Approaches to understanding and interpreting the risks of red blood cell transfusion in neonates.

In this review, we explore how to assess potential harm related to neonatal transfusion practice. We consider different sources of information, including passive or active surveillance systems such as registries, observational studies, randomised trials and systematic reviews. Future research directions are discussed.

Molecular analysis and genotype-phenotype correlation of Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) features hypoplastic anemia and congenital malformations, largely caused by mutations in various ribosomal proteins. The aim of this study was to characterize the spectrum of genetic lesions causing DBA and identify genotypes that correlate with phenotypes of clinical significance. Seventy-four patients with DBA from across Canada were included. Nucleotide-level mutations or large deletions were identified in 10 ribosomal genes in 45 cases. The RPS19 mutation group was associated with higher requirement for chronic treatment for anemia than other DBA groups. Patients with RPS19 mutations, however, were more likely to maintain long-term corticosteroid response without requirement for further chronic transfusions. Conversely, patients with RPL11 mutations were less likely to need chronic treatment. Birth defects, including cardiac, skeletal, hand, cleft lip or palate and genitourinary malformations, also varied among the various genetic groups. Patients with RPS19 mutations had the fewest number of defects, while patients with RPL5 had the greatest number of birth defects. This is the first study to show differences between DBA genetic groups with regards to treatment. Previously unreported differences in the rate and types of birth defects were also identified. These data allow better patient counseling, a more personalized monitoring plan, and may also suggest differential functions of DBA genes on ribosome and extra-ribosomal functions.

Detection of Epstein-Barr virus in leucoreduced blood products.

This study examined the prevalence of three human herpesviruses (HHV), namely HHV-4 (Epstein-Barr virus/EBV), HHV-6b and HHV-7 in leucoreduced blood products obtained from the Sainte-Justine Hospital blood bank. A total of 100 specimens, including 34 red blood cell concentrates, 33 platelet bags and 33 plasma units, were collected and screened by a sensitive PCR assay using virus-specific primers. Positive units were then retested by quantitative PCR. Of the 100 specimens, one platelet unit tested positive for EBV.

Incidence of hypotension and acute hypotensive transfusion reactions following platelet concentrate transfusions.

BACKGROUND AND OBJECTIVES: Platelet concentrates (PCs) are associated with transfusion reactions involving hypotension, particularly bradykinin-mediated acute hypotensive transfusion reactions. This study aims to determine the incidence of hypotensive events and more specifically acute hypotensive transfusion reaction associated with PC transfusions. We also sought to ascertain whether these reactions are associated with elevated bradykinin levels. MATERIALS AND METHODS: This is a prospective descriptive study of PCs administered at Sainte-Justine Hospital over 28 months. All PCs administered during this period were screened for hypotension through review of all transfusion-associated reaction reports (TARRs) sent to the blood bank. All residual PC bags were returned to the blood bank. TARRs associated with hypotension were reviewed by adjudicators that established the imputability of the PC transfusion to the reaction. Bradykinin levels were sampled in the first 168 PC bags returned to the blood bank. Levels were compared between PCs associated with hypotension and control PCs not associated with hypotension. RESULTS: A total of 3672 PC bags were returned to the blood bank; 25 PCs were associated with hypotension. Adjudicators ascertained that five hypotensive events were imputable to PCs of which one was an acute hypotensive transfusion reaction (incidence: 0·03%). Bradykinin level in the latter PC was 10 pg/ml, whereas levels were 226·2 ± 1252 pg/ml in the 143 control PCs. CONCLUSION: Our results show a low incidence of hypotension after PC transfusion. We identified only one acute hypotensive transfusion reaction. No correlation between bradykinin level and the occurrence of acute hypotensive reactions could be observed given that only one event was identified.

Association between plasma transfusions and clinical outcome in critically ill children: a prospective observational study.

