Kent L. Woods

A Meta-analysis of the Association of the Deletion Allele of the Angiotensin-Converting Enzyme Gene With Myocardial Infarction

BACKGROUND The ACE gene is characterized by a polymorphism based on the presence (insertion [I]) or absence (deletion [D]) within intron 16 of a 287-basepair alu repeat sequence, resulting in three genotypes (DD and II homozygotes and ID heterozygotes). In 1992, the DD genotype was reported to be associated with an increased risk of myocardial infarction (MI). Subsequent studies have produced conflicting findings. To further evaluate the association of the ACE I/D genotype with MI risk, we carried out a meta-analysis of all the published studies. METHODS AND RESULTS In total, 15 studies containing 3394 MI cases and 5479 control subjects were analyzed. The overall distribution of genotypes in the control subjects was 22.7% II, 49.0% ID, and 28.3% DD. The mean odds ratio for MI for DD versus ID/II genotypes across all studies was 1.26 (95% CI, 1.15, 1.39; P < .0001). Pairwise odds ratios were 1.36 (95% CI, 1.19, 1.55) for DD and II, 1.24 (95% CI, 1.11, 1.38) for DD and ID, and 1.09 (95% CI, 0.96, 1.23) for ID and II. The relative risk appeared to be increased in Japanese populations (2.55; 95% CI, 1.75, 3.70). CONCLUSIONS Within the limitations of the available data, the meta-analysis therefore supports an association of the ACE D allele with MI risk and strengthens the justification for further evaluation in appropriately powered studies.

QT dispersion and mortality after myocardial infarction

QT dispersion may serve as a measure of variability in ventricular recovery time and may be a means of identifying patients at risk of arrhythmias and sudden death after acute myocardial infarction. We investigated this possibility on electrocardiograms (ECGs) recorded 2 or 3 days after infarction (early) and at least 4 weeks later (late). 163 patients who died between 1 day and 5 years after infarct were compared with an equal number of survivors matched for age and sex. 53 of the patients who died and 82 survivors also had late ECGs. There was no difference in early QT dispersion between the patients who died and the survivors (mean QTc dispersion 112.1 [SD 44.4] vs 109.9 [42.7] ms1/2). QTc dispersion fell significantly from early to late ECGs in survivors (110.9 [48.5] to 76.5 [28.8] ms1/2), but not in patients who died during follow-up (108.0 [51.0] to 98.9 [43.1] ms1/2). The difference between the groups in the mean change was significant (34.4 [55.2] vs 9.1 [60.8] ms1/2, p = 0.016). QT dispersion measured on an ECG recorded 2 or 3 days after acute myocardial infarction does not predict mortality during the next 5 years. Increased QT dispersion on ECGs recorded at least 4 weeks after infarct may be associated with subsequent mortality, but this finding must be confirmed in a prospective trial.

Insertion/deletion polymorphism in the angiotensin-converting enzyme gene and risk of and prognosis after myocardial infarction.

OBJECTIVES We sought to prospectively investigate whether genetic variation at the angiotensin-converting enzyme gene locus defined by an insertion (I)/deletion (D) polymorphism influences the risk of myocardial infarction or prognosis after infarction, or both. BACKGROUND It has been suggested that the deletion allele of the angiotensin-converting enzyme gene, and specifically the DD genotype, may increase the risk of myocardial infarction, although previous studies have produced conflicting reports. No studies have yet examined the effect of I/D polymorphism on survival after infarction. METHODS Angiotensin-converting enzyme genotypes in 684 patients with myocardial infarction recruited at the time of the acute event through coronary care units in two centers were compared with those of 537 control subjects recruited from the base populations. All patients were followed up to assess the impact of the angiotensin-converting enzyme genotype on prognosis. RESULTS We found no difference (p = 0.89) in the genotype distribution between patients and control subjects (patients DD 31%, ID 47%, II 22%; control subjects DD 30%, ID 48%, II 22%). The odds ratio for myocardial infarction for DD compared with II/ID genotype adjusted for age, gender and center was 1.16 (95% confidence interval [CI] 0.82 to 1.65, p = 0.44). The study had 90% power to detect a 1.5-fold increase in risk of myocardial infarction associated with the DD genotype. For one center, data were available for other risk factors (hypertension, diabetes, angina, previous myocardial infarction, smoking, body mass index, total and high density lipoprotein cholesterol) in both patients and control subjects. In a stepwise logistic regression analysis the odds ratio for DD versus ID/II genotypes remained nonsignificant (1.44, 95% CI 0.84 to 2.46, p = 0.20) for these subjects. Over a median follow-up period of 15 months (range 3 to 22), 155 patients (22.7%) died. There was no difference in mortality between subjects with the DD genotype and those with ID/II genotypes. (21.8% vs. 23.1%, p = 0.25). Likewise, there was no difference in the distribution of survival times in the two groups (p = 0.62). The study had 70% power to detect a 1.5-fold increase in mortality during follow-up associated with the DD genotype. CONCLUSIONS We conclude that in the groups studied, genetic variation at the angiotensin-converting enzyme gene locus defined by I/D polymorphism does not significantly influence either the risk of or the short- to medium-term prognosis after myocardial infarction.

