Family History Of Myocardial Infarction Research Articles

Coronary risk assessment among intermediate risk patients using a clinical and biomarker based algorithm developed and validated in two population cohorts

Background:Many coronary heart disease (CHD) events occur in individuals classified as intermediate risk by commonly used assessment tools. Over half the individuals presenting with a severe cardiac event, such as myocardial infarction (MI), have at most one risk factor as included in the widely used Framingham risk assessment. Individuals classified as intermediate risk, who are actually at high risk, may not receive guideline recommended treatments. A clinically useful method for accurately predicting 5-year CHD risk among intermediate risk patients remains an unmet medical need.Objective:This study sought to develop a CHD Risk Assessment (CHDRA) model that improves 5-year risk stratification among intermediate risk individuals.Methods:Assay panels for biomarkers associated with atherosclerosis biology (inflammation, angiogenesis, apoptosis, chemotaxis, etc.) were optimized for measuring baseline serum samples from 1084 initially CHD-free Marshfield Clinic Personalized Medicine Research Project (PMRP) individuals. A multivariable Cox regression model was fit using the most powerful risk predictors within the clinical and protein variables identified by repeated cross-validation. The resulting CHDRA algorithm was validated in a Multiple-Ethnic Study of Atherosclerosis (MESA) case-cohort sample.Results:A CHDRA algorithm of age, sex, diabetes, and family history of MI, combined with serum levels of seven biomarkers (CTACK, Eotaxin, Fas Ligand, HGF, IL-16, MCP-3, and sFas) yielded a clinical net reclassification index of 42.7% (p < 0.001) for MESA patients with a recalibrated Framingham 5-year intermediate risk level. Across all patients, the model predicted acute coronary events (hazard ratio = 2.17, p < 0.001), and remained an independent predictor after Framingham risk factor adjustments.Limitations:These include the slightly different event definition with the MESA samples and inability to include PMRP fatal CHD events.Conclusions:A novel risk score of serum protein levels plus clinical risk factors, developed and validated in independent cohorts, demonstrated clinical utility for assessing the true risk of CHD events in intermediate risk patients. Improved accuracy in cardiovascular risk classification could lead to improved preventive care and fewer deaths.

Relation between objective measures of atopy and myocardial infarction in the United States

Although rodent studies indicate that atherosclerosis is a T(H)1-mediated disease and that atopic T(H)2 immunity is atheroprotective, findings in humans are conflicting. Total IgE (tIgE) is associated with atherosclerotic disease but has limited specificity for atopy. Our aim was to determine the relation between atopy, as indicated by a broad panel of serum allergen-specific IgE (sIgE), and past myocardial infarction (MI) in a sample representative of the US population. Data were analyzed from 4002 participants aged ≥ 20 years from the 2005-2006 National Health and Nutrition Examination Survey. Subjects reporting a history of MI had lower summed sIgE (5.51 vs 7.71 kU/L; P < .001) and were less likely to have ≥ 1 positive sIgE test (29.9% vs 44.6%; P = .02) or current hay fever (3.3% vs 7.6%; P = .002). After adjustment for age, sex, race/ethnicity, diabetes mellitus, hypertension, family history of MI, smoking, total/high-density lipoprotein cholesterol, body mass index, and C-reactive protein, the odds ratio (OR) for MI was 0.91 (95% CI, 0.85-0.97) per positive sIgE; 0.70 (95% CI, 0.57-0.85) per 2-fold increase in sum[sIgE]; and 0.82 (95% CI, 0.69-0.98) per 10% increase in the ratio of sum[sIgE] to tIgE. Analysis with 7 data-driven, prespecified allergen clusters found that house dust mite is the only allergen cluster for which sIgE is associated with reduced odds for MI (fully adjusted OR, 0.36; 95% CI, 0.20-0.64). Serum sIgE is inversely related to MI in the US population in a manner independent of multiple coronary risk factors.

