Genetic polymorphisms and the risk of myocardial infarction in patients under 45 years of age.
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ABSTRACT:
SUBMITTER: Sakowicz A
PROVIDER: S-EPMC3599159 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveLow levels of physical activity in childhood are associated with clustering of cardiovascular risk factors (CVRF) as predisposition for atherosclerosis. We assessed the association between sports engagement and age at first myocardial infarction (MI) in a cohort of men under 55 years of age.MethodsThe Bern percutaneous coronary intervention Registry (NCT 02241291) was analyzed from March 2009 until January 2012. Male patients with first MI, age 18 to 54 years and body mass index ?25kg/m2 were included. Patients were stratified into two groups based on their starting age with organized sports ?1 h/week outside school (EARLY: <18, CONTROL: ?18 years or never). We assessed age at time of first MI, CVRF, and volume of sports training.ResultsOf 4,394 consecutive patients, 123 fulfilled the inclusion criteria (EARLY n = 81, CONTROL n = 42). Age at the time of first MI was 3 years younger in the EARLY compared to the CONTROL group (46.8±6.0 vs. 49.8±4.6 years, p = 0.006). Total lifetime training hours, and average yearly training hours, both, before and after age 18, were significantly greater in the EARLY group. Years of training <18 years were weakly inversely correlated with age at first MI (r2 = 0.075, p = 0.002). The proportion of sports-related MI was not different between EARLY and CONTROL (13.6% vs. 11.9%). Patients in the EARLY group had fewer CVRF (2 vs. 3; p = 0.001). Prevalence of smoking was equally high in both groups (63.0% and 64.3%).ConclusionsIn our patients aged 54 and younger, the first MI occurred 3 years earlier in those who started regular sports activity before age 18, despite a more active lifestyle and favorable CVRF profile.
| S-EPMC5608204 | biostudies-literature
Project description:Background & objectives:Cytochrome P450, P2Y 12, cyclooxygenase-1 (COX1) and glycoprotein V1 (GPVI) gene polymorphisms are known to affect patient responsiveness towards aspirin and clopidogrel dual antiplatelet therapy (DAPT). The present study was undertaken to identify aspirin and clopidogrel non-responsiveness and its association with genetic polymorphism in patients with myocardial infarction (MI). Methods:A total of 207 MI patients who were on DAPT, were included. The DAPT non-responsiveness was determined by light transmittance aggregometry using arachidonic acid and adenosine diphosphate and high platelet reactivity by collagen. Platelet activation biomarkers, thromboxane B2 (TxB2)andsoluble CD40 ligand (sCD40L) were measured in plasma. Patient compliance was checked by estimating drug and its metabolite levels (aspirin and clopidogrel) in plasma using liquid chromatography-mass spectrometry/mass spectrometry. Genomic DNA was extracted, amplified by polymerase chain reaction and subsequently sequenced to identify CYP450, P2Y 12, COX1 and GPVI gene polymorphisms. Results:Of the 207 patients, 32 were non-responders. The DAPT non-responsiveness was found in 15.5 per cent patients. The non-responsiveness showed a significant and an independent association with gender [odds ratio (OR)=0.18, 95% confidence interval (CI)=0.01-0.78, P=0.023], TxB2(OR=1.00, 95% CI=1.00-1.01, P=0.013), CYP2C19*2 G>A (OR=3.33, 95% CI=1.04-10.69, P=0.044) and GPVI T>C (OR=0.23, 95% CI=0.08-0.67, P=0.007) after adjusting the demographic, clinical and genetic confounding factors when assessed between non-responder and responder compliant patients. Interpretation & conclusions:The study showed a significant association of genetic polymorphisms (CYP2C19*2 G>A and GPVI T>C) with DAPT non-responsiveness in MI patients. The findings of this study need further validation in a large cohort of patients with clinical follow up.