First myocardial infarction in patients of Indian subcontinent and European origin: comparison of risk factors, management, and long term outcome

Abstract Objectives: To compare long term outcome after first myocardial infarction among British patients originating from the Indian subcontinent and from Europe. Design: Matched pairs study. Setting: Coronary care unit in central Leicester. Subjects: 238 pairs of patients admitted during 1987-93 matched for age (within 2 years), sex, date of admission (within 3 months), type of infarction (Q/non-Q), and site of infarction. Main outcome measures: Incidence of angina, reinfarction, or death during follow up of 1-7 years. Results: Patients of Indian subcontinent origin had a higher prevalence of diabetes (35%v 9% in patients of European origin, P<0.001), lower prevalence of smoking (39% v 63%, P<0.001), longer median delay from symptom onset to admission (5 hours v 3 hours, P<0.01), and lower use of thrombolysis (50% v 66%, P<0.001). During long term follow up (median 39 months), mortality was higher in patients of Indian subcontinent origin (unadjusted hazard ratio=2.1, 95% confidence interval 1.3 to 3.4, P=0.002). After adjustment for smoking, history of diabetes, and thrombolysis the estimated hazard ratio fell slightly to 2.0 (1.1 to 3.6, P=0.02). Patients of Indian subcontinent origin had almost twice the incidence of angina (54% v 29%; P<0.001) and almost three times the risk of reinfarction during follow up (34% v 12.5% at 3 years, P<0.001). The unadjusted hazard ratio for reinfarction in patients of Indian subcontinent origin was 2.8 (1.8 to 4.4, P<0.001). Adjustment for smoking, history of diabetes, and thrombolysis made little difference to the hazard ratio. Coronary angiography was performed with similar frequency in the two groups; triple vessel disease was the commonest finding in patients of Indian subcontinent origin and single vessel disease the commonest in Europeans (P<0.001). Conclusions: Patients of Indian subcontinent origin are at substantially higher risk of mortality and of further coronary events than Europeans after first myocardial infarction. This is probably due to their higher prevalence of diffuse coronary atheroma. Their need for investigation with a view to coronary revascularisation is therefore greater. History of diabetes is an inadequate surrogate for ethnic origin as a prognostic indicator. Key messages The cumulative incidence of reinfarction after a first myocardial infarct is threefold higher in patients of Indian subcontinent origin than in European patients Patients of Indian subcontinent origin have poorer survival after first myocardial infarction The commonest coronary angiographic finding in patients of Indian subcontinent origin is triple vessel disease A history of known diabetes is not in itself an adequate marker of adverse prognosis in this ethnic group After myocardial infarction, patients of Indian subcontinent origin have a high risk of recurrent myocardial ischaemia and an increased likelihood of needing coronary revascularisation

Modification of the circadian rhythm of onset of acute myocardial infarction by long-term antianginal treatment

Objective—To elucidate the mechanism of the circadian pattern of onset of acute myocardial infarction by examining the effects of prior antianginal treatment upon it. Design—Retrospective analysis of clock time of the onset of acute myocardial infarction by linear modelling to define the circadian distribution of hourly onset rates and to examine the deviation of treated groups of patients from this distribution. Setting—Coronary care unit in a general hospital taking unselected acute admissions from a district of 0·9 million people. Patients—A series of 2231 patients with confirmed acute myocardial infarction. Results—A major 24 h cycle and smaller 12 h and 6 h cycles were present in patients not taking antianginal medication. Onset rates varied twofold over the day, with maxima around 10.00 am and 10.00 pm. This pattern was unchanged in patients on prior treatment with regular nitrates, but in those who had been taking a β blocker or a calcium antagonist the 24 h cycle was absent. Conclusions—These results are best explained by the shared property of β blockers and calcium antagonists to reduce blood pressure and myocardial oxygen demand. The mid-morning peak of the onset of myocardial infarction is attributable to the physiological increase in sympathetic drive and cardiac work at that time. The data are not consistent with the triggering of the 24 h periodicity by fluctuations in coronary tone or haemostatic activity.

