Interaction between gene polymorphisms of renin-angiotensin system and metabolic risk factors in premature myocardial infarction

The renin-angiotensin system is involved in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). The authors investigated the association of genetic variability in the renin-angiotensin system (RAS) with premature MI and interactive effects between gene polymorphisms and metabolic risk factors on MI risk. Their study compared 142 patients with MI younger than 55 years with 142 healthy subjects. Polymorphisms of angiotensin-I converting enzyme (ACE) gene (insertion/deletion), angiotensinogen gene (M235T), and angiotensin-II type-1 receptor (AGT1R) gene (A1166C) were tested. The ACE-DD (deletion/deletion) genotype conferred a twofold independent risk for MI (confidence interval [CI] = 1.1-3.7; p = 0.01) after adjustment for cardiovascular risk factors, whereas angiotensinogen-TT genotype and AGT1R-AA genotype were not independent risk factors for MI. An interactive effect on MI risk was found between ACE-DD and AGT1R-AA genotypes (odds ratio [OR]=2, 95% CI= 1-3.9), between ACE-DD and angiotensinogen-TT genotypes (OR = 2.7, 95% CI = 1-7.3), as well as among ACE-DD, angiotensinogen-TT, and AGT1R-AA genotypes (OR=4.8, 95% CI = 1-22.8). Similarly, metabolic risk factors interacted with angiotensinogen-TT genotype (OR= 2, 95% CI = 1.1-3.9) on MI risk. The ACE-DD genotype is an independent risk factor for MI in patients younger than 55 years. Additionally, the authors provide evidence of an interactive effect on MI risk between risk genotypes of RAS, as well as between the angiotensinogen-TT genotype and metabolic risk factors.     

Genetic polymorphisms of the renin-angiotensin system and atheromatous renal artery stenosis

Genes that influence the renin-angiotensin system have been investigated in recent years as potential etiologic candidates of cardiovascular and renal diseases. In atheromatous renal artery stenosis (RAS), a condition characterized by persistent activation of the renin-angiotensin system, the study of these genes may be of particular relevance. We evaluated angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T, and angiotensin II receptor (ATR) A1166C polymorphisms in relation to the occurrence of RAS. We studied 58 patients with angiographically documented RAS; 102 normotensive subjects with normal coronary arteries and no history or clinical or instrumental evidence of atherosclerosis in other vascular districts were considered the control group. Patients had a significantly higher D allele frequency (0.70 versus 0.55; chi(2) 6.88, P=0.01; odds ratio [OR] 1. 9, 95% CI 1.17 to 3.07) than did the control population; 48.3% of patients were homozygous for DD (chi(2) 6.62, P<0.05; OR 2.04, 95% CI 1.05 to 3.95); and only 8.6% carried the II genotype (OR 0.34, 95% CI 0.19 to 1.47). No significant association was found for AGT M235T and ATR A1166C. Our results suggest a predisposing role for ACE genetic polymorphism in the development and progression of atheromatous RAS.     

Angiotensinogen T174M and M235T gene polymorphisms are associated with the extent of coronary atherosclerosis.

BACKGROUND: The relations of the angiotensinogen (AGT) T174M and M235T gene polymorphisms to the risk of coronary heart disease (CHD) have been investigated in only a few studies with conflicting results. RESULTS: Therefore, we analysed the relationship of the AGT gene polymorphisms to the presence and extent of CHD in 2250 male Caucasians whose coronary anatomy was defined by means of coronary angiography. The relative frequencies of the T and M alleles of the T174M and of the M235T gene variation did not significantly differ between patients without or with single-, double- or triple-vessel disease and between subjects without or with myocardial infarction (MI). In contrast the mean CHD score--defined by Gensini--was higher within MM homozygotes of the T174M gene variation than within TT genotypes; TM subjects had intermediate values. In M235T genotypes, mean CHD scores were similar in the total sample and in older individuals (> or = 62 years), whereas in younger individuals (< 62 years) a higher CHD score was found within AGT 235 T allele carriers than within MM homozygotes. In younger individuals with high apoAI plasma levels, the mean CHD score was clearly higher within TT homozygotes of the M235T gene variation than within MM genotypes; MT subjects had intermediate values. An interaction between both angiotensinogen gene polymorphisms on the extent of CHD or on the risk of non-fatal MI were not observed when the M allele of AGT T174M was combined either with the T allele or the TT genotype of M235T. CONCLUSIONS: The present study strengthens the hypothesis of an association of both angiotensinogen gene polymorphisms with the extent of coronary heart disease.     

