Risk Of Early Myocardial Infarction Research Articles

Where Do We Go From Here?

A compelling body of evidence indicates that rheumatoid arthritis (RA) substantially increases the risk for early myocardial infarction (MI), silent ischemia, and sudden death. This evidence includes a growing literature on the role of inflammation in atherogenesis, population-based and clinical epidemiology studies on cardiovascular disease (CVD) in patients with RA, and a smaller number of randomized trials of antirheumatic drugs, as reviewed in this supplement. 1 Salmon J.E. Roman M.J. Subclinical atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Am J Med. 2008; 121: S3-S8 Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar , 2 Gabriel S.E. Cardiovascular morbidity and mortality in rheumatoid arthritis. Am J Med. 2008; 121: S9-S14 Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar , 3 Wilson P.W.F. Evidence of systemic inflammation and estimation of coronary artery disease risk: a population perspective. Am J Med. 2008; 121: S15-S20 Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar , 4 Libby P. Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med. 2008; 121: S21-S31 Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar RA, therefore, could and should now be considered an independent cardiovascular (CV) risk factor, with an approximate 1.5- to 2.0-fold increase in risk in persons with RA not accounted for by established CV risk factors. The magnitude of risk is similar to that of the established risk factors. This is a clinically important issue for several reasons, as described by Gabriel 2 Gabriel S.E. Cardiovascular morbidity and mortality in rheumatoid arthritis. Am J Med. 2008; 121: S9-S14 Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar in her studies of the Rochester RA cohort. First, she and others emphasize that the excess overall mortality in patients with RA is largely attributable to CV death. Although RA causes chronic symptoms and sometimes leads to disability, it appears that its link to coronary heart disease and congestive heart failure is the mechanism by which it causes premature death. Second, the excess CVD and CV death appear to occur especially at relatively young ages, in the range of 40 to 60 years. Third, the Rochester RA cohort data demonstrate persuasively that, whereas CV mortality has declined remarkably since the late 1960s, patients with RA have not shared in this decline, and, despite all the advances in risk factor management and acute and long-term cardiologic care, these patients have the same CV mortality rates as they did in the 1960s. The association of RA with silent ischemia and sudden cardiac death, and its curious reduced rate of angina pectoris, may explain why CV mortality rates seem to have been resistant to advances in CV mortality reduction. The apparent increase in MI risk in the setting of a reduced degree of atherosclerosis provides a mechanism for this observation, suggesting that patients with RA more frequently have unstable atherosclerotic plaques compared with non-RA patients.

ENPP1 K121Q Polymorphism is not Related to Type 2 Diabetes Mellitus, Features of Metabolic Syndrome, and Diabetic Cardiovascular Complications in a Chinese Population

Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) is known to influence insulin sensitivity by inhibiting insulin receptor signaling. A DNA polymorphism in the ENPP1 gene at exon 4 (K121Q) was demonstrated to be associated with insulin resistance, type 2 diabetes mellitus (T2DM), and a risk of early myocardial infarction, albeit with controversy. Our aim was to investigate any association of ENPP1 K121Q alleles with T2DM, features of the metabolic syndrome, and diabetic cardiovascular complications in a Chinese population of Han origin. The ENPP1 K121Q polymorphism was determined by a restriction fragment-length polymorphism-polymerase chain reaction in 1,862 patients with T2DM and 844 non-diabetic subjects. The genotype distributions or Q-allele frequency were not statistically different between the diabetic and non-diabetic groups. The anthropometric parameters, systolic and diastolic blood pressures, lipid profiles, and serum creatinine levels of subjects with different ENPP1 K121Q polymorphisms were not statistically different in the two groups or even in the pooled data. When sub-group analyses of diabetic subjects were stratified according to BMI levels (greater or less than 27), gender, age of diabetes onset (older or younger than 60 years), and the presence or absence of a diabetic family history; this polymorphism was still not associated with T2DM. Nor was the ENPP1 K121Q polymorphism associated with the prevalence of coronary artery disease and ischemic cerebrovascular disease in patients with T2DM. The ENPP1 K121Q polymorphism is not related to T2DM, features of the metabolic syndrome, or diabetic macrovascular complications in a Chinese population.

