, and the CETP B1 allele was only significantly associated with the increased risk of CAD in total CAD patients (odds ratio (OR)?=?5.1, p?=?0.019). However, the concomitant presence of both CETP B1 and NOS3 T alleles significantly increased the risk of CAD in total CAD patients (OR?=?18.1, p?<?0.001), in CAD patients without T2DM (OR?=?27.1, p?=?0.03), and in CAD patients with T2DM (OR?=?13.5, p?=?0.002). Also, the presence of both alleles increased the risk of T2DM (OR?=?12, p?=?0.004).

Conclusions

Our findings, for the first time, indicate that NOS3 T allele strongly interacts with CETP B1 allele to augment the risk of CAD and T2DM in the population of Western Iran.     

Multi-cancer computational analysis reveals invasion-associated variant of desmoplastic reaction involving INHBA, THBS2 and COL11A1

Background

The inability of aspirin (ASA) to adequately suppress platelet aggregation is associated with future risk of coronary artery disease (CAD). Heritability studies of agonist-induced platelet function phenotypes suggest that genetic variation may be responsible for ASA responsiveness. In this study, we leverage independent information from genome-wide linkage and association data to determine loci controlling platelet phenotypes before and after treatment with ASA.

Methods

Clinical data on 37 agonist-induced platelet function phenotypes were evaluated before and after a 2-week trial of ASA (81 mg/day) in 1231 European American and 846 African American healthy subjects with a family history of premature CAD. Principal component analysis was performed to minimize the number of independent factors underlying the covariance of these various phenotypes. Multi-point sib-pair based linkage analysis was performed using a microsatellite marker set, and single-SNP association tests were performed using markers from the Illumina 1 M genotyping chip from deCODE Genetics, Inc. All analyses were performed separately within each ethnic group.

Results

Several genomic regions appear to be linked to ASA response factors: a 10 cM region in African Americans on chromosome 5q11.2 had several STRs with suggestive (p-value < 7 × 10^-4) and significant (p-value < 2 × 10^-5) linkage to post aspirin platelet response to ADP, and ten additional factors had suggestive evidence for linkage (p-value < 7 × 10^-4) to thirteen genomic regions. All but one of these factors were aspirin response variables. While the strength of genome-wide SNP association signals for factors showing evidence for linkage is limited, especially at the strict thresholds of genome-wide criteria (N = 9 SNPs for 11 factors), more signals were considered significant when the association signal was weighted by evidence for linkage (N = 30 SNPs).

Conclusions

Our study supports the hypothesis that platelet phenotypes in response to ASA likely have genetic control and the combined approach of linkage and association offers an alternative approach to prioritizing regions of interest for subsequent follow-up.