Genotypic interactions of renin-angiotensin system genes in myocardial infarction

BACKGROUND: Three-gene interactions among the genetic polymorphisms of the renin-angiotensin system (RAS) associated with acute myocardial infarction (AMI) have not been examined in a single population. We hypothesized that all types of gene-to-gene associations may occur in AMI, but that some will have a higher risk, depending on the gene frequencies. METHODS: Polymorphisms of the AGT (M235T), ACE (I/D) and AGTR1 (A1166C) genes in AMI patients and controls were analyzed using the polymerase chain reaction. Classic coronary risk factors were analyzed in all individuals. RESULTS: Logistic regression analysis of these factors and the genetic polymorphisms demonstrated that smoking, family history of CAD, arterial hypertension and total cholesterol were the most significant contributors to AMI. The genotypic frequencies for all three genes alone were similar between the infarction and control groups, with no increased risk of developing AMI. Double homozygous combinations for normal alleles (MM of AGT, II of ACE and AA of AGTR1) had a lower risk of AMI (odds ratio<0.38), indicating a protective effect in these individuals. In genotypic combinations that included at least one unfavorable allele, the risk (odds ratio) of developing AMI was 2.92, 2.63 and 2.68 for AGT vs. ACE, AGT vs. ATR1 and ACE vs. AGTR1, respectively. The positive interaction among the three genes and the risk of AMI had an odds ratio of 3.78 with a 95% CI of 0.88-12.85. CONCLUSIONS: The risk of developing AMI is higher whenever there are unfavorable alleles in gene-to-gene associations in the RAS.     

G-protein beta3 subunit (GNB3) gene polymorphisms and cardiovascular disease: the Ludwigshafen Risk and Cardiovascular Health (LURIC) study

A common 825C>T polymorphism in exon 10 of the gene for the beta-3 subunit of heterotrimeric G-proteins, GNB3, has been associated in some studies with traits of the metabolic syndrome as well as coronary artery disease (CAD), but these associations were refuted by other studies. To investigate the role of GNB3 gene variations in CAD and myocardial infarction (MI), we determined five GNB3 polymorphisms (-1429G>A, IVS5 +41G>A, 657T>A, 814G>A and 825C>T) in the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort, including 2575 patients with angiographically documented CAD and 731 individuals in whom CAD had been ruled out by angiography. None of the GNB3 polymorphisms was associated with CAD, MI, diabetes, hypertension, blood pressure, body weight or body mass index. We conclude that a major contribution of GNB3 gene variants to CAD or MI risk is unlikely.     

Renin-angiotensin system gene polymorphisms and coronary artery disease in a large angiographic cohort: detection of high order gene-gene interaction

There have been many reports regarding the association between renin-angiotensin system (RAS) gene polymorphisms and coronary artery disease (CAD) or acute myocardial infarction (AMI), but the results are inconsistent. In the present study, we used several new approaches with multilocus data to reappraise this issue in a large and relatively homogeneous Taiwanese population. A total of 1254 consecutive patients who underwent cardiac catheterization (735 with documented coronary artery disease and 519 without) between 1996 and 2003 were recruited. Angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen gene; and A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In single-locus analyses, no locus was associated with CAD, history of AMI and three-vessel CAD, either with or without adjustment for conventional CAD risk factors. For multilocus analyses, we recreated a balanced population, with the controls individually matched to the cases regarding the conventional CAD risk factors. We found that the angiotensinogen gene haplotype profile was significantly different between the cases and controls (chi2=31.6, P=0.030) in haplotype analyses. Furthermore, significant three-locus (G-217A, M235T and I/D) gene-gene interactions were detected by multifactor-dimensionality reduction method (highest cross-validation consistency 10.0, lowest prediction error 40.56%, P=0.017) and many even higher order gene-gene interactions by multilocus genotype disequilibrium tests (16 genotype disequilibria exclusively found in the controls, all of which included at least two genes among AGT, ACE and AT1R genes). Our study is the first to demonstrate epistatic, high-order, gene-gene interactions between RAS gene polymorphisms and CAD. These results are compatible with the concept of multilocus and multi-gene effects in complex diseases that would be missed with conventional approaches.     