Vitamin D deficiency in postmenopausal, healthy women predicts increased cardiovascular events: a 16-year follow-up study

To investigate the relationship between vitamin D status in healthy women and cardiovascular outcome. Between 1990 and 1993, 2016 healthy, recently postmenopausal women were enrolled in the Danish Osteoporosis Prevention Study. Serum levels of 25-hydroxyvitamin D (25(OH)D, nmol/l) were measured at baseline. Participants were followed for 16 years. The primary end point was a combination of death, heart failure, myocardial infarction (MI) and stroke. Vitamin D deficiency was defined as serum 25(OH)D<50 nmol/l. The primary end point was adjusted for other risk factors of adverse cardiovascular events (age, smoking, blood pressure, hip-waist ratio, education and family history of MI). At baseline, mean age was 50 years and BMI 25. Women with vitamin D deficiency (n=788) had more cardiovascular risk factors than vitamin D-replete women (n=1225). Compared with vitamin D-replete women, women with low 25(OH)D levels had significantly higher BMI and triglycerides, lower HDL and hip-waist ratio and less education. More were smokers among the vitamin D deficient (47 vs 38%). A primary end point was experienced by 118 (15%) with vitamin D deficiency and by 125 (10%) of the vitamin D replete. Hazard ratio (HR) was 1.49 (95% confidence interval: 1.16-1.92; P=0.002) in the vitamin D deficient. Adjusted HR was 1.32 (1.02-1.71; P=0.03). In total, 135 women died; of these, 65 (8%) were of the vitamin D deficient and 70 (6%) in the vitamin D-replete group; unadjusted HR was 1.44 (1.02-2.01; P=0.04) for vitamin D deficiency. Healthy women with vitamin D deficiency have increased risk of adverse cardiovascular outcome.

Family history of myocardial infarction is a risk factor for venous thromboembolism among whites but not among blacks.

In addition to potentially sharing common pathogenesis and clinical manifestations, venous and arterial thromboses might have overlapping risk factors. To evaluate the family history of myocardial infarction (MI) as a risk factor for venous thromboembolism (VTE) among whites and blacks, we analyze data from the Genetic Attributes and Thrombosis Epidemiology (GATE) study. Results indicate that the association between VTE and a family history of MI is statistically significant only among whites (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.03-1.8), particularly when they have diabetes mellitus (OR = 3.1; 95% CI = 1.2-8.0). Among blacks, the association between VTE and a family history of MI is not statistically significant (OR = 1.2; 95% CI = 0.89-1.5) either among those with diabetes or those without diabetes. We conclude that a family history of MI is a risk factor for VTE among certain populations stratified by race and comorbid conditions.

A Study of Thrombophilia Testing and Counseling Practices of Family Physicians Using the Script Concordance Method in Calgary, Canada

Thrombophilia testing helps to identify populations at risk of venous thromboembolism, but motivations for testing individuals are frequently unclear. Our goals were to assess the motivations for thrombophilia testing among family physicians (FPs) to determine whether testing was congruent with expert opinion, and to study counseling practices. The FPs and experts completed a survey involving hypothetical thrombophilia patients. Responses between groups were compared using the script concordance method. The FPs referred 35.9% of cases. Of the five scenarios, two resulted in disagreement regarding appropriateness of testing (P ≤ .037). The FPs were more likely to test male, obese, or pediatric patients, patients with a family history of myocardial infarction or infertility, and patients with a recent event (P ≤ .043). The FPs were more likely to counsel patients after testing (P ≤ .016). Disagreement exists between physician groups about the utility of thrombophilia testing. Self-reported lack of pretest counseling among FPs warrants further study.

