Interleukin 18 gene variation and risk of acute myocardial infarction

Interleukin 18 is an important mediator of inflammation and has been associated with the development and aggravation of cardiovascular diseases. We report that common variation in the interleukin 18 gene is related to acute myocardial infarction, a frequent clinical manifestation of atherosclerosis and thrombosis in coronary arteries. In a population of European, mainly (90%) German, ancestry (2136 cases with acute myocardial infarction and 1211 controls), the association was based on specific alleles and haplotypes derived from a set of six tagging single nucleotide polymorphisms. The rs1946519-G (located in the 5' upstream region), rs360717-C (exon 1), rs5744241-G (intron 1), rs1834481-C (intron 3), and rs3882891-A (intron 5) alleles (P≤0.039) and a haplotype (GCGCAG haplotype; P=0.0028) containing the GCGCA motif derived from these alleles were associated with an increased risk of AMI. Corresponding with this result, the complementary alleles (rs1946519-T, rs360717-T, rs5744241-A, rs1834481-G, and rs3882891-C) and a haplotype (TTAGCG haplotype; P=0.018) with the TTAGC motif showed protective effects. Haplotypes not including the GCGCA or TTAGC motif were not related to AMI (P≥0.22). These observations suggest that the interleukin 18 gene is a susceptibility locus for acute myocardial infarction, a finding of potential interest in the clinical practice.     

Antibodies against oxidation-specific epitopes and risk of acute myocardial infarction

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HindIII polymorphism of lipoprotein lipase gene and risk of myocardial infarction

The purpose of this study was to determine whether HindIII restriction polymorphism found in intron 8 of lipoprotein lipase gene is associated with the onset of myocardial infarction (MI) in Russians and Tartars living in Bashkortostan. HindIII polymorphism was investigated by the polymerase chain reaction in myocardial infarction survivors (males aged under 55 years (98 Russians and 68 Tartars) and in controls (53 Russians and 80 Tartars). The distribution of genotypes and allele frequencies in the controls were as follows: the frequencies of genotypes HindIII(-/-), HindIII(+/-), and HindIII(+/+) in Russians (3.77, 49.06, and 47.17%, respectively) did not differ from those in Tartars (7.50, 51.24, and 41.25%, respectively), while the frequency of HindIII(-) allele was 28.30% in Russians and 33.13% in Tartars. Among Tartars, the HindIII(+/+) genotype was more common in myocardial infarction survivors than in controls (OR 2.03). In the Russians this genotype was not associated with the risk of MI. The frequencies of HindIII(+/+) genotype and allele HindIII(+) were significantly higher (OR 8.96 and 6.71, respectively) and frequencies of HindIII(+/-) genotype and allele HindIII(-) were lower (OR 0.13 and 0.15) in Russian patients with repeated MI. These findings indicate that HindIII polymorphism may be a genetic risk factor for MI before 55 years of age in the Tartars and for repeated MI in Russians. This association prompts genotyping of HindIII polymorphism for predicting MI recurrence in Russian survivors after MI.     

Association between inflammatory gene polymorphisms and the risk of myocardial infarction

Allele and genotype frequency distributions of polymorphism rs2076059 (3832T>C) within the SELE gene, rs6131 (S290N), within the SELP gene, rs1131498 (F206L), within the SELL gene, rs5498 (K469E) within the ICAM1 gene, rs35569394 (?2549(18)I/D) within the VEGFA gene, and rs1024611 (?2518A>G) within the CCL2 gene were examined in a group of patients after myocardial infarction (MI)(280 individuals) and in a control group (312 individuals). An implementation of the Markov chain and Monte-Carlo method (APSampler) revealed the allele combinations associated with decreased and increased risk of MI. Among these, the most important allele combinations were SELE*C + SELP*S + CCL2*A (FDR = 0.0005; OR = 0.42), SELP*S + CCL2*A (FDR = 0.0009; OR = 0.36), SELL*F + VEGFA*I + CCL2*G/G (FDR = 0.0009; OR = 4.17), VEGFA*I + CCL2*G/G (FDR = 0.0009; OR = 3.76), SELE*C + CCL2*A (FDR = 0.0023; OR = 0.47), and SELL*F + CCL2*G/G (FDR = 0.003; OR = 3.15).     