| S-EPMC6798616 | biostudies-literature
Project description:We identified 7 CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001). The inclusion criteria for enrolling patients were drawn from the Prospective Cardiovascular Munster study [http://www.ncbi.nlm.nih.gov/pubmed/3202078] and Framingham Heart Study [http://www.ncbi.nlm.nih.gov/pubmed/9737513]. In brief, patients aged between 20 and 75 years with coronary arterial disease with more than 50% stenosis, as proven by cardiac catheterization, and a history of hyperlipidemia with serum cholesterol level greater than 240 mg/dL or low-density lipoprotein greater than 155 mg/dL were enrolled. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from whole blood samples. 40 Samples.
2014-08-09 | E-GEOD-31276 | biostudies-arrayexpress
Project description:To determine the degree of risk factor control, the clinical symptoms and the therapeutic management of patients with a history of previous myocardial infarction.Cross-sectional study at 6 years of a first episode of acute myocardial infarction between 2000 and 2009, admitted at a hospital in the region of Extremadura (Spain). Of 2177 patients with this diagnosis, 1365 remained alive and therefore were included in the study.We conducted a person-to-person survey in 666 (48.8%) individuals and telephone survey in 437 (31.9%) individuals. The former are analysed. 130 were female (19.5%). The mean age was 67.4 years and the median time since the event was 5.8 (IQR 3.6-8.2) years. Active smokers made up 13.8%, low-density lipoprotein (LDL) cholesterol was ≥70 mg/dL: 82%, blood pressure ≥140/90 mm Hg (≥140/85 in diabetics): 49.8%, fasting glucose ≥126 mg/dL: 26%, heart rate 50-59 bpm: 60.7%, and obesity: 45.9%. Patients reported presenting angina comprised 22.4% and those with dyspnoea, 29.3%. Drug coverage was: 88.0% antiplatelet drugs, 86.5% statins, 75.6% β-blockers and 65.8% blockers of the renin-angiotensin system. Patients receiving all four types of drugs made up 41.9%, with only 3.0% having jointly controlled cholesterol, blood pressure, heart rate and glycaemia.LDL cholesterol, heart rate and blood pressure were risk factors with less control. More than 1/5 of patients had angina and more than 1/4, dyspnoea. Risk factor control and the clinical condition were far from optimal, as was drug coverage, although to a lesser degree.
| S-EPMC4847157 | biostudies-other
Project description:We identified 7 CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001). The inclusion criteria for enrolling patients were drawn from the Prospective Cardiovascular Munster study [http://www.ncbi.nlm.nih.gov/pubmed/3202078] and Framingham Heart Study [http://www.ncbi.nlm.nih.gov/pubmed/9737513]. In brief, patients aged between 20 and 75 years with coronary arterial disease with more than 50% stenosis, as proven by cardiac catheterization, and a history of hyperlipidemia with serum cholesterol level greater than 240 mg/dL or low-density lipoprotein greater than 155 mg/dL were enrolled.
2014-08-09 | GSE31276 | GEO
Project description:Postacute myocardial infarction (AMI) readmissions are common among Medicare beneficiaries (≥65 years) and are associated with significant resource utilization. However, patterns of AMI readmissions for younger age groups in the United States are not known. In the Nationwide Readmissions Database, a nationally representative all-payer database of inpatient hospitalizations, we identified 212,171 index AMI hospitalizations in January to November 2013, weighted to represent 478,247 hospitalizations nationally (mean age 66.9 years, 38% women, 29% low income). This included 26,516 cases in the 18 to 44 age group, 183,703 in the 45 to 64 age group, and 268,027 in the ≥65 age group. The overall 30-day readmission rate was 14.5% and varied across age groups (9.7% [18 to 44], 11.2% [45 to 64], and 17.3% [≥65]). The cumulative cost of 30-day readmissions was $1.1 billion, of which $365 million was spent on those <65 years of age. In multivariable hierarchical models, the risk of readmission was higher in women and in low-income patients, but the effect varied by age (p value for age-gender and age-income interactions <0.05) and was more prominent in the younger age groups. Further, patients in all age groups continue to have a high hospitalization burden beyond the typical 30-day readmission period, with an overall 24% post-AMI 90-day readmission rate. In conclusion, readmissions in young and middle-aged AMI survivors pose a substantial burden on patients and on U.S. health-care resources. Women and low-income patients with AMI, particularly those in younger age groups, are more frequently readmitted, and readmissions continue to burden the health-care system beyond the typical 30-day window. Future investigations would need to be targeted toward a better understanding and improvement of the rehospitalization burden for vulnerable patient groups.