Variation in the lipoprotein receptor-related protein, alpha2-macroglobulin and lipoprotein receptor-associated protein genes in relation to plasma lipid levels and risk of early myocardial infarction.

The lipoprotein receptor-related protein (LRP) is an endocytic receptor for several ligands, such as alpha2-macroglobulin (alpha2 M) and apolipoprotein E. LRP is involved in the clearance of lipids from the bloodstream and is expressed in the atherosclerotic plaque. The LRP-associated protein (LRPAP in humans, RAP in mice) acts as a chaperone protein, stabilizing the nascent LRP peptide in the endoplasmic reticulum and Golgi complex. In mice, the amount of LRP activity was modulated by RAP, and RAP-null mice showed higher levels of total cholesterol. To evaluate the association between DNA polymorphisms at the LRP, LRPAP and alpha2 M genes and early myocardial infarction (MI). We genotyped 210 patients with early MI (<55 years) and 200 healthy control participants for three polymorphisms in the LRP, LRPAP and alpha2 M genes. No association was found between these polymorphisms and plasma lipid levels in patients and control participants. Only the LRPAP-intron 1 polymorphism (a 21 bp insertion/deletion) was associated with MI (P = 0.0065; odds ratio = 2.18, 95% confidence intervals = 1.22-3.90). According to our data, the variation at the LRPAP1 gene could contribute to the risk of developing an early episode of MI.

Связь полиморфизма генов ренин-ангиотензиновой системы и гена эндотелиальной NO-синтазы с макрососудистыми осложнениями сахарного диабета типа 2

The insertion/deletion (I/D) polymorphism of angiotensin 1-converting enzyme (ACE) gene, T174M (threonine substitution for methionine in position 174 of amino acid sequence) polymorphism of angiotensinogen (AGT) gene, A1166C polymorphism of angiotensin II vascular (type 1) receptor (AT1R) gene, and ecNOS4a/4b polymorphism of endothelial N О synthase (NOS3) gene were studied by the polymerase chain reaction (PCR) in patients with type 2 diabetes mellitus and arterial hypertension uncomplicated (control, n = 52) and complicated with cardiovascular diseases (myocardial infarction, n = 53, and acute cerebrovascular disorders, n = 50). Protective effect of 1/1 genotype on development of myocardial infarction in diabetics was shown. The absence of significant differences in the distribution of alleles and genotypes of A GT gene in three groups of patients indicates that this gene is hardly involved in the formation of cardiovascular complications in type 2 diabetes. A strong association between A1166C polymorphism of AT1R gene and development of myocardial infarction in patients with type 2 diabetes and essential hypertension of the Moscow population was revealed; allele A and genotype AA attenuate the risk of early myocardial infarction, while allele C and genotype CC enhance it. A relationship between minisatellite ecNOS4a/4b polymorphism of NOS3 gene and cardiovascular diseases was detected in patients with type 2 diabetes and essential hypertension. Allele 4a and genotypes 4a/4b and 4a/4a are pronounced risk markers, and allele 4b and genotype 4b/4b carriership is associated with a low risk of this complication.

Family history as a risk factor for early onset myocardial infarction in young women

Background: The relation between a family history of heart attack and the occurrence of early myocardial infarction (MI) has not been studied extensively in women. In addition, whether recognized and newly-identified coronary heart disease (CHD) risk factors account for the familial aggregation of these events remains unknown. We therefore examined these questions in a population-based case–control study among female 18- to 44-year-old residents of western Washington State. Methods and results: The patients consisted of 107 women with first acute MI, and the control subjects comprised 526 women similar in age identified from the community and without a history of recognized clinical coronary heart disease or stroke. Trained interviewers used a structured questionnaire to elicit a detailed history of heart attack in first-degree relatives. Information about other known MI risk factors was collected and biochemical measurements performed, and common polymorphisms in various candidate genes were determined. The rate of MI among first-degree relatives of MI cases was twice as high as among first-degree relatives of controls (relative risk, 1.96; 95% confidence interval (CI), 1.46–2.48); this association was present for each familial relationship. Sibling history of MI but not parental history was associated with MI, after controlling for established CHD risk factors. In a subsample of subjects with blood measurements, further adjustment for lipids, lipoproteins and specific genetic risk factors slightly reduced the association with sibling MI history (from odds ratio (OR), 5.17; 95% CI, 1.93–13.85 to OR, 3.97; 95% CI, 0.92–17.17). Conclusion: Family history of MI is positively associated with the risk of early MI in women. While the association with parental history of MI is mediated through the clustering of other common risk factors, the association of sibling history of MI with early-onset MI in young women is only partially explained by the clustering of established and newly-identified risk factors.

