Interaction of apolipoprotein E genotype with smoking and physical inactivity on coronary heart disease risk in men and women

ObjectiveApolipoprotein E genotype (APOE) polymorphism affects lipid levels and coronary heart disease (CHD) risk. However, these associations may be modified by lifestyle factors. Therefore, we studied whether smoking, physical inactivity or overweight interact with APOE on cholesterol levels and CHD risk.MethodsCombining two Swedish case-control studies yielded 1735 CHD cases and 4654 population controls (3747 men, 2642 women). Self-reported questionnaire lifestyle data included smoking (ever [current or former regular] or never) and physical inactivity (mainly sitting leisure time). We obtained LDL cholesterol levels and APOE genotypes. CHD risk was modelled using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for relevant covariates.ResultsSmoking interacted with APOE on CHD risk; adjusted ORs for ever versus never smoking were 1.45 (95% CI 1.00–2.10) in ?2 carriers, 2.25 (95% CI 1.90–2.68) in ?3 homozygotes and 2.37 (95% CI 1.85–3.04) in ?4 carriers. Female ?4 carriers had OR 3.62 (95% CI 2.32–5.63). The adjusted ORs for physical inactivity were 1.09 (95% CI 0.73–1.61), 1.34 (95% CI 1.12–1.61), and 1.79 (95% CI 1.38–2.30) in ?2, ?3?3 and ?4 groups, respectively. No interaction was seen between overweight and APOE for CHD risk, or between any lifestyle factor and APOE for LDL cholesterol levels.ConclusionThe APOE ?2 allele counteracted CHD risk from smoking in both genders, while the ?4 allele was seen to potentiate this risk mainly in women. Similar ?2 protection and ?4 potentiation was suggested for CHD risk from physical inactivity.     

XPC Lys939Gln polymorphism,smoking and risk of sporadic colorectal cancer among Malaysians

AIM: To investigate the risk association of xeroderma pigmentosum group C (XPC ) Lys939Gln polymorphism alone and in combination with cigarette smoking on colorectal cancer (CRC) predisposition. METHODS: Peripheral blood samples of 510 study subjects (255 CRC patients, 255 controls)were collected. DNA was extracted and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. The association between polymorphic genotype and CRC predisposition was determined using the OR and 95%CI. RESULTS: The frequency of the homozygous variant (Gln/Gln) genotype was significantly higher in cases compared with controls (16.0% vs 10.2%, P = 0.049). The Gln/Gln genotype of XPC showed a significantly higher association with the risk of CRC (OR = 1.884; 95%CI: 1.082-3.277; P = 0.025). In the case of allele frequencies, variant allele C was associated with a significantly increased risk of CRC (OR = 1.375; 95%CI: 1.050-1.802; P = 0.020). Moreover, the risk was markedly higher for those who were carriers of the Gln/Gln variant genotype and were also cigarette smokers (OR = 3.409; 95%CI: 1.061-10.949; P = 0.032). CONCLUSION: The XPC Gln/Gln genotype alone and in combination with smoking increases the risk of CRC among Malaysians.     

Association of AdipoQ single-nucleotide polymorphisms and smoking interaction with the risk of coronary heart disease in Chinese Han population

Aims: To investigate the impact of AdipoQ polymorphisms, and their additional interactions with smoking and drinking on coronary heart disease (CHD) risk based on Chinese population. Methods: Hardy?Weinberg equilibrium (HWE) was performed using SNPStats (available online at http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) model was used to screen the best gene?gene and gene?environment interaction combinations. Logistic regression was performed to investigate association between four single-nucleotide polymorphisms (SNPs) and CHD and the interaction effect between rs1501299 and smoking. Results: Logistic analysis showed that CHD risks were higher in carriers with homozygous mutant of rs1501299 and rs2241766 than those with wild-type homozygotes, odds ratio (ORs) (95%CI) were 1.49 (1.19–1.95) and 1.71 (1.33–2.24), respectively, but CHD risks were lower in carriers with homozygous mutant of rs7649121 than those with wild-type homozygotes, OR (95%CI) was 0.72 (0.51–0.96). GMDR model indicated that there was a significant two-locus model (p = 0.0107) involving rs1501299 and current smoking, indicating a potential gene–environment interaction between rs1501299 and current smoking. Overall, the cross-validation consistency of this model was 9/10, and the testing accuracy was 60.11% (p = 0.0010). T-allele carriage had 42% prevalence, and one-quarter of them were current smokers. Smokers with rs1501299-GT or TT genotype have the highest CHD risk, compared to never-smokers with rs1501299-GG genotype, OR (95%CI) was 3.56 (1.91–5.42), after adjustment for gender, age, alcohol status, and body mass index. But we did not find any significant gene–gene and gene–drinking interaction combinations in GMDR models. Conclusions: Polymorphisms in rs1501299 and rs2241766, and their additional interactions between rs1501299 and smoking were associated with increased CHD risks: polymorphism in rs7649121 was associated with decreased CHD risks.     