Digital And Palmar Dermatoglyphics In Myocardial Infarction

Introduction: Dermatoglyphics pattern is feature with which human takes birth. As a diagnostic aid, it is now well established in a number of diseases which have a strong hereditary basis. The aetiology of coronary heart diseases is believed to be multi-factorial with genetics playing an important role. Objective: The present study was designed to make an observation of the usefulness of dermatoglyphic pattern in serving as a predictor for myocardial infarction among Bangladeshi male who were non relative to each other. Place of study: The study was conducted in the Department of Anatomy, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, between October 2003 and February 2005. Method: Inking method was used for taking finger and palm prints. Dermatoglyphic prints of five fingers and palm of both hands of sixty individuals were collected. Of them dermatoglyphic prints of both hands of 30 myocardial infarction (MI) male patients non relative to each other were selected as patients and same of 30 normal male having no myocardial infarction and having no family history of MI were selected as control. The dermatoglyphics of each hand of the patients were compared with those of the controls for: a) frequencies of different finger ridge patterns of the five fingers; b) total finger ridge count (TFRC); c) a-b, b-c, and c-d ridge counts of each hand; d) a-t-d angle; e) frequency of palmar ridge pattern and f) frequencies of different palmar creases. Result: The results of the controls confirmed more or less to the ethnic trends of the normal Bangladeshi. In case of finger dermatoglyphics, the MI patients showed higher frequencies of whorl patterns but lower frequencies of ulnar loop, radial loop and arch patterns than the controls. The mean total finger ridge count of the MI patients was lower than that of the controls (p&gt;0.05). In case of palmar dermatoglyphics a-b, c-d ridge counts was higher and b-c ridge counts was lower in the MI patients than in the controls. Mean a-t-d angle was wider in the MI patients than that of the controls. Palmar patterns and creases showed no significant difference except transitional crease of the right hand that was significantly lower in MI patients than controls. Conclusion: Result of this study may be used to standardize the dermatoglyphic pattern of Bangladeshi population and to identify person susceptible to MI. DOI: http://dx.doi.org/10.3329/jafmc.v7i2.10386 JAFMC 2011; 7(2): 4-8

Abstract MP034: Adiponectin Concentrations are Inversely Associated with Risk of Peripheral Arterial Disease in Men

Background: Lower concentrations of adiponectin have been linked to the development of occlusive coronary events in otherwise healthy individuals. Whether similar relationships exist for the development of systemic atherosclerosis, such as peripheral arterial disease (PAD), is unknown. Methods: We used data from a prospective, nested case-control study among 18,225 male participants of the Health Professionals Follow-up Study aged 40 to 75 years who were free of diagnosed cardiovascular disease at the time of blood draw (1993–1995). During 14 years of follow-up through January 31, 2008, 143 men developed PAD. Using risk set sampling, controls were selected in a 3:1 ratio matched for age, date of blood draw, fasting status and smoking status (n=429). We used conditional logistic regression models to assess PAD risk. Results: Higher adiponectin concentrations were associated with a lower risk of PAD (Odds ratio [OR] per SD increase 0.58; 95% confidence interval [CI], 0.45–0.75) after controlling for pack-years of smoking, type 2 diabetes, hypertension, family history of myocardial infarction, aspirin use, body mass index and physical activity. Additional adjustment for low- and high-density lipoprotein cholesterol and high-sensitivity C-reactive protein concentrations attenuated the association (OR per SD increase, 0.71; 95% CI, 0.54–0.95). Further adjustment for hemoglobin A 1c , triglyceride, and gamma-glutamyltransferase concentrations did not alter the results. A log-linear inverse dose-response relationship was evident over the full spectrum of total adiponectin concentrations ( P trend =0.02; Figure). Conclusion: Total adiponectin concentrations are inversely associated with risk of PAD in otherwise healthy men. This relationship can only partly be explained by cholesterol and C-reactive protein concentrations and is independent of triglycerides and glycemic status. Figure legend: Dose-Response Relationship between Total Adiponectin Concentrations and Odds Ratio of PAD.

Abstract P251: The Impact of Clinical Risk Factors on Risk of Peripheral Arterial Disease in Men

Background: Previous studies have examined individual risk factors in relation to peripheral arterial disease (PAD) but the combined effects of these factors are largely unknown. We investigated the degree to which clinical risk factors may explain the risk of PAD among men. Methods: We prospectively followed 45,596 men from the Health Professional Follow-up Study without a history of cardiovascular disease at baseline during a 22-year period (1986–2008). We defined four clinical risk factors - smoking, history of type 2 diabetes, hypertension, and hypercholesterolemia - that were updated biennially during follow-up. Cox proportional hazard models were used to compare PAD risk across individual and joint risk factors. Results: During 874,769 person-years of follow-up, 497 confirmed PAD cases occurred. All four clinical risk factors were significantly and independently associated with a higher risk of PAD after multivariate adjustment (Figure). Risk of PAD more than doubled (hazard ratio: 2.14; 95% confidence interval [95% CI]: 1.95–2.35) for each additional risk factor compared with the group free of risk factors. Men without any of the four risk factors had a relative risk of PAD of 0.19 compared with all other men (95% CI: 0.11–0.31). In 96.8% (95% CI: 95.2–98.3%) of the PAD cases, at least one of the four risk factors was present. Overall, 8 out of 10 cases of PAD appeared to be attributable to these four conventional risk factors. Conclusion: The great majority of PAD can be explained by four conventional risk factors. Figure legend: Hazard ratios for incident peripheral arterial disease (PAD) according to individual and joint risk factors. Hazard ratios are adjusted for age, height, aspirin use, family history of myocardial infarction before age 60 y, geographical region, body mass index, physical activity, alcohol consumption (and each of the other three binary clinical risk factors in the individual risk factor analyses).