Three-lead measurement of QTc dispersion.

QTc Dispersion. Introduction: QTc dispersion has traditionally been calculated from all 12 leads of a standard electrocardiogram (ECG). It is possible that alternative, quicker methods using fewer than 12 leads could be used to provide the same information.

Prognostic value of admission blood glucose concentration and diabetes diagnosis on survival after acute myocardial infarction: results from 4702 index cases in routine practice

The diagnosis of diabetes and admission blood glucose concentration are associated with adverse outcome after acute coronary syndromes. We compared the relative association with survival after ST elevation AMI (acute myocardial infarction) of admission blood glucose concentration and of diabetes diagnosis. We carried out a retrospective cohort study in 4702 consecutive patients with STEMI (ST elevation AMI) occurring from 1 April 1993 to 31 December 2005, assessed for mortality at 30 days and 1 year. Patients were classified according to antecedent diabetes and by blood glucose concentration at admission (quartile 1, <7 mmol/l; quartile 2, 7–8.2 mmol/l;quartile 3, 8.3–10.9 mmol/l; quartile 4, 11 mmol/l). Multivariable models were constructed for determinants of mortality, including year of STEMI and demographic variables, entering blood glucose concentration and antecedent diabetes individually and together. All-cause 30-day and 1-year mortality were 22.8% and 31.3% for patients with antecedent diabetes, compared with 16.3% and 23.0% respectively for those without. For glucose quartiles 1, 2, 3 and 4, crude 30-day mortality was 9.0%, 10.6%, 17.9% and 31.0%. Adjusted 30-day mortality risk was similar in quartile 2, higher by >80% in quartile 3 and by >150% in quartile 4, compared with glucose quartile 1. Antecedent diabetes was associated with an increase in mortality [unadjusted odds ratio (OR)1.52 (95% CI 1.24, 1.86)]. On multivariable analysis (excluding glucose quartile), this reduced to 1.24 (0.98, 1.58) and changed to a small, statistically non-significant reduction in risk when glucose quartile was added to the analysis [adjusted OR 0.87 (0.67, 1.13)]. Inclusion of antecedent diabetes in multivariable models did not add to the predictive value for mortality of glucose quartile(P=0.368). Similar relationships were observed for 1 year mortality. In patients with STEMI, blood glucose concentration shows graded association with risk of 30-day and 1-year mortality and is of greater prognostic relevance than antecedent diabetes diagnosis. Moderate elevation of blood glucose, below levels previously considered to be clinically relevant, is associated with adverse impact on survival.

Intravenous magnesium in suspected acute myocardial infarction.

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Utilisation of Thrombolytic Therapy in Older Patients with Myocardial Infarction

Empirical evidence from many countries, obtained from sampling populations of patients admitted to hospital with acute myocardial infarction, has confirmed that elderly patients are significantly less likely to receive thrombolytic therapy. This difference persists after controlling for confounding factors such as admission delay and contraindications to thrombolysis. However, evidence supporting the efficacy of thrombolysis in reducing mortality after acute myocardial infarction is less clear cut in patients aged 75 years or above than in younger patients. These older patients are substantially under-represented in the clinical trials although they constitute one third of the clinical population. Observational studies indicate that older patients are at slightly higher risk than younger patients of experiencing haemorrhagic stroke after thrombolysis. It is, however, unlikely that efficacy and tolerability considerations alone account for the low use of thrombolytics in the elderly as similar trends are seen for other modalities of treatment of acute myocardial infarction. Since older patients have the highest mortality risk after myocardial infarction, they have the greatest potential gain from thrombolytic treatment, assuming a uniform treatment effect across age. The estimated cost effectiveness (cost per quality-adjusted life-year gained) improves with increasing age. It is concluded that patient age should not influence the treatment decision concerning thrombolysis. To ensure that elderly patients receive maximum benefit from this therapeutic advance requires attention to referral patterns from the community, speed of assessment in hospital and a clear treatment policy without age constraints. The effectiveness of these measures should be routinely audited.

Magnesium in acute myocardial infarction.

EDITOR,—Salim Yusuf and Marcus Flather1 offer no satisfactory explanation for the statistical incompatibility (P>0.0001 for heterogeneity) between the inefficacy of magnesium in the fourth international study of infarct survival (ISIS-4)2 and the clearly positive pooled results of the 10 other trials of intravenous magnesium in acute myocardial infarction. Magnesium has been reported to protect contractile function in a dozen experimental models of myocardial ischaemia and reperfusion and is now known to act during the first few minutes of reperfusion.3 4 ISIS-4 was unique in that most …