Pneumococcal polysaccharide vaccination in rheumatoid arthritis patients receiving tacrolimus

IntroductionIn rheumatoid arthritis (RA) patients receiving immunosuppressive treatments, vaccination against Streptococcus pneumoniae is recommended. The objective of the study was to evaluate the effects of tacrolimus (TAC) on immune response following administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) in patients with established RA.MethodsPatients with RA (n = 133) were vaccinated with PPSV23. Patients were classified into TAC (n = 29), methotrexate (MTX) (n = 55), control (n = 35), and TAC/MTX (n = 14) treatment groups. We measured the concentrations of pneumococcal serotypes 6B and 23F by using an enzyme-linked immunosorbent assay and determined antibody functionality by using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI), before and 4 to 6 weeks after vaccination. A positive antibody response was defined as at least a twofold increase in the IgG concentration or as at least a 10-fold increase in the OI.ResultsIgG concentrations and OIs were significantly increased in all treatment groups after PPSV23 vaccination. The TAC treatment group appears to respond in a manner similar to that of the RA control group in terms of 6B and 23F serotype concentration and function. In contrast, the MTX group had the lowest immune response. Patients who received a combination of TAC and MTX (TAC/MTX) also had a diminished immune response compared with those who received TAC alone.ConclusionsTAC monotherapy does not appear to impair PPSV23 immunogenicity in patients with RA, whereas antibody production and function may be reduced when TAC is used with MTX. Thus, PPSV23 administration during ongoing TAC treatment should be encouraged for infection-prone TAC-treated patients with rheumatic diseases.

Trial registration

University Hospital Medical Information Network Clinical Trials Registry: UMIN000009566. Registered 12 December 2012.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0662-x) contains supplementary material, which is available to authorized users.     

Polymorphism of the apolipoprotein E gene and the risk of myocardial infarction

The apolipoprotein E (ApoE) gene polymorphism resulting from nucleotide substitutions in exon 4 was analyzed in Russian and Tatar patients with myocardial infarction (MI) from Bashkortostan. Alleles epsilon 2, epsilon 3, and epsilon 4 were identified by PCR. The genotype frequency distribution proved to be age-dependent in healthy Russians, genotype E2/3 increasing in frequency in subjects beyond 45. Russians who suffered MI under 45 had lower frequencies of genotype E3/3 (50.00% vs. 75.47% in controls of the same age, P = 0.013, OR = 0.33) and allele epsilon 3 (72.12% vs. 85.85%, P = 0.020, OR = 0.43) and a higher frequency of allele epsilon 4 (22.12% vs. 10.38%, P = 0.030, OR = 2.45). Russians who suffered MI complicated by cardiogenic shock (CS) had a significantly higher frequency of genotype E3/4 and lower frequencies of genotype E3/3 and allele epsilon 3 as compared with MI patients without CS. In Tatars, genotype E4/4 occurred at a frequency of 14.29% in patients who suffered MI under 45, and was not detected in healthy subjects of the same age (P = 0.024, OR = 17.85). Thus, the ApoE polymorphism was associated with higher risk of MI in Russians and Tatars under 45.     

Assessment of cardiac risk 10 days after uncomplicated myocardial infarction.

A total of 188 patients with uncomplicated acute myocardial infarction (long-term Norris prognostic index 3.2) were rapidly mobilised, underwent a symptom-limited exercise test around the day of discharge from hospital (day 10), and returned to work at a median of six weeks after the acute event. The incidence of cardiac death six months, one year, and three years after infarction was 2.7%, 4.5%, and 7.3% respectively, and the corresponding figures for recurrent heart attacks were 3.4%, 8.2%, and 18.5% respectively. The risk of recurrence of heart attack was predicted by three variables assessed at discharge--namely, a history of classical effort angina (p less than 0.01), radiological heart failure (p less than 0.05), and angina induced by the exercise test (p less than 0.05). The presence of any of these risk factors defined a group of patients with a sevenfold risk of recurrent heart attacks within six months of the initial acute infarct. It is concluded that these risk factors identify a group of patients with a high risk of recurrence early after infarction, in whom vigorous secondary prophylaxis is desirable.     

Metabolic syndrome X--high risk factor for acute myocardial infarction and its complications

Metabolic Syndrome X is a clinical entity which comprises the following factors: diabetes mellitus, arterial hypertension, high levels of triglyceride and/or low levels of HDL cholesterol, central obesity and microalbuminuria (by WHO criteria). The first goal of this study was to determine the frequency of the Metabolic Syndrome X (MSX) in patients with acute myocardial infarction compared with the general population. The second goal of the study was to examine the frequency of heart failure and reinfarction rate in the patients with myocardial infarction, with and without MSX. Furthermore, the relationship between gender and MSX was analyzed. A total of 101 patients with acute myocardial infarction took part in randomized trial (32 women and 69 men). MSX and all of its components were diagnosed according to WHO criteria. To determine statistical significance of our results, we used chi2 test and t-test for independent samples. From 101 patient 48 had MSX (47.52%), while in the general population incidence of MSX is 3-4%. The reinfarction and the heart failure rate were significantly higher in the group of patients with MSX (p = 0.0067 and p = 0.0217, respectively). To conclude, the results of the present study confirm that MSX is a high risk factor for myocardial infarction and its complications.     

Growth hormone for risk stratification and effects of therapy in acute myocardial infarction

Abstract

Context: Excess growth hormone (GH) is associated with early mortality.