The prevalence of microalbuminuria and relevant cardiovascular risk factors in Turkish hypertensive patients

A growing body of data illustrates the importance of microalbuminuria (MAU) as a strong predictor of cardiovascular risk in the hypertensive population. The present study was designed to define the prevalence of MAU and associated cardiovascular risk factors among Turkish hypertensive outpatients. Representing the Turkish arm of the multinational i-SEARCH study involving 1,750 sites in 26 countries around the world, a total of 1,926 hypertensive patients from different centers were included in this observational and cross-sectional survey study. Patients with reasons for a false-positive MAU test were excluded. The prevalence of MAU was assessed using a dipstick test, and patients were inquired about comorbidities, comedication, and known cardiovascular risk factors. The overall prevalence of MAU was 64.7% and there was no difference between genders. Most of the patients (82.5%) had uncontrolled hypertension, 35.6% had dyslipidemia, and 35.5% had diabetes, predominantly type 2. Almost one-third of the patients (26.4%) had at least one cardiovascular-related comorbidity, with 20.3% having documented coronary artery disease (CAD). Almost all patients (96.8%) had one or more risk factors for cardiovascular disease in addition to hypertension, including family history of myocardial infarction or CAD, diabetes, dyslipidemia, lack of physical exercise, and smoking. A trend towards higher MAU values in the presence of CAD was determined. Microalbuminuria tests should be routinely used as a screening and monitoring tool for the assessment of subsequent cardiovascular morbidity and mortality among hypertensive patients.

Additive Effect of ANRIL and BRAP Polymorphisms on Ankle-Brachial Index in a Taiwanese Population

Genetic variations on chromosome 9p21 have been found to be associated with peripheral artery disease (PAD), but have not been investigated in Asians. The ankle-brachial index (ABI) is a widely-used measurement for PAD. We previously reported the BRAP gene is associated with the ABI, so the aim of the present study was to test whether the ANRIL gene on 9p21 is associated with the ABI and to test an interaction between BRAP and ANRIL in a Chinese population. A total of 745 subjects with a family history of myocardial infarction or stroke were enrolled. The multiplicative and additive effects of 2 significant single-nucleotide polymorphisms (SNPs) were evaluated by multivariable regression analysis. SNP rs2383207 on ANRIL was most significantly associated with lower ABI. Similar to our previous findings, SNP rs11066001 on BRAP was associated with lower ABI. A dose-response relationship between ABI values and the number of risk alleles from the 2 significant SNPs was observed in both men and women (adjusted P=0.004 for men, 0.008 for women). The combined genetic effect on ABI was stronger in smokers than in non-smokers. ANRIL on 9p21 and BRAP were both associated with ABI in a Taiwanese population. An additive effect between variants of these 2 genes was found. The finding of a potential gene-gene interaction and gene-environment interaction is interesting, but needs further investigation.