CD14 gene -159C/T polymorphism is not associated with coronary artery disease and myocardial infarction

Background Monocyte differentiation antigen CD14 is considered an important cell-activating mediator of inflammatory responses that may result in atherosclerosis, coronary artery disease (CAD), thrombus formation, and myocardial infarction (MI). We assessed the possibility that a C → T nucleotide substitution polymorphism in the promoter (position −159) of the gene encoding CD14 constitutes a risk factor for CAD and MI. Methods Consecutive patients with significant, angiographically documented coronary stenoses but without symptoms or signs of old or acute MI constituted the group with CAD (n = 998). Consecutive patients with angiographic examination with old or acute MI constituted the group with MI (n = 793). Subjects matched with patients for age and gender but without angiographic evidence of CAD and without symptoms or signs of MI (n = 340) and a group of healthy blood donors (n = 104) served as controls. Results Genotype distributions of the −159C/T polymorphism were similar across the groups; CC:CT:TT was 26.9%:51.0%:22.1% in blood donors, 25.9%:52.0%:22.1% in matched control subjects, 27.4%:49.9%:22.7% in patients with CAD, and 29.2%:49.2%:21.6% in patients with MI. The lack of association persisted also after adjustment for the presence of conventional cardiovascular risk factors. In addition, no significant differences were found between genotype distributions of control subjects and selected subgroups of patients with CAD or MI. Conclusion These findings indicate that, in the sample of patients examined in this study, the −159C/T polymorphism of the CD14 gene is not related to CAD or MI. (Am Heart J 2002;143:971-6.)     

Long-term outcomes of optimized medical management of outpatients with stable coronary artery disease

The objective of this study was to assess long-term clinical outcomes and their correlates in medically managed outpatients with stable angina pectoris, healed myocardial infarction (MI), or documented asymptomatic coronary artery disease (CAD). Management strategy emphasized maximally tolerated medical therapy and modification of coronary risk factors. Referral to invasive coronary interventions followed stricter criteria than standard published guidelines. Primary study outcomes were all-cause mortality or nonfatal myocardial infarction. Secondary study outcomes included cardiac death, unstable angina, or coronary revascularization. A total of 693 men and women with proved CAD (mean age 67 years at entry, 85% men, 41% with history of MI) were enrolled. The annual incidence of nonfatal MI, cardiac mortality, and total mortality was 2.2%, 0.8%, and 1.4%, respectively, during an average follow-up of 4.6 years. Coronary revascularization was performed in 24% of subjects; unstable or progressive anginal symptoms were the most common reasons for revascularization. In patients with documented stable CAD, a management strategy based on intensive medical therapy and modification of established coronary risk factors was associated with excellent long-term outcomes. Thus, coronary interventions can be safely delayed until clinical instability ensues, without increased risk of MI or death. This treatment approach represents a viable alternative to invasive strategies.     