Factors associated with 2-year persistence in fully non reimbursed lipid-lowering treatments

Objective

to evaluate the main factors associated with long-term persistence in fully paid lipid-lowering treatment.

Methods

We selected 628 moderately hypercholesterolemic subjects (M: 307; F: 311, mean age 59 ± 9 years old), to whom we firstly prescribed a statin (N. 397) or different kinds of lipid-lowering nutraceuticals (N. 231). Then, depending on their will, patients took brand statin (N. 194) or generic statins (N. 203).

Results

The main determinants of long-term persistence in therapy are female sex (OR 1.21, 95%CI 1.08–1.42), family history of early cardiovascular disease (OR 1.31, 95%CI 1.13–1.49), baseline LDL-C (OR 1.19, 95%CI 1.02–1.33) and treatment with nutraceuticals versus statins (OR 1.29, 95%CI 1.14–1.38). Persistence appears not to be influenced by patient's age, smoking habit, adverse events during treatment, and estimated cardiovascular risk.

Conclusion

Among self-paying patients with mild hyperlipidemia, medication persistence is highest among those taking nutraceuticals, followed by brand statins, followed by generic statins.     

Effect of smoking and other traditional risk factors on the onset of coronary artery calcification: Results of the Heinz Nixdorf recall study

Background

Coronary artery calcium (CAC) indicates coronary atherosclerosis and can be present in very early stages of the disease. The conversion from no CAC to any CAC reflects an important step of the disease process as cardiovascular risk is increased in persons even with mildly elevated CAC. We sought to identify risk factors that determined incident CAC>0 in men and women from an unselected general population with a special focus on the role of smoking.

Methods

All 4814 persons that were initially studied in the Heinz Nixdorf Recall Study were invited to participate in the follow-up examination after 5.1 ± 0.3 years. All traditional Framingham risk factors were quantified using standard techniques. Smokers were categorized in never, former and present smokers. The CAC scores were measured from EBCT using the Agatston method.

Results

Overall, out of 342 men and 919 women with zero CAC at baseline, 107 (31.3%) men and 210 (22.9%) women had CAC>0 at second examination. In multivariable analysis, age (OR estimate per 5 years: 1.34 (95%CI: 1.21–1.47)), LDL cholesterol (per 10 mg/dL: 1.05 (95%CI: 1.01–1.10)), systolic blood pressure (per 10 mmHg: 1.19 (95%CI: 1.11–1.28)) and current smoking (1.49 (95%CI: 1.04–2.15)) were independent predictors of CAC onset. The probability of CAC onset steadily increased with age from 23.3% (men) and 15.3% (women) at age 45–49 years to 66.7% (men) and 42.9% (women) at age 70–74 years. The difference in age-dependent conversion rates was quantified by years between reaching a given level of CAC onset probability. We found a consistent pattern with respect to smoking status: presently (formerly) smoking middle-aged men convert to positive CAC 10 (5) years earlier than never smokers, for women (middle-aged to elderly) this time span is 8 (5) years.

Conclusion

Several traditional CVD risk factors are associated with CAC onset during 5 years follow-up. CAC onset is accelerated by approximately 10 (5) years for present (former) compared to never smokers.     