| S-EPMC5825232 | biostudies-literature
Project description:BackgroundGenome-wide association studies have identified loci associated with coronary heart disease in whites of European ancestry. This study evaluated whether genetic markers previously identified in whites are associated with nonfatal acute myocardial infarction (MI) in Hispanics.Methods and resultsCases (n=1989) with a first nonfatal acute MI and population-based controls (n=2096) living in Costa Rica were studied. Fourteen single-nucleotide polymorphisms were genotyped. Seven single-nucleotide polymorphisms at 3 independent loci showed significant associations with MI. The odds ratios for the loci with the strongest associations were 1.16 (95 confidence interval [CI], 1.05 to 1.27) for rs4977574 (CDKN2A/2B), 1.15 (95 CI, 1.03 to 1.29) for rs646776 (CELSR2-PSRC1-SORT1), and 1.22 (95 CI, 1.08 to 1.38) for rs501120 (CXCL12); the corresponding PARs were 6.8, 10.5, and 15.2; respectively. We developed a genetic risk score by summing the number of the top 3 associated risk alleles. The OR for MI per genetic risk score unit was 1.18 (95 CI, 1.11 to 1.25; P=4.83 × 10(-8)). Discrimination of MI was significantly improved (P=0.02) when the genetic risk score was added to a model including clinical predictors. However, the increase in the area under the receiver-operating characteristic curve after the genetic risk score was added was moderate, from 0.67 (95 CI, 0.65 to 0.69) to 0.68 (95 CI, 0.66 to 0.70).ConclusionsThese results indicate both the consistency and disparity of genetic effects on risk of MI between Hispanic and white populations. The improvement in the identified genetic markers on discrimination of MI in Hispanics was modest.
| S-EPMC3076095 | biostudies-literature
Project description:BackgroundThe incidences of premature coronary heart disease present a rising trend worldwide. The possible risk factors that may predict the incidence of repeat percutaneous coronary intervention (PCI) in premature acute coronary syndrome (ACS) remains unclear.MethodsA total of 203 patients ≤45 years with ACS from Chinese PLA General Hospital who have undergone angiography twice were included in this report. Data were collected from medical records of patients during hospitalization. Baseline characteristics which have significant differences in the univariate analysis were enrolled into the multiple logistic regression analysis. According to the odds ratio (OR) of these variables, different values were assigned to build a risk model to predict the possible risk of the premature ACS patients undergoing repeat PCI.ResultsOf the 203 young patients, 88 patients (43.3%) underwent repeat PCI. The intermit time (OR 1.002, (95% CI [1.001-1.002])), diastolic blood pressure of second procedure (OR 0.967, (95% CI [0.938-0.996])), stent diameter (OR 0.352, (95% CI [0.148-0.840])), HbA1C of the first procedure (OR 1.835, (95% CI [1.358-2.479])), and Troponin T of the second procedure (OR 1.24, (95% CI [0.981-1.489])) were significantly associated with the incidence of repeat PCI in patients with premature ACS. An aggregate score between 0 and 6 was calculated based on these cutpoints.ConclusionFor young patients with premature ACS, risk of undergoing repeat PCI was high. HbA1C was a significant, independent predictor for the incidence of repeat revascularization, and weighed more than traditional lipid profile. The glucose metabolism and disorders in patients with premature ACS should be routinely screened.