The 3'-UTR C>T polymorphism of the oxidized LDL-receptor 1 (OLR1) gene does not associate with coronary artery disease in Italian CAD patients or with the severity of coronary disease

BACKGROUND AND AIM: Oxidized low-density lipoproteins (OxLDLs) play a critical role in endothelial dysfunction, which is implicated in the pathogenesis of atherosclerosis. Vascular endothelial cells internalize and degrade oxLDL through the endothelial lectin-like oxidized LDL receptor 1 (OLR1). OLR1 is up-regulated in several pathological conditions, including hypertension, hyperlipidemia, diabetes, atherosclerosis and inflammation, and represents therefore a good candidate for coronary artery disease (CAD). Recently, a 3'-UTR (188 C>T) SNP in the OLR1 gene has been reported to be associated with coronary artery stenosis and myocardial infarction. In the present study we investigated whether the OLR1 gene 188 C>T SNP is a genetic risk marker for CAD in Italian patients with angiographically defined coronary atherosclerosis, and assessed its relation with clinical and metabolic abnormalities, including severity of disease (classified as restenosis, single- or multiple coronary vessels disease, and MI). METHODS: The 3'-UTR C>T SNP was detected in real-time PCR in 351 subjects with CAD and in 215 control subjects. RESULTS: The OLR1-T allele frequencies were 48.9% in the CAD subjects and 47.7% in controls, with no significant difference between the two groups. Also, the 3'-UTR C>T SNP did not associate with any of the parameters of severity of disease. Furthermore, none of the other clinical and metabolic parameters were associated with the OLR1 gene SNP. CONCLUSIONS: Our observations suggest that, in our population, the 3'-UTR C>T polymorphism of the OLR1 gene is unlikely to play a role in the pathogenesis of coronary artery disease.     

Obstructive sleep apnea as a risk marker in coronary artery disease

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with a range of cardiovascular sequelae and increased cardiovascular mortality. The aim of our study was to assess the prevalence of OSA in patients with symptomatic angina and angiographically verified coronary artery disease (CAD). In addition, we analyzed the association of OSA and other coronary risk factors with CAD and myocardial infarction. METHODS: Overnight non-laboratory-monitoring-system recordings for detection of OSA was performed in 223 male patients with angiographically verified CAD and in 66 male patients with exclusion of CAD. A logistic regression analysis was performed to assess associations between risk factors and CAD and myocardial infarction. RESULTS: CAD patients were found to have OSA in 30.5%, whereas OSA was found in control subjects in 19.7%. The mean apnea/hypopnea index (AHI) was significantly higher (p < 0.01) in CAD patients (9.9 +/- 11.8) than in control subjects (6.7 +/- 7.3). Body-mass-index (BMI) was significantly higher in patients with CAD and OSA than in patients with CAD without OSA (28. 1 vs. 26.7 kg/m(2); p < 0.001). No significant difference was found with regard to other risk factors and left ventricular ejection fraction (LVEF) between both groups. Hyperlipidemia (OR 2.3; CI 1. 3-3.9; p < 0.005) and OSA defined as AHI >/=20 (OR 2.0; CI 1.0-3.8, p < 0.05) were independently associated with myocardial infarction. CONCLUSIONS: There is a high prevalence of OSA among patients with angiographically proven CAD. OSA of moderate severity (AHI >/=20) is independently associated with myocardial infarction. Thus, in the care of patients with CAD, particular vigilance for OSA is important.     

Association study of CD14 polymorphism with myocardial infarction in a Japanese population

There have been many studies investigating the association between gene polymorphisms and coronary artery disease (CAD) including myocardial infarction (MI), and some studies have shown that certain gene polymorphisms are associated with CAD/MI. However, the results of the association have sometimes been controversial. The reason may be that the contribution of genetic risk factors to CAD/MI varies depending on the ethnic, environmental, and habitual backgrounds, and differs between males and females. In this study, we analyzed 17 polymorphisms in 12 candidate genes for MI in 136 patients and 200 to 235 controls, and found that there is a significant association of MI with the polymorphisms in the genes for E-selectin and CD14 receptor. To further explore the association, we investigated the C-260 T polymorphism in the promoter region of the CD14 gene in 502 MI patients and 527 control subjects. The genotype distributions of the CD14 polymorphism were as follows: patients; T/T 32.5%, C/T 48.2%, C/C 19.3%, and controls; T/T 25.4%, C/T 52.8%, C/C 21.8%. The frequencies of the T/T homozygotes were significantly higher in the patients (OR = 1.41, P = 0.013) than in the control group, confirming the association of CD14 polymorphism with MI in Japanese. Stratification analyses further demonstrated that the association was more prominent in females and in patients with a relatively low body mass index, suggesting that the contribution of the CD14-linked genetic risk to MI differs with respect to gender and habitual background.     