Accumulation of oxidative stress-related gene polymorphisms and the risk of coronary heart disease events in patients with type 2 diabetes – An 8-year prospective study

Objective

Oxidative stress, which is provoked in patients with diabetes, plays critical roles in the pathogenesis of coronary heart disease (CHD). We simultaneously determined 5 relatively common genetic variants related to oxidative stress and evaluated the combined effect on CHD.

Methods

We enrolled 1977 Japanese type 2 diabetic subjects without history of CVD (males 66.1%, 59.5 ± 10.0 years old), determined their genotypes regarding glutamate-cysteine ligase modifier subunit (GCLM) C-588T, manganese superoxide dismutase (SOD2) Val16Ala, endothelial nitric oxide synthase (NOS3) G894T, NAD(P)H oxidase p22phox (CYBA) C242T, and myeloperoxidase (MPO) G-463A polymorphisms, and prospectively evaluated the association between these polymorphisms and CHD events.

Results

The median follow-up period was 7.5 years and there were 85 new CHD events. The single association analysis revealed that there were no statistically significant associations between each polymorphism and the prevalence of CHD. Interestingly, the risk of CHD event was higher with the increase of the total number of 10 concomitant unfavorable “pro-oxidant alleles” in each subject (p for trend = 0.018, log-rank test). Especially, the carriers of ≥8 pro-oxidant alleles had a significantly increased risk as compared to the carriers of <8 pro-oxidant alleles, whether the other clinical variables were adjusted (HR 2.92 with 95%CI 1.50–5.67, p = 0.002) or not (HR 2.89 with 95%CI 1.49–5.59, p = 0.002)..

Conclusions

Accumulation of gene polymorphisms related to oxidative stress is likely associated with the development of CHD in patients with type 2 diabetes, suggesting that the combined information about these variants is useful to assess the risk of CHD.     

Association between leukocyte mitochondrial DNA content and risk of coronary heart disease: A case-control study

Objective

Compelling epidemiological evidence indicates that alterations of mitochondrial DNA (mtDNA), including mutations and abnormal content of mtDNA, are associated with the initiation and development of cardiovascular disease. This study was undertaken to investigate whether mtDNA content in peripheral blood leukocytes (PBLs) could be used as a risk predictor for coronary heart disease (CHD).

Methods

The mtDNA content of PBLs from 378 CHD patients and 378 matched healthy controls was measured using quantitative real-time PCR-based method in a case-control study. An unconditional multivariate logistic regression model was applied to estimate the association between leukocyte mtDNA content and CHD risk.

Results

CHD patients exhibited notably lower mtDNA content than matched healthy controls (median, 0.65 vs. 0.86; P < 0.001). Compared with individuals who had high mtDNA content, individuals who had low mtDNA content had a significantly increased risk of CHD (adjusted OR, 2.38; 95% confidence interval, 1.33–4.69). A significant dose–response relation was observed between increased CHD risk and lower mtDNA content (P_trend < 0.001). Furthermore, there was a significantly positive mtDNA content correlation between PBLs and atherosclerotic plaque tissue (ρ = 0.627, P = 0.039). In addition, a significant joint effect on the risk of CHD was noted between mtDNA content and cigarette smoking or plasma LDL-C concentration.

Conclusions

This present study provide the first epidemiologic evidence linking low mtDNA content in PBLs to an increased CHD risk, which warrants further investigation in other populations.     

APOE polymorphism and carotid atherosclerosis in Korean population: The Dong-gu Study and the Namwon Study

Objective

We evaluated the association between APOE polymorphism and carotid atherosclerosis in two large independent cohorts from South Korea.

Methods

The datasets were from the Dong-gu Study (N = 9056) and the Namwon Study (N = 10,158). Carotid ultrasonography was performed to measure carotid intima-media thickness (IMT) and the presence of carotid plaques. The APOE polymorphism was determined by PCR-RFLP. We performed combined and separate analyses for the two datasets.