BACKGROUND AND OBJECTIVES: Plasma transfusions are commonly used in adult and paediatric intensive care units. Recent data suggest an association between plasma transfusions and worse clinical outcome in adult trauma patients. To date, no prospective paediatric study has addressed this issue. Our objective was to prospectively analyse the association between plasma transfusions and clinical outcome of critically ill children. MATERIALS AND METHODS: Prospective, observational and single centre study that includes all consecutive admissions to a tertiary level multidisciplinary paediatric critical care unit over a 1-year period. The primary outcome measure was the incidence after transfusion of new or progressive multiple organ dysfunction syndrome. Secondary outcome measures included nosocomial infections, intensive care unit length of stay and 28-day mortality. Odds ratios were adjusted for weight, severity of illness, coagulopathy, plasma transfusions prior to admission, need for extracorporeal life support and transfusion of other labile blood products. RESULTS: A total of 831 patients were enrolled, among which 94 (11%) received at least one plasma transfusion. In the latter group of patients, the adjusted odds ratio for an increased incidence of new or progressive multiple organ dysfunction syndrome was 3.2 (P = 0.002). There was also a significant difference in the occurrence of nosocomial infections and intensive care unit length of stay, but no significant difference in the 28-day mortality. CONCLUSIONS: In critically ill children, plasma transfusions seem to be independently associated with an increased occurrence of new or progressive multiple organ dysfunction syndrome, nosocomial infections and prolonged length of stay.

Allergic transfusion reactions from blood components donated by IgA-deficient donors with and without anti-IgA: a comparative retrospective study.

BACKGROUND AND OBJECTIVES: IgA deficiency is common (1/500) and up to 40% of affected individuals will develop anti-IgA. A few studies suggested that passive transfusion of anti-IgA was not associated with an increased risk of allergic reactions. This study was designed to assess the safety of transfusing blood components containing anti-IgA. MATERIALS AND METHODS: IgA-deficient blood donors with and without anti-IgA were identified from Héma-Québec's (HQ) computerized database. IgA deficiency was confirmed by an ELISA method and the presence of anti-IgA by a passive hemagglutination assay. Blood donations from IgA-deficient donors issued to hospitals between March 1999 and December 2004 were retrieved. Medical charts of recipients were reviewed for the occurrence of a suspected transfusion reaction. Presence and nature of transfusion reactions were assessed blindly by an adjudicating committee. RESULTS: A total of 323 IgA-deficient blood products were issued by HQ to 55 hospitals. Of these, 48 agreed to participate [315 blood products (97.5%)]. A total of 272 products were transfused: 174 contained anti-IgA, and 98 did not. Only two minor allergic reactions occurred in each group. Incidence of allergic reactions was 1.15% in the anti-IgA group and 2.04% in the group without anti-IgA (P = 0.91). There was no anaphylactic reaction in either group. CONCLUSIONS: This study indicates that the proportion of allergic reactions does not appear to be greater in recipients of blood components containing anti-IgA compared to recipients of non-anti-IgA-containing components. Allowing donations from IgA-deficient donors with anti-IgA may therefore be contemplated.

Receptive field properties and sensitivity to edges defined by motion in the postero-lateral lateral suprasylvian (PLLS) area of the cat.

The present study investigated the spatial properties of cells in the postero-lateral lateral suprasylvian (PLLS) area of the cat and assessed their sensitivity to edges defined by motion. A total of one hundred and seventeen (117) single units were isolated. First, drifting sinusoidal gratings were used to assess the spatial properties of the cells' receptive fields and to determine their spatial frequency tuning functions. Second, random-dot kinematograms were used to create illusory edges by drifting textured stimuli (i.e. a horizontal bar) against a similarly textured but static background. Almost all the cells recorded in PLLS (96.0%) were binocular, and a substantial majority of receptive fields (79.2%) were end-stopped. Most units (81.0%) had band-pass spatial frequency tuning functions and responded optimally to low spatial frequencies (mean spatial frequency: 0.08 c./degree). The remaining units (19.0%) were low-pass. All the recorded cells responded vigorously to edges defined by motion. The vast majority (96.0%) of cells responded optimally to large texture elements; approximately half the cells (57.3%) also responded to finer texture elements. Moreover, 38.5% of the cells were selective to the width of the bar (i.e., the distance between the leading and the trailing edges). Finally, some (9.0%) cells responded in a transient fashion to leading and to trailing edges. In conclusion, cells in the PLLS area are low spatial frequency analyzers that are sensitive to texture and to the distance between edges defined by motion.

Periodontal and peri-implant diseases: identical or fraternal infections?