Erectile dysfunction: a vascular disease in the field of urology

Erectile dysfunction: a vascular disease in the field of urology

Relative Familial Clustering of Cerebral Versus Coronary Ischemic Events

Few population-based studies have ascertained both cerebral and coronary events or considered their relative heritability. Differences in heritability of transient ischemic attack and ischemic stroke versus acute coronary syndromes (ACS) may inform risk prediction, genetic studies, and understanding of disease mechanisms. In a population-based study of all acute vascular events, irrespective of age, we studied family history of myocardial infarction (MI), stroke, and related risk factors in first-degree relatives. To allow for differences in rates of affected first-degree relatives caused by differences in disease incidence, we looked at the extent to which parental history was associated with affected siblings within disease category. Nine hundred six probands (604 men; mean age, 70 years) with ACS and 1015 (484 men; mean age, 73 years) with cerebral events had complete family history data. In ACS probands, parental MI was associated with MI in ≥1 sibling (1 parent with MI: odds ratio, 1.48; 1.04 to 2.10; P=0.03; both parents with MI: odds ratio, 5.97; 3.23 to 11.03; P<0.0001). In probands with cerebral events, however, parental stroke was not associated with sibling stroke. The overall frequency of ≥2 siblings with the same condition was also greater in probands with ACS than in those with cerebral events (odds ratio, 5.43; 3.03 to 9.76; P<0.00001), despite similar overall incidence of MI and stroke in our study population. One hundred forty-two (15.7%) cases of ACS occurred in families with ≥2 affected first-degree relatives compared with 56 (5.1%) transient ischemic attack/strokes. All results were similar when analyses were confined to probands with MI only versus stroke only, and independent of smoking. Heritability of coronary events was greater than that of cerebral events, such that MI was more likely to cluster in families than was stroke.

Constipation and Risk of Cardiovascular Disease among Postmenopausal Women

Background Constipation is common in Western societies, accounting for 2.5 million physician visits/year in the US. Because many factors predisposing to constipation also are risk factors for cardiovascular disease, we hypothesized that constipation may be associated with increased risk of cardiovascular events. Methods We conducted a secondary analysis in 93,676 women enrolled in the observational arm of the Women's Health Initiative. Constipation was evaluated at baseline by a self-administered questionnaire. Estimates of the risk of cardiovascular events (cumulative end point including mortality from coronary heart disease, myocardial infarction, angina, coronary revascularization, stroke, and transient ischemic attack) were derived from Cox proportional hazards models adjusted for demographics, risk factors, and other clinical variables (median follow-up 6.9 years). Results The analysis included 73,047 women. Constipation was associated with increased age, African American and Hispanic descent, smoking, diabetes, high cholesterol, family history of myocardial infarction, hypertension, obesity, lower physical activity levels, lower fiber intake, and depression. Women with moderate and severe constipation experienced more cardiovascular events (14.2 and 19.1 events/1000 person-years, respectively) compared with women with no constipation (9.6/1000 person-years). After adjustment for demographics, risk factors, dietary factors, medications, frailty, and other psychological variables, constipation was no longer associated with an increased risk of cardiovascular events except for the severe constipation group, which had a 23% higher risk of cardiovascular events. Conclusion In postmenopausal women, constipation is a marker for cardiovascular risk factors and increased cardiovascular risk. Because constipation is easily assessed, it may be a helpful tool to identify women with increased cardiovascular risk.

Coronary artery spasm: A quandary

Coronary artery spasm can result in acute coronary syndrome. This vasospastic syndrome can cause profound morbidity and mortality as a significant proportion of patients continue to have angina despite optimal medical therapy. We illustrate the dilemma in managing a young woman who presented with non ST-segment myocardial infarction as a result of it. She did not have the conventional risks for coronary artery disease except the family history of myocardial infarction. Vasospasm was demonstrated at the mid right coronary artery which resolved with intracoronary nitroglycerine during angiogram. Most women with no significant heart disease following demonstration of normal or “near normal” coronary arteries after angiography are offered no treatment beyond reassurance each year. New data suggest that this approach may no longer be appropriate and the prognosis in such patient is not as benign as previously thought. We discuss the management dilemma of such patient with associated mild atherosclerotic plaque.