Objectives: We assessed the association of GH with prognosis after acute myocardial infarction (AMI), and the effects of secondary prevention therapies.

Methods: GH was measured using a high-sensitivity assay in 953 AMI patients (687 males, mean age 66.1?±?12.8 years).

Results: During 2 years follow-up, there were 281 major adverse cardiac events (MACE). Patients with MACE had higher GH levels (median [range], 0.91 [0.04–26.28] μg/L) compared to event-free survivors (0.59 [0.02–21.6], p?<?0.0005). In multivariate Cox survival analysis, GH was a significant predictor of MACE (hazard ratios 1.43, p?=?0.026 and 1.49, p?=?0.01, respectively) with significant interactions with beta blocker therapy (p?=?0.047) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACE/ARB) therapy (p?=?0.016).

Conclusions: GH levels post-AMI are prognostic for MACE and may indicate those patients who benefit from beta blocker and ACE/ARB therapy.     

Tar yield of cigarettes and risk of acute myocardial infarction. GISSI-EFRIM Investigators.

OBJECTIVE--To analyse the relation between tar and nicotine yield of cigarettes smoked in the recent past and the risk of myocardial infarction. DESIGN--Multicentre case-control study conducted between September 1988 and June 1989. SETTING--Over 80 coronary care units in various Italian regions. SUBJECTS--916 patients with acute myocardial infarction without history of ischaemic heart disease and 1106 controls admitted to hospital for acute conditions not related to known or suspected risk factors for ischaemic heart disease. MAIN OUTCOME MEASURES--Relative risk of myocardial infarction according to type of cigarette smoked adjusted for identified potential confounding factors. Brands of cigarettes classified according to yield of tar and nicotine. RESULTS--Patients with acute myocardial infarction were more often smokers and among smokers they tended to smoke more cigarettes. Compared with non-smokers their estimated relative risks were 3.8, 4.3, 3.2, and 3.7 in the four categories of tar yield (< 10, 10-15, > 15-20, and > 20 mg, respectively). No trend in risk across yields was evident when analysis was restricted to smokers and allowance was made for number of cigarettes. Compared with risks in subjects in the lowest category of tar yield the relative risks were 1.2, 0.8, and 1.0 for the subsequent yields. Compared with risks in non-smokers the relative risks ranged from 9.3 to 12.6 below the age of 50 but no trend was observed with increasing yield. CONCLUSIONS--Changing to cigarettes with a lower tar yield is not an effective means of reducing tobacco related morbidity from myocardial infarction.     

Dietary intake of carotenoids and retinol and the risk of acute myocardial infarction in Italy

BACKGROUND: Carotenoids may reduce the risk of coronary heart disease through their antioxidant properties, but the results of epidemiological studies are controversial. We analysed the relation between the intake of selected carotenoids and retinol and risk of acute myocardial infarction (AMI). METHODS: A case-control study was conducted in Milan, Italy, in 1995-2003. Cases were 760 patients with nonfatal AMI, and controls 682 patients admitted to hospital. RESULTS: The risk of AMI decreased with increasing intake of alpha-carotene (odds ratios, OR = 0.71, 95% confidence intervals, CI 0.51-0.98, for the highest vs the lowest quartile of intake), beta-carotene (OR = 0.71, 95% CI 0.50-1.01) and beta-criptoxanthin (OR = 0.64, 95% CI 0.46-0.88). No associations emerged for total carotenoids, lycopene, lutein plus zeaxanthin and retinol. CONCLUSIONS: Our study suggests a weak protective effect of alpha-carotene, beta-carotene and beta-criptoxanthin on the risk of AMI. It also indicates that total carotenoids, lycopene, lutein plus zeaxanthin and retinol were not related to the risk of the disease.     

Pregnancy-related myocardial infarction

Introduction

The risk of acute myocardial infarction in young women is low, but increases during pregnancy due to the physiological changes in pregnancy, including hypercoagulability. Ischaemic heart disease during pregnancy is not only associated with increased maternal morbidity and mortality, but also with high neonatal complications. Advancing maternal age and other risk factors for cardiovascular diseases may further increase the risk of ischaemic heart disease in young women.

Methods

We searched the coronary angiography database of a Dutch teaching hospital to identify women with acute myocardial infarction who presented during pregnancy or postpartum between 2011 and 2013.

Results

We found two cases. Both women were in their early thirties and both suffered from myocardial infarction in the postpartum period. Acute myocardial infarction was due to coronary stenotic occlusion in one patient and due to coronary artery dissection in the other patient. Coronary artery dissection is a relatively frequent cause of myocardial infarction during pregnancy. Both women were treated by percutaneous coronary intervention and survived.

Conclusion

Physicians should be aware of the increased risk of myocardial infarction when encountering pregnant or postpartum women presenting with chest pain.