Results

In the combined analysis, individuals with E2E2 or E2E3 genotype had a lower common carotid IMT compared with individuals with E3E3 genotype (0.684 mm vs. 0.736 mm, p = 0.007; 0.718 mm vs. 0.736 mm, p < 0.001, respectively). This association was very slightly attenuated but remained statistically significant after adjustment for blood lipids (0.690 mm vs. 0.736 mm, p = 0.033; 0.725 mm vs. 0.736 mm, p = 0.005, respectively). Compared with individuals with E3E3 genotype, individuals with E2E3 genotype had lower risk for carotid plaque (odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.75–0.93), while individuals with E3E4 genotype had a higher risk for carotid plaque (OR = 1.09, 95% CI = 1.00–1.20). After adjustment for blood lipids, ORs of E2E3 genotype for carotid plaque was slightly attenuated but remained significant (OR = 0.87 95% CI = 0.78–0.97), while OR of E3E4 genotype were slightly attenuated and not significant (OR = 1.08, 95% CI, 0.99–1.18).

Conclusions

We found that APOE polymorphism is associated with carotid atherosclerosis and this association was partly mediated through blood lipid. Our results suggest that APOE polymorphism may influence atherosclerosis through non-lipid pathways.     

Human plasma complement C3 is independently associated with coronary heart disease, but only in heavy smokers (the CODAM study)

Background

Complement C3 is an emerging risk factor for coronary heart disease (CHD) and is particularly increased in the metabolic syndrome. A direct effect of smoking on structure and function of complement C3 has been suggested.

Hypothesis

Smoking behavior may affect the cardiovascular risk that is associated with plasma complement C3.

Methods

The association between plasma C3 and CHD was studied in the CODAM (Cohort on Diabetes and Atherosclerosis Maastricht) study population (n = 562, 61% male) with examination of effect modification by smoking.

Results

The overall prevalence of CHD was 23.3%. Higher plasma C3 levels were associated with a higher CHD prevalence, and there was a significant interaction with heavy smoking (p = 0.01). In never & light smokers, the univariate OR for CHD per 1 s.d. (0.33 g/L) increase in C3 was 1.09 [95% confidence interval (CI) 0.85-1.41] (p = 0.505) whereas in heavy smokers it was 2.05 [1.43-2.93] (p < 0.001). The association in the group of heavy smokers remained significant (OR 2.38 [1.54-3.68], p < 0.001) after adjustment for traditional risk factors for cardiovascular disease and also after further adjustment for other cardiometabolic risk factors, i.e. the metabolic syndrome, CRP and insulin resistance (HOMA2IR) (OR C3 between 2.16 and 2.29, all p ≤ 0.001).

Conclusion

Human plasma complement C3 is associated with prevalent CHD, but only in heavy smokers, and this association is independent of important metabolic cardiovascular risk factors.     

Association of peroxisome proliferator-activated receptor delta and additional gene–smoking interaction on cardiovascular disease

Aims: To investigate the impact of peroxisome proliferator–activator receptor delta (PPARD) gene polymorphism and additional gene–smoking interaction on cardiovascular disease (CVD) risk based on this Chinese population. Methods: A total of 1048 subjects (617 males, 431 females) with a mean age of 52.9 ± 14.1 years old were selected, including 520 CVD patients and 528 normal control subjects. The logistic regression model was used to examine the association between three SNPs and CVD risk, odds ratio (OR), and 95% confident interval (95%CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to investigate the gene–smoking interaction. Results: Genotypes of variants in rs2016520 and rs9794 were associated with decreased CVD risk, and CVD risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with the TT genotype (TC+CC versus TT), adjusted OR (95%CI) = 0.71 (0.56–0.86). In addition, we also found that CVD risk was also significantly lower in carriers of the G allele of the rs9794 polymorphism than those with the CC genotype (CG+ GG versus CC), adjusted OR (95%CI) = 0.69 (0.53–0.86). GMDR analysis suggested a potential gene–environment interaction between rs2016520 and smoking. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 62.17%, and never smokers with TC or CC of the rs2016520 genotype have the lowest CVD risk, compared to smokers with TT of rs2016520, OR (95%CI) was 0.42 (0.23–0.66). Conclusions: The minor allele of rs2016520 and rs9794 in PPAR-δ and interaction between rs2016520 and non-smoking were associated with decreased risk of CVD.     