| S-EPMC6487803 | biostudies-literature
Project description:Aims:This study was aimed to determine the levels of hs-CRP, serum ferritin, and Lp(a) and to study the prevalence of metabolic syndrome (MetS) in young patients (?45 years) with and without acute myocardial infarction (AMI). Methods:This was a cross-sectional, case-control study conducted at a tertiary care center in India. Equal number of patients with matched age and sex (n?=?51) were included in case group (with AMI) and in control group (without AMI). Subjects were assessed for the presence of MetS as per modified ATP III criteria. The hs-CRP, Lp(a), and serum ferritin were also measured. Results:The prevalence of MetS was found to be 62.74% in case group, whereas 33.33% in control group with decreased HDL level as the most prevalent parameter. The hs-CRP level was found to be 15.35?±?8.27 mg/dl in case group and 1.85?±?1.05 mg/dl in control group and Lp(a) was 33.84?±?23.69 mg/dl in case group and 19.68?±?10.39 mg/dl in control group. No significant difference was observed in the serum ferritin level in case (264.2?±?40.6 ng/dl) and control (225.51?±?45.35 ng/dl) groups. Conclusion:From this study, we can conclude that the assessment of these novel risk factors [hs-CRP, Lp(a), and MetS] may be used for the risk estimation and can help to prevent future mortality and morbidity due to CVD.
| S-EPMC6167620 | biostudies-other
Project description:The studied group comprises 124 patients with acute myocardial infarction on dual antiplatelet therapy with acetylsalicylic acid (ASA) and thienopyridines. Antiplatelet therapy was monitored by platelet-rich plasma light transmittance aggregometry (LTA) using the APACT 4004 analyzer (Helena Laboratories) and by whole blood impedance aggregometry (multiple electrode aggregometry [MEA]) using the Multiplate analyzer (Dynabyte). Platelet aggregation was detected after stimulation with arachidonic acid for detection of aspirin resistance and with adenosine diphosphate (ADP) and prostaglandin E1 for detection of thienopyridine resistance. To determine the frequencies of P2Y12 (i-744T>C; rs2046934), P2Y12 (34C>T; rs6785930), COX-1 (-842A>G; rs10306114), GPVI (13254T>C; rs1613662), and GPIbA (5T>C; rs2243093) polymorphisms, DNA of patients with AIM was tested by real-time-polymerase chain reaction and melting curve analysis using the LightCycler 480 analyzer (Roche Diagnostics).The cut-off points used for patients with effective ASA therapy are 25% of aggregated platelets and 220 area under the curve (AUC)/min if LTA or MEA, respectively. The cut-off points used for effective thienopyridine therapy are 45% of aggregated platelets or 298 AUC/min, respectively. Both LTA and MEA found that aspirin and thienopyridine therapies failed in 14.51% and 25.8%, respectively. The data were statistically processed using the SPSS version 15 software (SPSS, Inc.). Associations between receptor mutation status and response to therapy were assessed with Fisher's exact test. The significance level was set at 0.05.The aim of our work was to use the two functional laboratory methods described earlier to assess both aspirin and thienopyridine resistance and to determine the contribution of genetic polymorphisms of platelet receptors to resistance to antiplatelet therapy in AIM. Fisher's exact test showed a significant statistical correlation between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of COX1_A1 (-A842G). Fisher's exact test showed no statistically significant correlations between platelet function tests suitable for monitoring ASA resistance, that is, LTA and MEA, and mutation status of GP1bA (-5T>C) and GP6 (T13254C). Fisher's exact test showed no statistically significant correlation between mutational statuses of the receptors P2RY12 (i-T744C), P2RY12 (C34T), GP1bA (-5T>C), or GP6 (T13254C) and response to antiplatelet therapy with 75?mg of clopidogrel.
| S-EPMC4150366 | biostudies-literature