Familial dyslipidemic hypertension syndrome: familial combined hyperlipidemia, and the role of abdominal fat mass

Familial combined hyperlipidemia (FCHL) is the most frequent genetic lipid abnormality in humans, with a 5- to 10-fold increased risk of early myocardial infarction. Familial combined hyperlipidemia has been proposed as the leading cause of dyslipidemia in familial dyslipidemic hypertension (FDH). It was the objective of this study to quantify and analyze the simultaneous occurrence of hypertension and hyperlipidemia in FCHL families. We assessed blood pressure (BP) and hyperlipidemia in 27 families with FCHL (235 relatives and 140 spouses, aged 30 to 60 years). Hypertension was defined as a BP more than 140/90 mm Hg, or the use of antihypertensive medication. Multiple backward linear regression analysis was used to derive a biological formula describing BP in FCHL families. One-third of 27 FCHL families were diagnosed with FDH. Sixty-four of 235 (27.2%) relatives had dyslipidemic hypertension (DH), compared to 20 of 140 (14.3%) spouses ( P = .005); odds ratio = 2.25 (95% confidence interval 1.29–3.91). Multiple linear regression analysis showed that age, FCHL status, and waist circumference significantly contributed to systolic blood pressure (SBP) in female FCHL relatives. In conclusion, in FCHL we defined age, waist circumference, and hyperlipidemia as predictors of SBP. This study indicates that visceral adipose tissue strongly contributes to the high prevalence of DH in FCHL families. Reduction of visceral fat should be tested as a potential therapeutic intervention for hyperlipidemia and hypertension in FCHL individuals.

Synergistic Effect between Apolipoprotein E and Angiotensinogen Gene Polymorphisms in the Risk for Early Myocardial Infarction

Several studies based on different populations worldwide have described an association between cardiovascular diseases and genetic variations in the apolipoprotein E (A:POE), angiotensinogen (A:GT), angiotensin receptor type 1 (A:T1R), and angiotensin-converting enzyme (A:CE) genes. In addition, there is growing evidence of an interaction between hypercholesterolemia and the renin-angiotensin system in the risk for hypertension and atherosclerosis. To determine whether the DNA polymorphisms in A:POE (epsilon2, epsilon3, and epsilon4 alleles), A:GT (M235T), A:T1R (1166 A:/C:), and ACE (I:/D:) are associated with early onset of myocardial infarction (MI), we genotyped 220 patients and 200 controls <55 years of age. Patients and controls were males from the same homogeneous Caucasian population. Data concerning hypertension, diabetes, and tobacco consumption were recorded. The lipid profiles of patients and controls were also determined. APOE, ACE, AGT, and AT1R allele and genotype frequencies did not differ between patients and controls. None of these polymorphisms was related to the biochemical values in patients or controls. The frequency of individuals who were both APOE epsilon4 allele carriers and AGT-TT homozygotes was significantly higher in patients than in controls (11% vs 3.5%; P: = 0.0037). In patients, the frequency of epsilon4 carriers was significantly higher (P: <0.00001) in those who were AGT-TT (46%) than those who were AGT-MT/MM (14%). Mean cholesterol was significantly higher in AGT-TT + APOE epsilon34/44 patients than in the TM/MM + epsilon34/44 or TT + epsilon23/33 genotypes (P: = 0. 029). Our data suggest a synergistic effect between the APOE and AGT polymorphisms and early MI. The increased risk could be mediated in part through higher cholesterol concentrations among individuals who are AGT-TT + APOE epsilon4 allele carriers.