No APOEepsilon4 effect on coronary heart disease risk in a cohort with low smoking prevalence: the Whitehall II study

Carriers of the APOEepsilon4 allele have consistently shown higher, and epsilon2 carriers have lower, plasma cholesterol and coronary heart disease (CHD) risk compared with epsilon3 homozygotes. An epsilon4:smoking interaction was observed in NPHSII, consistent with context dependency of the epsilon4 effect on CHD risk. In this study, APOE genotype was determined in 3787 male British civil servants followed for fatal and non-fatal myocardial infarction for median of 5.8 years, with 159 validated CHD events. APOE genotype was associated with expected effects on lipid traits (all P <0.0001). We tested the hypothesis that APOEepsilon4 was not a risk factor for CHD among non-smokers. In non-smokers, the odds ratio (OR) for epsilon2 and epsilon4 carriers were 0.51 (0.27, 0.97) and 0.70 (0.46, 1.08), respectively, compared with epsilon3 homozygotes. Thus epsilon2 carriers showed expected risk-protection, but despite 80% power to detect an OR in epsilon4 subjects of 1.71 (i.e. of magnitude increase reported in prospective studies), the epsilon4 non-smokers showed no increased risk compared with epsilon3 homozygotes. Smoking prevalence in this study was low (12.8%), but smokers had higher CHD risk which was of similar magnitude in risk in all genotypes [(OR 1.57 (1.03, 2.40)]. These data, therefore, provide strong corroborative evidence that there is no elevated risk of CHD in epsilon4 non-smokers, but failed to confirm the epsilon4:smoking interaction on risk. This supports the context dependency of the epsilon4 risk effect, but the low smoking incidence in the Whitehall men reduced our ability to examine a smoking:genotype interaction.     

APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans

AIM: To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.METHODS: Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ² tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility.RESULTS: The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m² (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter polymorphism -141 T/G genotype was associated with a reduced risk of colorectal cancer among subjects with a BMI < 25 kg/m² (OR = 0.214, 95%CI: 0.069-0.660, P < 0.05 relative to T/T genotype). There were significant gene-behavior interactions between smoking status and XRCC1 Arg399Gln, as well as BMI and APE1 -141T/G polymorphism (all P < 0.05).CONCLUSION: APE1 Asp148Glu is associated with increased CRC risk and smoking alters the association between XRCC1 Arg399Gln and CRC risk in the Chinese Han population.     

Sugar sweetened beverages consumption and risk of coronary heart disease: A meta-analysis of prospective studies

Objective

To summarize the evidence with respect to sugar sweetened beverages (SSBs) consumption and risk of coronary heart disease (CHD) and to recommend field standards for future analysis on this topic.

Methods

We searched for articles published up to February 2013 through PubMed, EMbase, and Cochrane Library Database and reviewed reference list of the retrieved articles. Prospective studies with reported relative risks (RRs) with 95% confidence intervals (CIs) of CHD for different categories of SSBs consumption were included. Random-effects models were used to evaluate the associations by comparing the highest and lowest categories of SSBs consumption in relation to risk of CHD.

Results

Four prospective studies with 7396 CHD cases among 173,753 participants were included in the meta-analysis. The pooled RR (95% CI) for CHD in the highest category of SSBs consumption in comparison with the lowest category of SSBs was 1.17 (1.07–1.28). Stratified analyses indicated a significant association for men but not for women, with pooled RRs (95%CI) of 1.17 (1.05–1.29) and 1.19 (0.94–1.50), respectively. For studies carried out in America, the pooled RR for CHD was 1.18 (1.07–1.30). Additionally, a one-severing per day increase in SSBs consumption was associated with a 16% increased risk of CHD (RR: 1.16, 95%CI: 1.10–1.23).

Conclusion

Our meta-analysis of four studies suggests that consumption of SSBs may increase risk of CHD, especially among men and American populations. However, this finding was based on limited studies; further studies are warranted to critically evaluate the relationship.     

Influence of obesity and malnutrition on acute heart failure

Introduction and objectives

Obesity is an independent risk factor for the development of heart failure. Several recent studies have found better outcomes of heart failure for obese patients, an observation termed as the “obesity paradox.” On the other hand, the negative effect of malnutrition on the evolution of heart failure has also been clearly established.