Plasma fibroblast growth factor 23, parathyroid hormone, phosphorus, and risk of coronary heart disease

Fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and phosphorus all have been proposed as plasma biomarkers for the development of coronary heart disease (CHD) in individuals with normal renal function. In a nested case-control study of men in the Health Professionals Follow-up Study, free of diagnosed cardiovascular disease at blood draw, we prospectively examined associations between plasma FGF23, PTH, and phosphorus and risk of CHD. During 10 years of follow-up, 422 men developed nonfatal myocardial infarction or fatal CHD. Controls were selected in a 2:1 ratio and matched for age, date of blood collection, and smoking status. Mean estimated glomerular filtration rate was 86 mL/min per 1.73 m(2) in cases and controls. At baseline, there were no statistically significant differences between cases and controls in plasma levels of FGF23, PTH, or phosphorus. After adjusting for matching factors, family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, plasma 25-hydroxyvitamin D, and other factors, the odds ratios for incident CHD for participants in the highest, compared with lowest, quartiles were 1.03 (95% CI 0.70-1.52, P for trend 0.84) for FGF23, 1.20 (95% CI 0.82-1.76, P trend 0.99) for PTH, and 0.72 (95% CI 0.51-1.02, P trend 0.13) for phosphorus. Plasma FGF23, PTH, and phosphorus are not associated with the development of incident CHD in men without chronic kidney disease.

Sex Differences in Early Carotid Atherosclerosis (from the Community-Based Gutenberg-Heart Study)

The objectives of this study were to describe gender differences in intima-media thickness (IMT) in a community-based population study and to define normal IMT values for healthy men and women. In total, 4,814 participants (aged 35 to 74 years; 2,433 men, 2,381 women) from the Gutenberg-Heart Study (GHS) were included. IMT was measured at both common carotid arteries using an edge detection system. Median IMT was 0.62 mm (25th percentile 0.55, 75th percentile 0.70) in women and 0.65 mm (25th percentile 0.57, 75th percentile 0.75) in men and was significantly associated with age (p <0.0001). On multivariate analysis, advanced age, smoking, and arterial hypertension were positively associated with higher IMT in men and women. A subgroup of 1,025 subjects without cardiovascular risk factors or previous cardiovascular disease was analyzed to define normal IMT values. Nomograms were calculated according to age and gender. For each age group, IMT >95th percentile was defined as abnormal. In this subgroup, gender differences in IMT became nonsignificant at older ages. At the age of 35 years, IMT was 0.71 mm in men and 0.61 mm in women at the 95th percentile. In comparison, at the age of 74 years, IMT at the 95th percentile was 0.90 mm in men and 0.89 mm in women. In conclusion, men had higher carotid IMT than women, but predictors of early carotid atherosclerosis were similar across genders. In young subjects without cardiovascular risk factors, normal values for IMT were lower in women compared with men. In contrast, in older subjects, gender differences in IMT became nonsignificant.

Smoking, alcohol consumption, physical activity, and family history and the risks of acute myocardial infarction and unstable angina pectoris: a prospective cohort study

BackgroundFew studies investigated the association between smoking, alcohol consumption, or physical activity and the risk of unstable angina pectoris (UAP), while the strength of these associations may differ compared to other coronary diseases such as acute myocardial infarction (AMI). Therefore, we investigated whether the associations of these lifestyle factors with UAP differed from those with AMI. Additionally, we investigated whether these effects differed between subjects with and without a family history of myocardial infarction (MI).MethodsThe CAREMA study consists of 21,148 persons, aged 20-59 years at baseline and randomly sampled from the Maastricht region in 1987-1997. At baseline, all participants completed a self-administered questionnaire. After follow-up of maximally 16.9 years, 420 AMI and 274 UAP incident cases were registered. Incidence rate ratios (RRs) were estimated using Cox proportional hazards models.ResultsFor both diseases, smoking increased the risk while alcohol consumption was associated with a protective effect. Associations with both risk factors were stronger for AMI than UAP, although this difference was only statistically significant for smoking. In men, an inverse association was found with physical activity during leisure time which seemed to be stronger for the risk of UAP than of AMI. On the contrary, physical activity during leisure time was associated with an increased risk of both AMI and UAP in women which seemed to be weaker for UAP than for AMI. Except for occupational physical activity in women, no significant interactions on a multiplicative scale were found between the lifestyle factors and family history of MI. Nevertheless, the highest risks were found in subjects with both a positive family history and the most unfavorable level of the lifestyle factors.ConclusionsThe strength of the associations with the lifestyle factors did not differ between AMI and UAP, except for smoking. Furthermore, the effects of the lifestyle factors on the risk of both coronary diseases were similar for subjects with and without a positive family history.

Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry

BackgroundRecent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI. In the present study, we investigated whether six single nucleotide polymorphisms (SNP) rs1333049, rs1333040, rs10757274, rs2383206, rs10757278, and rs2383207 representing the 9p21.3 locus were associated with the incidence of an acute MI in patients with the main focus on the familial aggregation of the disease.MethodsThe overall cohort consisted of 976 unrelated male patients presenting with an acute coronary syndrome (ACS) with ST-elevated (STEMI) as well as non-ST-elevated myocardial infarction (NSTEMI). Genotyping data of the investigated SNPs were generated and statistically analyzed in comparison to previously published findings of matchable control cohorts.ResultsStatistical evaluation confirmed a highly significant association of all analyzed SNP's with the occurrence of MI (p < 0.0001; OR: 1.621-2.039). When only MI patients with a positive family disposition were comprised in the analysis a much stronger association of the accordant risk alleles with incident disease was found with odds ratios up to 2.769.ConclusionsThe findings in the present study confirmed a strong association of the 9p21.3 locus with MI particularly in patients with a positive family history thereby, emphasizing the pathogenic relevance of this locus as a common genetic cardiovascular risk factor.

Relation of asymmetric dimethylarginine levels with conventional risk score systems in the healthy subjects with positive family history for coronary artery disease

Coronary artery disease is the most common cause of death in Turkey and the world. Asymmetric dimethylarginine is the major inhibitor of nitric oxide synthesis in humans. It has been shown that increased levels of asymmetric dimethylarginine is associated with endothelial dysfunction and increased atherogenesis. In this study, we aimed to investigate whether asymmetric dimethylarginine level is related with conventional risk score systems in subjects who had family history of coronary artery disease. Fifty two subjects within 20-40 years old of whom first degree relatives had myocardial infarction at young ages and 26 age and sex matched control subjects were included in this cross-sectional observational study. Frequency of diabetes, hyperlipidemia, smoking and serum levels of homocysteine, high-sensitive C-reactive protein (hsCRP) and asymmetric dimethylarginine were compared between risk group and control subjects. Relation of asymmetric dimethylarginine level with Framingham and TEKHARF risk scores was also compared. Chi-square and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Fasting serum glucose, triglyceride, high-density lipoprotein, diastolic blood pressure, waist circumference and TEKHARF scores were increased in the subjects who had family history of myocardial infarction. Total cholesterol, low-density lipoprotein, hsCRP, homocysteine, creatinine and Framingham risk score were similar in studied groups . Asymmetric dimethylarginine levels were 0.1 µmol/L higher in the risk group; however this difference could not reach significance (0.7±0.1 µmol/l vs 0.8±0.1 µmol/l; p=0.061). Measurement of serum asymmetric dimethylarginine levels did not reveal utility in defining conventional coronary artery disease risk score systems in cases that had positive family history. Larger studies including patients with different risk tertiles are needed.

Polymorphism of 270 A &gt; G in BRAP is Associated with Lower Ankle-Brachial Index in a Taiwanese Population

The single nucleotide polymorphism (SNP) rs11066001 of BRAP has been shown to be associated with myocardial infarction (MI), coronary atherosclerosis and carotid atherosclerosis, but it is not clear whether it also plays a role in peripheral artery disease (PAD). The ankle-brachial index (ABI) is often used as a non-invasive measure of PAD; therefore, the aim of this study was to test for a relationship between the SNP rs11066001 and ABI. A total of 537 high-risk subjects with a family history of MI or stroke completed a health survey, including a physical examination, blood test and measurement of ABI. Among them, 523 subjects had the genotypes. Association analyses between the genotype of BRAP and ABI were performed by multiple linear and logistic regressions with adjustment for covariates. We found that the GG genotype is significantly associated with a lower ABI value. For the lowest ABI tertile, the GG genotype had an OR of 2.87 (p =0.018) when compared with the middle ABI tertile, and OR of 2.92 (p =0.015) when compared to the highest ABI tertile. Women with the GG genotype had a lower ABI value than men with the same genotype (p =0.012). Accordingly, women carrying this GG risk genotype may have a higher risk for PAD. Our findings provide additional evidence that support the genetic effect of BRAP on diverse cardiovascular phenotypes.