Angiotensin I-converting enzyme gene polymorphism in a low-risk European population for coronary artery disease

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) has been associated with an increased risk of coronary artery disease (CAD) and myocardial infarction (MI). However, this finding has not been fully investigated in European populations with very low CAD risk. In a case-control study on a population from Southern Europe (Toulouse, France), we evaluated the ACE I/D polymorphism in 405 men, aged 35–65 years, who underwent coronary angiography and in 357 representative control men within the same age range. We also explored associations in the patients between this polymorphism and CAD severity. The ACE genotype was not associated with the presence of either CAD or MI. The ACE genotype was not a marker for angiographically assessed CAD severity. In a sample in one of the European populations with the lowest CAD risk, ACE I/D polymorphism was not associated with an increased risk for CAD or MI and did not influence the extent of CAD.     

Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction

BACKGROUND: Elevated plasma homocysteine level is an independent risk factor for cardiovascular disease. A common mutation (nucleotid 677C-T) in the gene coding for methylenetetrahydrofolate reductase (MTHFR) has been reported to reduce the enzymatic activity of MTHFR and is associated with elevated plasma levels of homocysteine, especially in subjects with low folate intake. HYPOTHESIS: Methylenetetrahydrofolate reductase T/T genotype may be a risk factor for premature MI in Turkish population who are known to have low folate levels. METHODS: The study group was comprised of 96 men (aged <45 years) with premature myocardial infarction (MI) and 100 age- and gender-matched controls who had no history or clinical evidence of coronary artery disease (CAD) and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with HinfI, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented. RESULTS: Allele and genotype frequencies among cases and control subjects were compatible with Hardy-Weinberg equilibrium. The frequencies of T/T, C/T, and C/C genotypes among patients with MI and control subjects were 15.6, 40.6, and 43.8%, and 5, 35, and 60%, respectively. Multivariate analyses identified smoking, MTHFR C/T polymorphism, diabetes mellitus, family history of CAD, and hypertension as the independent predictors of premature MI. Defining patients with non-T/T genotype (C/C and C/T combined) as reference, the relative risk of MI for subjects with T/T genotype was 5.94 (95% confidence interval: 1.96-18.02, p = 0.0016). CONCLUSIONS: Our findings suggest that C677T transition in the MTHFR gene may be a risk factor for premature MI in Turkish men.     

Different impact of deletion polymorphism of gene on the risk of renal and coronary artery disease.

OBJECTIVE: An increased frequency of the angiotensin converting enzyme (ACE) D variant has recently been reported in patients with atheromatous renal artery disease (RAD), whereas controversy exists on the risk of coronary artery disease (CAD) associated with this polymorphism. In spite of the frequent coexistence of RAD and CAD, no studies have specifically compared ACE insertion/deletion (I/D) polymorphism in patients with coronary versus renal artery disease or defined the risk of each disease associated with the D variant. DESIGN: We designed a large case-control study of subjects for whom objective renal or coronary angiographic documentation was available. METHODS AND RESULTS: We analysed ACE I/D genotype and clinical-biochemical data of a total of 942 subjects (123 patients with and 137 without angiographic evidence of RAD, 420 patients with and 262 without angiographic evidence of CAD). Renal (with and without RAD) and coronary patients were similar for most conventional risk factors. There was no difference in DD frequency between CAD and CAD-free patients (38.1 versus 33.6%, NS) and DD homozygosity was not associated with CAD risk (OR = 1.27, 95% CI = 0.82-1.98). In contrast, the DD genotype was more frequent in RAD than in RAD-free patients (54.5 versus 39.4, P < 0.05) and was associated with a 2.25-fold increased risk of RAD in both the univariate and multivariate logistic regression models. Additional predictors of RAD were age and creatinine. In RAD/RAD-free patients with angiographically documented CAD, DD homozygosity was confirmed to be preferentially associated with RAD (P < 0.05). CONCLUSIONS: ACE D variant is preferentially associated with atherosclerotic renal rather than with coronary disease, despite similar exposure to atherogenic noxae. DD homozygosity confers a 2.25-fold increased risk of RAD.     