Peri-implant diseases (peri-implantitis and peri-implant mucositis) are bacterially driven infections. Peri-implantitis leads to aggressive bone resorption and eventual loss of the implant. Traditionally, peri-implantitis was regarded as microbially similar to periodontitis, and translocation of periodontal pathogens into the peri-implant crevice was considered as a critical factor in disease causation. However, evidence is emerging to suggest that the peri-implant and periodontal ecosystems differ in many important ways. The purpose of this review is to examine the evidence supporting microbial congruence and discordance in these two communities. Current evidence suggests that osseointegrated implants truly create unique microenvironments that force microbial adaptation and selection. Further studies that revisit the "microbial reservoir" hypothesis and identify species that play an etiologic role in peri-implant disease and examine their transmission from teeth are needed.

A reappraisal of exercise electrocardiographic indexes of the severity of ischemic heart disease: angiographic and scintigraphic correlates.

OBJECTIVES: We explored how the exercise electrocardiographic (ECG) indexes generally presumed to signify severe ischemic heart disease (IHD) correlate with coronary angiographic and scintigraphic myocardial perfusion findings. BACKGROUND: In exercise testing, it is generally assumed that the early onset of ST segment depression and its occurrence at a low rate-pressure product (ischemic threshold); the amount of maximal ST segment depression; and a horizontal or downsloping ST segment and its prolonged recovery after exercise signify more severe IHD. However, the relation of these indexes to coronary angiographic and exercise myocardial perfusion findings in patients with IHD is unclear. METHODS: We prospectively carried out a symptom-limited 12-lead Bruce protocol thallium-201 single-photon emission computed tomographic (SPECT) exercise test in 66 consecutive subjects with stable angina, > or = 70% stenosis of at least one coronary artery, normal rest ECG and left ventricular wall motion and a prior positive exercise ECG. The above ECG indexes, vessel disease (VD), a VD score and the quantitative thallium-SPECT measures of the extent, maximal deficit and redistribution gradient of the perfusion abnormality were characterized. RESULTS: Maximal ST segment depression could not differentiate the number of diseased vessels; was not related to VD score, maximal thallium deficit or redistribution gradient; but was related to the extent of perfusion abnormality (r = 0.29, 95% confidence interval [CI] 0.08 to 0.52, p = 0.02). Time of onset of ST segment depression correlated inversely only with VD (r = -0.22, 95% CI -0.44 to -0.05, p < 0.05), whereas the ischemic threshold had low inverse correlation only with VD score (r = -0.25, 95% CI -0.47 to -0.01, p < 0.05) and the redistribution gradient (r = -0.33, 95% CI -0.53 to -0.10, p < 0.01). A horizontal or downsloping compared with an upsloping ST segment did not demonstrate more severe angiographic and scintigraphic disease. Recovery time did not correlate with angiographic and scintigraphic findings, and correlations between angiographic and scintigraphic findings were also low or absent. CONCLUSIONS: In this homogeneous study group, the exercise ECG indexes did not necessarily signify more severe IHD by angiographic and scintigraphic criteria. Lack of concordance between the exercise ECG, angiography and myocardial scintigraphy suggests that these diagnostic modalities examine different facets of myocardial ischemia, underscoring the need for caution in the interpretation of their results.

Attenuation of myocardial ischemia with repeated exercise in subjects with chronic stable angina: relation to myocardial contractility, intensity of exercise and the adenosine triphosphate-sensitive potassium channel.

OBJECTIVES: This study characterized the attenuation of myocardial ischemia observed with re-exercise to determine whether: 1) a differing exercise intensity modifies this attenuation; 2) it could be explained by contractile down-regulation or stunning; 3) it is mediated by activation of ATP-sensitive potassium channels (K+-ATP). BACKGROUND: Subjects with ischemic heart disease (IHD) frequently note less angina with re-exercise after a brief rest. Potential mechanisms of this 'warm-up' phenomenon have been little explored. METHODS: IHD subjects with a positive exercise test were studied. Groups I and II (12 subjects each) underwent 2 successive Naughton protocol exercise echocardiography tests (with 1 min instead of 2 min stages for Group II). Group D (10 subjects) had type II diabetes, were on > or =10 mg daily of the K+-ATP blocker, glibenclamide, and underwent the group I exercise protocol. The ischemic threshold or rate-pressure product at 1 mm ST segment depression, ST depression corresponding to the peak rate-pressure product of the first exercise (maximum ST depression equivalent), and left ventricular wall motion indexes before and immediately after each exercise were analyzed. RESULTS: Exercise-induced myocardial ischemia with re-exercise was similarly attenuated in groups I, II, and D. The ischemic threshold was raised by nearly 20% with re-exercise (p=0.001, p=0.02, and p=0.02, respectively) and the maximum ST depression equivalent was nearly halved on re-exercise (p=0.005, p=0.006, and p=0.001, respectively). Exercise-induced wall motion dysfunction was attenuated with re-exercise. In group I, wall motion returned to the initial baseline score prior to exercise 2, whereas in the more intense protocol of group II, wall motion dysfunction persisted prior to exercise 2. CONCLUSIONS: Thus, the attenuation of myocardial ischemia observed with re-exercise appears to be independent of the intensity of the exercise protocol and is not explained by down-regulation of myocardial contractility induced by the initial ischemic stimulus. Since results were similar in diabetic subjects on robust doses of glibenclamide, this phenomenon does not appear to be mediated by K+-ATP activation.