Methods

Data from the Minimum Basic Data Set were analyzed for all patients discharged from all the departments of internal medicine in hospitals of the Spanish National Health System between the years 2006 and 2008. The information was limited to those patients with a primary or secondary diagnosis of heart failure. Patients with a diagnosis of obesity or malnutrition were identified. The mortality and readmission indexes of obese and malnourished patients were compared against the subpopulation without these diagnoses.

Results

A total of 370 983 heart failure admittances were analyzed, with 41 127 (11.1%) diagnosed with obesity and 4105 (1.1%) with malnutrition. In-hospital global mortality reached 12.9% and the risk of readmission was 16.4%. Obese patients had a lower in-hospital mortality risk (odds ratio [OR]: 0.65, 95% confidence interval [95%CI]: 0.62-0.68) and early readmission risk (OR: 0.81, 95%CI: 0.78-0.83) than nonobese patients. Malnourished patients had a much higher risk of dying while in hospital (OR: 1.83 95%CI: 1.69-1.97) or of being readmitted within 30 days after discharge (OR: 1.39, 95%CI: 1.29-1.51), even after adjusting for possible confounding factors.

Conclusions

Obesity in patients admitted for HF substantially reduces in-hospital mortality risk and the possibility of early readmission, whereas malnutrition is associated with important increases in in-hospital mortality and risk of readmission in the 30 days following discharge.Full English text available from:www.revespcardiol.org     

Traditional Cardiovascular Risk Factors and the Presence of Obstructive Coronary Artery Disease in Men and Women

Background

Extensive research has demonstrated the importance of traditional cardiovascular risk factors in predicting acute coronary events. Our main objective was to evaluate the relationship between traditional risk factors and the presence of obstructive coronary artery disease (CAD), and to explore potential differences in men vs women.

Methods

An observational study was conducted in a population-based cohort of stable patients who underwent cardiac catheterization in Ontario, Canada. We examined the relationship of diabetes, hypertension, hyperlipidemia, and smoking with the presence of obstructive CAD in men and women using multivariable logistic regression models.

Results

Of the 46,490 patients who were included in our study, 61.2% were men and 38.8% were women. We found that 97% of patients with obstructive CAD had at least 1 conventional cardiovascular risk factor. The adjusted odds ratios (ORs) for obstructive CAD in women with diabetes (OR, 1.51), hypertension (OR, 1.38), and smoking (OR, 1.39) were statistically significantly greater than in men (OR, 1.20 for diabetes; OR, 1.08 for hypertension; OR, 1.14 for smoking; P < 0.001). The sex difference was even greater for patients with multiple risk factors. For example, the association with obstructive CAD in women with 4 cardiac risk factors (OR, 4.30; 95% confidence interval, 3.49-5.28) was almost doubled compared with men (OR, 2.26; 95%confidence interval, 1.99-2.57; P < 0.001).

Conclusions

Almost all patients with stable CAD undergoing cardiac catheterization had at least 1 traditional cardiac risk factor. Importantly, the association between multiple cardiac risk factors and the presence of obstructive CAD is substantially stronger in women than men.     

Dose-dependent effect of smoking on risk of coronary heart disease,heart failure and stroke in individuals with type 1 diabetes

Aims/hypothesis

The aim of this study was to assess the potential dose-dependent effects of smoking on the risk of CHD, heart failure and stroke in individuals with type 1 diabetes.

Methods

The study included 4506 individuals with type 1 diabetes who were participating in the Finnish Diabetic Nephropathy (FinnDiane) study. Intensity of smoking was estimated by packs per day and cumulative smoking by pack-years. Cox regression analyses were used to estimate the risk of incident CHD, heart failure or stroke during follow-up.

Results

One pack per day significantly increased the risk of incident CHD in current smokers compared with never smokers (HR 1.45 [95% CI 1.15, 1.84]), after adjustment for age, sex, HbA_1c, hypertension, duration of diabetes and BMI. The risk of CHD in former smokers was similar to the risk in never smokers. The risk of incident heart failure was 1.43 (95% CI 1.03, 1.97) in current smokers per one pack per day and 1.37 (95% CI 1.05, 1.77) in former smokers, while the risk of incident stroke was 1.70 (95% CI 1.26, 2.29) and 1.49 (95% CI 1.14, 1.93), respectively. After further adjustments for lipids, however, the difference in the risk of heart failure in current and former smokers was no longer significant. Cumulative smoking data were similar to smoking intensity data.