The evolving pattern of symptomatic coronary artery disease in the United States and Canada: baseline characteristics of the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial

Major improvements in medical therapy and percutaneous coronary intervention for coronary artery disease (CAD) have emerged during the previous 2 decades, but no randomized trial in patients with stable CAD has been powered to compare these 2 strategies for the hard clinical end points of death or myocardial infarction (MI), and previous studies have not evaluated the effect of coronary stents and intensive medical therapy on cardiac events during long-term follow-up. Between 1999 and 2004, 2,287 patients with documented myocardial ischemia and angiographically confirmed CAD were randomized to the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial, with a principal hypothesis that a strategy of percutaneous coronary intervention plus intensive, guideline-driven medical therapy would be superior to a strategy of intensive medical therapy alone. The primary end point was a composite of all-cause mortality or acute MI (time to first event) during a 2.5- to 7-year (median 5) follow-up. Baseline characteristics were a mean age of 62 +/- 5 years, 85% men, and 86% Caucasian. Mean duration of angina before randomization was 26 months (average 10 episodes/week), and 29% of patients were smokers, 67% had hypertension, 38% had previous MI, 71% had dyslipidemia, 34% had diabetes, 27% had previous revascularization, and 69% had multivessel CAD. Approximately 55% of patients met established criteria for the metabolic syndrome. In conclusion, baseline characteristics of the COURAGE trial study population indicate a highly symptomatic group of patients with CAD who have a significant duration and frequency of antecedent angina pectoris and a high prevalence of cardiac risk factors.     

T(-786)--> C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with myocardial infarction, especially without coronary organic stenosis

Recently, we discovered a T(-786)-->C mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene that is associated with coronary spasm. The precise mechanism(s) of myocardial infarction (MI), especially without coronary organic stenosis, has not been elucidated, but it seems possible that coronary spasm plays a key role in the mechanism. In this study, we examined the frequency with which the T(-786)-->C mutation occurred in 359 patients with MI who were compared with 195 controls. In the MI group, the frequency of C/C, C/T, and T/T genotypes was 1%, 22%, and 77%, respectively. In the control group, the frequency of C/C, C/T, and T/T genotypes were 0%, 8%, and 92%, respectively. The frequency of the C allele was significantly higher in the MI group than in the control group (p < 0.001). In the MI group, 30 of 359 patients (8%) with MI had no stenosed vessels angiographically, 158 (44%) had 1 stenosed vessel, 80 (22%) had 2 stenosed vessels, and 91 (25%) exhibited 3 stenosed vessels. Total and low-density lipoprotein cholesterol levels and the incidence of diabetes mellitus increased as the number of stenosed vessels increased (p < 0.01, respectively). The frequency of the T(-786)-->C mutation was significantly higher in MI patients with no stenosed vessels (50%) than in those with stenosed vessels (p < 0.003). In conclusion, the T(-786)-->C mutation was strongly associated with MI, especially without coronary arterial stenosis, in Japanese patients. The association may be due to the impaired effects of nitric oxide in the cardiovascular system.     

Electrocardiographic, arteriographic and ventriculographic correlations in transmural myocardial infarction

To determine if significant interrelations exist between the electrocardiographic diagnosis of transmural myocardial infarction, sites of coronary arterial obstruction, and left ventricular asynergy, 235 patients with angiographically documented coronary artery disease were subdivided according to the electrocardiographic location of the myocardial infarction, the coronary arterial system involved and the site of ventricular asynergy. Of 82 instances of anterior myocardial infarction, the left anterior descending artery demonstrated significant disease in 79 (96 percent). Of 100 instances of inferior myocardial infarction, the right coronary artery was significantly diseased in 87 and the left circumflex in 55. When multiple infarctions were present, multivessel disease was found in 93 percent of patients. Left ventricular asynergy was present in 81 percent, including 84 percent of those with anterior infarction, 74 percent of those with inferior infarction, and 93 percent of those with multiple infarctions. The results of our study suggest that the electrocardiogram is often of value in indicating sites of coronary arterial obstruction and ventricular asynergy in patients with coronary artery disease and transmural myocardial infarction.     