Effect of gender, sex hormones, time variables and physiological urinary pH on apparent CYP2D6 activity as assessed by metabolic ratios of marker substrates.

The effects of gender, time variables, menstrual cycle phases, plasma sex hormone concentrations and physiologic urinary pH on CYP2D6 phenotyping were studied using two widely employed CYP2D6 probe drugs, namely dextromethorphan and metoprolol. Phenotyping on a single occasion of 150 young, healthy, drug-free women and men revealed that the dextromethorphan: dextrorphan metabolic ratio (MR) was significantly lower (P < 0.0001) in 56 female extensive metabolizers (0.008+/-0.021) compared to 86 male extensive metabolizers (0.020 +/-0.040). Urinary pH was a significant predictor of dextromethorphan: dextrorphan MRs in men and women (P < 0.001). Once-a-month phenotyping with dextromethorphan of 12 healthy young men (eight extensive metabolizers and four poor metabolizers) over a 1-year period, as well as every-other-day phenotyping with dextromethorphan of healthy, pre-menopausal women (10 extensive metabolizers and 2 poor metabolizers) during a complete menstrual cycle, did not follow a particular pattern and showed similar intrasubject variability ranging from 24.1% to 74.5% (mean 50.9%) in men and from 20.5% to 96.2% (mean 52.0%) in women, independent of the CYP2D6 phenotype (P = 0.342). Using metoprolol as a probe drug, considerable intrasubject variability (38.6+/- 12.0%) but no correlation between metoprolol: alpha-hydroxymetoprolol MRs and pre-ovulatory, ovulatory and luteal phases (mean +/- SD metoprolol: a-hydroxymetoprolol MRs: 1.086+/- 1.137 pre-ovulatory; 1.159+/-1.158 ovulatory and 1.002+/-1.405 luteal phase; P> 0.9) or 17beta-oestradiol, progesterone or testosterone plasma concentrations was observed. There was a significant inverse relationship between physiologic urinary pH and sequential dextromethorphan: dextrorphan MRs as well as metoprolol: alpha-hydroxymetoprolol MRs in men and women, with metabolic ratios varying up to six-fold with metoprolol and up to 20-fold with dextromethorphan (ANCOVA P < 0.001). We conclude that apparent CYP2D6 activity is highly variable, independent of menstrual cycle phases, sex hormones, time variables or phenotype. Up to 80% of the observed variability can be explained by variations of urinary pH within the physiological range. An apparent phenotype shift as a result of variations in urinary pH may be observed in individuals who have metabolic ratios close to the population antimode.

Hypertension in women.

Hypertension in women has received little attention in comparison to men. There are only a handful of studies focusing on women with hypertension. Nevertheless, the data provide some information on the prevalence of hypertension in women, complications and the effectiveness of treatment. The Framingham Study showed that blood pressure (BP) increased with age in both men and women. The Hypertension Detection and Follow-up Program study demonstrated that hypertension was much more prevalent in men than women. However, in the postmenopausal group more than half were hypertensive. High BP is prevalent in older women. In absolute values, the complication rate is lower in women than in men but increases with age. At all levels of BP, the morbidity and mortality associated with BP is lower in women than men. Nevertheless, there is a five- to sixfold increase in risk in hypertensive compared with normotensive women. Furthermore, hypertensive women with a myocardial infarction have a worse prognosis than men. No study data using newer agents such as calcium channel blockers and angiotensin-converting enzyme inhibitors are available yet. Since antihypertensive treatment appears to be effective in smokers, cessation of smoking is a very important intervention. Studies such as the European Working Party on Hypertension in Elderly, Systolic Hypertension in Elderly, Swedish Trial of Old Patients with Hypertension, and Medical Research Council 1992 have recruited patients 60 years of age and older, mainly women. These trials have shown that in the elderly hypertensive all-cause mortality is reduced by 30%, stroke by 33%, congestive heart disease mortality by 20% and heart failure by 40% to 50% with treatment. However, even these newer trials have used the so-called "old medications'. Studies using "newer drugs' are in progress.