Conclusions/interpretation

There is a dose-dependent association between smoking and cardiovascular disease in individuals with type 1 diabetes. In men in particular, the risk of incident stroke remains high even after smoking cessation and is increased in current and former smokers independently of other risk factors.

     

Endothelial nitric oxide synthase Glu 298 Asp (G894T) and Apolipoprotein E gene polymorphism as possible risk factors for coronary heart disease among Egyptians

In Egypt, The prevalence of chronic heart disease (CHD) is 8.3%. It is the principal cause of death and is responsible for 22% of total mortality. The age-adjusted mortality rate is 174 per 100,000 of population. There are many studies on traditional risk factors and CHD in Egypt but the study of novel risk factors is deficient.

Diagnosis performance of high sensitivity troponin assay in out-of-hospital cardiac arrest patients

Purpose

Early identification of the cause of out-of-hospital cardiac arrest (OHCA) remains a challenge. Our aim was to determine whether high-sensitivity cardiac troponin T (HsTnT) was useful to diagnose a recent coronary artery occlusion as the cause of OHCA.

Methods

Retrospective study including OHCA patients evaluated by systematic coronary angiogram at hospital admission. HsTnT was assessed at ICU admission. Predictive factors of a recent coronary occlusion were identified by logistic regression. Net reclassification improvement (NRI) was calculated to estimate the potential enhancement of prediction with HsTnT.

Results

During the 5 year study period, 272 patients (median age 60y, 76.5% men) were included, and a culprit coronary occlusion was found in 133 (48.9%). The optimum HsTnT cut-off to predict a recent coronary occlusion was 575 ng/l (sensitivity 65.4%, specificity 65.5%). In multivariate analysis, current smoking (OR 3.2 95%, 95%CI 1.62–6.33), time from collapse to BLS < 3 min (OR 2.11, 95%CI 1.10–4.05), initial shockable rhythm (OR 5.29, 95%CI 2.06–13.62), ST-segment elevation (OR 2.44, 95%CI 1.18–5.03), post-resuscitation shock onset (OR 2.03, 95%CI 1.01–4.07) and HsTnT ≥ 575 ng/l (OR 2.22, 95%CI 1.16–4.27) were associated with the presence of a recent coronary occlusion. Nevertheless, adding HsTnT to established risk factors of recent coronary occlusion identified above provided a non-significant NRI of − 0.43%.

Conclusions

Admission HsTnT is increased after OHCA and is an independent factor of a recent coronary occlusion. However, HsTnT does not seem to be a strong enough diagnostic tool to select candidates for emergent coronary angiogram in OHCA survivors.     

Association of Interleukin-6 Genetic Polymorphisms and Environment Factors Interactions with Coronary Artery Disease in a Chinese Han Population

Objectives: To investigate the influence of IL-6 single nucleotide polymorphisms (SNPs), additional gene-gene and gene-environment interactions on coronary artery disease (CAD) risk. Methods: A total of 751 participants (429 CAD patients and 322 controls) were recruited in this study. Logistic regression analysis was conducted to evaluate the association of IL-6 SNPs with CAD risk and generalized multifactor dimensionality reduction (GMDR) was performed to investigate the best interaction combinations for gene-gene and gene-environment interactions. Results: CAD risk is significantly higher in carriers of C allele of the rs1800795 polymorphism than those with GG genotype (CC + CG versus GG, adjusted OR (95%CI) = 2.07 (1.56–2.86), p < 0.001). GMDR analysis revealed rs1800795 was significantly interacted with tobacco smoking and alcohol drinking in two-locus model (p < 0.0010). Current smokers with CC or CG of rs1800795 genotype have the highest CAD risk, OR (95%CI) = 3.22 (2.45–3.94) and current drinkers with CC or CG of rs1800795 genotype have the highest CAD risk, OR (95%CI) = 3.17 (2.20–4.24). Conclusion: The C allele of rs1800795 within IL-6 gene promoter, rs1800795-tobacco smoking and rs1800795-alcohol drinking interaction were all associated with increased CAD risk.