Presentation and late outcome of myocardial infarction in the absence of angiographically significant coronary artery disease

To determine the natural history of myocardial infarction (MI) in the absence of angiographically significant (no lesion greater than or equal to 50% diameter stenosis) fixed coronary artery disease (CAD), clinical and angiographic data and late outcome were studied in 43 such patients. The mean age was 45 +/- 11 years; 32 patients (74%) were cigarette smokers. Mild fixed CAD, present in 38 patients (88%), was more frequent in the artery supplying the MI zone (p less than 0.01). Filling defects or serial angiographic resolution of obstruction in the artery supplying the MI zone were present in 14 patients (33%). At late follow-up, 14 major cardiac events occurred in 9 patients, including revascularization in 3, recurrent MI in 6 and cardiac death in 5. Of 35 patients undergoing catheterization within 1 year of the index MI, cumulative risk of a major cardiac event was 9 +/- 4, 12 +/- 5 and 20 +/- 7% at 3, 19 and 37 months, respectively. Myocardial infarction in the absence of significant fixed CAD tends to occur in young smokers with mild CAD in the artery serving the MI zone. Superimposed intracoronary thrombus can be frequently implicated. In these patients, subsequent major cardiac events may occur more frequently than previously reported.     

血电解质和白蛋白浓度与冠状动脉病变严重性的关系

目的:探讨血电解质钠、钾、钙及白蛋白浓度与冠状动脉病变严重程度的关系。方法:回顾性分析358例冠心病介入诊疗者资料,其中冠心病者(冠心病组)286例,含急性心肌梗死(AMI)者51例,陈旧性心肌梗死(OMI)者56例,无心肌梗死(MI)冠心病者179例;冠状动脉造影(CAG)示无粥样硬化改变者(对照组)72例。采用Gensini积分系统评定冠状动脉病变严重性。结果:冠心病组中,平均冠状动脉病变Gensini积分AMI亚组[39(27~72)]最高,OMI亚组[36(22~57)]次之,无MI冠心病亚组[28(15~42)]最低(P<0.01);冠心病组患者平均血钙[AMI:(2.13±0.29)mmol/L,OMI:(2.34±0.22)mmol/L,无MI冠心病:(2.36±0.22)mmol/L]和白蛋白[AMI:(38.5±5.1)g/L,OMI:(41.3±3.9)g/L,无MI冠心病:(41.6±3.6)g/L]均明显低于对照组[血钙:(2.42±0.15)mmol/L,白蛋白:(42.8±4.0)g/L],均P<0.05,其中AMI亚组平均血钙和白蛋白还均明显低于其他冠心病亚组(均P<0.05);...     

Detection of coronary artery disease with 13N-ammonia and high-resolution positron-emission computed tomography

In order to evaluate the detectability of coronary artery disease (CAD) with positron-emission computed tomography (PET), we performed 13N-ammonia myocardial PET scanning at rest and with exercise loading in 20 normal subjects and 40 patients with CAD, by means of a high-resolution, multi-slice, whole-body PET scanner. Myocardial PET scanning was performed 3 minutes after injection of 13N-ammonia at rest and during exercise. The circumferential profile analysis of resting PET images revealed regional hypoperfusion in 96% of CAD patients with previous myocardial infarction and in 29% of those without infarction. Exercise PET studies showed high sensitivity (93%) in detecting CAD without myocardial infarction, whereas no abnormal hypoperfusion was detected in normal subjects. Segmental analysis of regional myocardial perfusion with exercise stress identified 67 of 75 stenosed vessels (89%). We conclude that 13N-ammonia myocardial PET with exercise loading provides high-quality tomographic images of regional myocardial perfusion and is a valuable technique for detecting CAD.