Impact of systolic and diastolic blood pressure on ischemic vascular diseases in French-Canadian men from 1974 to 1990.

The relationships of systolic and diastolic blood pressure (BP) to ischemic heart disease (IHD), intermittent claudication (IC) and stroke were evaluated in 4385 men (aged 35 to 64 years in 1973) clinically free from these vascular diseases at entry and followed for 16 years. The mean of two readings measured in 1973-74 was used as the baseline BP. The cut-of for quintile 5 was systolic BP greater than 152 mmHg and diastolic BP greater than 92 mmHg. Relative risks (RR) were adjusted for main risk factors and calculated separately for systolic and diastolic BP. From 1974-90, 1120 first ischemic vascular events were documented: 792 IHD, 216 IC and 112 strokes. The incidences of each ischemic vascular disease increased, starting at quintile 4, for either systolic or diastolic BP. For systolic BP, the adjusted RR of quintile 5 compared with quintile 1 were 1.8 for IHD (95% confidence interval 1.4 to 2.2), 2.7 for IC (1.8 to 4.2) and 3.8 for stroke (2.1 to 7.0); for diastolic BP, the RR were 1.8 for IHD (1.5 to 2.3), 1.5 for IC (1.0 to 2.1) and 3.5 for stroke (2.0 to 6.4). For IHD, the RR of BP were similar for angina and myocardial infarction, and more pronounced for coronary death. In this population, elevated BP constitutes an important risk factor not only for stroke, but also for the main manifestations of IHD and IC. The impact of systolic BP was at least as significant as that of diastolic BP on these ischemic vascular events.

Importance of outside hospital mortality as a first acute ischemic heart event: the Quebec Cardiovascular Study.

Among 4371 men aged 35 to 64 in 1973 who were randomly selected, living in Quebec City suburbs, without clinical evidence of ischemic heart disease (IHD) at entry and followed for 16 years, 426 had a first acute IHD event; of these, 296 had a nonfatal myocardial infarction (MI), 50 a fatal MI (death within four weeks of the acute event) and 80 an early death, ie, they died before the diagnosis of MI was made. Among these 80 early deaths attributed to IHD in the absence of any other apparent cause, 55 men died within 1 h from the onset of symptoms or were found dead in their bed (group A) while 25 died more than 1 h after the onset of symptoms (group B). In this population, a first acute IHD event carried a 31% (130 of 426) case fatality within the first four weeks. Groups A and B accounted for 42% (55 of 130) and 19% (25 of 130) of the total acute ischemic mortality, respectively. As expected, fatal events increased with age, but the proportion of early deaths over the total IHD mortality was as frequent in younger men as in older men. Smoking, increased systolic and diastolic blood pressure and serum cholesterol were associated with increased nonfatal events. A similar association, except for serum cholesterol, was observed for all fatal events. No significant risk factor profile differentiated early from late fatal events. In conclusion, in this population, nearly a third of men with a first IHD event died, most of them outside the hospital. None of the main established risk factors differentiated men with a fatal MI from those with an early death.

First coronary heart disease event rates in relation to major risk factors: Quebec cardiovascular study.

The incidence of first coronary heart disease (CHD) events was evaluated prospectively in relation to the baseline measurements of systolic and diastolic blood pressure, serum cholesterol, smoking status and education in a cohort of 4576 Quebec men aged 35 to 64 and free from CHD at entry in 1974. From 1974 to 1986, 603 first CHD events were documented. The most frequent first manifestation was angina (6.7/1000 person-years) followed by nonfatal myocardial infarction (4.7/1000) and CHD death 2.2/1000). There was a positive relationship between the first CHD event and systolic (Z = 4.67) and diastolic (Z = 6.50) blood pressure. This relation was observed for angina, nonfatal myocardial infarction and CHD death. Serum cholesterol was also related to all events (Z = 4.99) but more specifically to angina and nonfatal myocardial infarction. Cigarette smoking was significantly related to first CHD manifestations. This relationship for specific CHD events was observed in men who smoked more than 20 cigarettes per day. Men who discontinued smoking one year before the study had a risk not different from those who never smoked. No relationship was observed between years of schooling and CHD events. Blood pressure, cholesterol and smoking constituted nearly two-thirds of the attributable risk of first CHD events.

Smoking, alcohol consumption, lipid and lipoprotein levels.

The lipid profiles of 1165 French Canadian men (aged 42 to 59 years) were studied and related to drinking and smoking habits. Alcohol consumption and smoking were closely related, smokers consuming twice as much alcohol as non-smokers. When relative body weight, total cholesterol, triglyceride and alcohol consumption were controlled in a covariate analysis, plasma levels of high density lipoprotein (HDL) cholesterol, HDL2 and HDL3 differed significantly between smokers, ex-smokers and nonsmokers. Ex-smokers had higher levels of HDL cholesterol than nonsmokers who had higher levels than smokers. The higher levels of HDL in ex-smokers could be explained by the confounding effects of alcohol intake. Alcohol users had significantly higher levels of HDL cholesterol, HDL2 and HDL3 than nondrinkers. Men who drank the equivalent of more than 3 ounces of absolute alcohol per week had significantly higher levels of HDL cholesterol and HDL3 than those who drank less than 3 ounces or did not drink at all. HDL2 levels were only significantly different between nondrinkers and those who consumed more than 3 ounces per week. These results show that smoking and alcohol have strong but opposing effects on HDL and its subfractions in middle-aged French Canadian men.

Total and coronary heart disease mortality in relation to major risk factors--Quebec cardiovascular study.

The relationships of blood pressure, smoking, serum cholesterol and education levels on total and coronary artery disease (CAD) mortality were evaluated in 4576 Quebec men aged 35 to 64 years, free from overt CAD at entry and followed for 12 years. From January 1974 to January 1986, there were 417 deaths, 131 due to CAD. A progressive increase in total and CAD mortality was observed from quintile 3 to 5 for both systolic and diastolic blood pressure. In comparison to quintile 1, the adjusted relative risks of quintiles 4 and 5 for systolic blood pressure were significantly elevated (2 P less than 0.01), being 1.5 and 2.0 for total mortality, and 2.6 and 3.5 for CAD mortality, respectively. The relative risks of quintiles 4 and 5 for diastolic blood pressure were also significantly elevated (2 P less than 0.04), being 1.5 and 1.6 for total mortality and 1.9 and 2.7 for CAD mortality, respectively. In comparison to those who never smoked, the relative risks of smoking one to 20, and 21 and more cigarettes per day, were 2.1 (2 P less than 0.003) and 3.1 (2 P less than 0.0001) for overall mortality, and 2.2 (2 P less than 0.08) and 3.5 (2 P less than 0.002) for CAD mortality. Men who had discontinued smoking at least one year before the study, had a relative risk not different from those who had never smoked. Serum cholesterol and education levels were not significantly associated with total or CAD mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased risk of myocardial infarction associated with angiotensin-converting enzyme gene polymorphism is age dependent.

The angiotensin-converting enzyme (ACE) gene is a candidate genetic locus for coronary artery disease (CAD). Studies investigating the relationship between the ACE-insertion/deletion (I/D) gene polymorphism and myocardial infarction (MI) have been inconsistent. The authors hypothesized that age may be an important modulating factor in this relationship. ACE-I/D allele and genotype distribution was determined in 3 groups: 104 men with a first MI at a young age (≤45 years old), 271 healthy young men (≤30 years old), and 28 healthy elderly men (>65 years old). All participants were French descendants from Quebec City, Canada. Frequency distribution of the ACE alleles and genotypes was similar among the healthy young, the healthy elderly, and the MI patients (P > .05). However, when considering the age at the time of the MI (≤40, ≤35, or ≤30 years old), a significant age-dependent effect with the prevalence of the ACE-DD genotype was found, as it increased by 22%, 61%, and 157%, respectively, compared with the healthy young group (P < .05). Similar observations were obtained versus the healthy elderly men (P < .05). The ACE-I/D polymorphism seems to be a genetic risk factor for MI in young men and becomes an important modulator of MI risk at a young age.