High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men.

BACKGROUND. Iron can induce lipid peroxidation in vitro and in vivo in humans and has promoted ischemic myocardial injury in experimental animals. We tested the hypothesis that high serum ferritin concentration and high dietary iron intake are associated with an excess risk of acute myocardial infarction. METHODS AND RESULTS. Randomly selected men (n = 1,931), aged 42, 48, 54, or 60 years, who had no symptomatic coronary heart disease at entry, were examined in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in Eastern Finland between 1984 and 1989. Fifty-one of these men experienced an acute myocardial infarction during an average follow-up of 3 years. On the basis of a Cox proportional hazards model adjusting for age, examination year, cigarette pack-years, ischemic ECG in exercise test, maximal oxygen uptake, systolic blood pressure, blood glucose, serum copper, blood leukocyte count, and serum high density lipoprotein cholesterol, apolipoprotein B, and triglyceride concentrations, men with serum ferritin greater than or equal to 200 micrograms/l had a 2.2-fold (95% CI, 1.2-4.0; p less than 0.01) risk factor-adjusted risk of acute myocardial infarction compared with men with a lower serum ferritin. An elevated serum ferritin was a strong risk factor for acute myocardial infarction in all multivariate models. This association was stronger in men with serum low density lipoprotein cholesterol concentration of 5.0 mmol/l (193 mg/dl) or more than in others. Also, dietary iron intake had a significant association with the disease risk in a Cox model with the same covariates. CONCLUSIONS. Our data suggest that a high stored iron level, as assessed by elevated serum ferritin concentration, is a risk factor for coronary heart disease.     

Reduction in serum total cholesterol and risks of coronary events and cerebral infarction in Japanese men: the Kyushu Lipid Intervention Study.

Lowering serum total cholesterol is shown to decrease the risk of coronary heart disease (CHD) in Western countries,but evidence is limited regarding cerebral infarction (CI). The present study used the Kyushu Lipid Intervention Study to examine the risks of CHD events and CI in relation to reduction in serum total cholesterol. Subjects were 4,615 men aged 45-74 years with serum total cholesterol of 220 mg/dl (5.68 mmol/L) or greater who had no history of CHD events or stroke. CHD events and CI numbered 125 and 92, respectively, in a 5-year follow-up. After adjustment for potential confounding factors, the relative risks of CHD events and CI for 15% or greater reduction in total cholesterol, compared with less than 5% reduction, were 0.78 (95% confidence limit [CL]0.46-1.32) and 0.39 (95% CL 0.22-0.69), respectively. As compared with on-treatment cholesterol levels of 240 mg/dl (6.20 mmol/L)or higher, the risk of CHD events was approximately 50% lower across 3 categories below 240 mg/dl (6.20 mmol/L), and that of CI was 70%lower at 2 categories below 220 mg/dl (5.68 mmol/L). Lowering serum total cholesterol below 220 mg/dl (5.68 mmol/L) seems desirable with regard to the prevention of CI.     

HDL cholesterol efflux capacity and incident cardiovascular events

Background It is unclear whether high-density lipoprotein(HDL) cholesterol concentration plays a causal role in atherosclerosis. A more important factor may be HDL cholesterol efflux capacity, the ability of HDL to accept cholesterol from macrophages, which is a key step in reverse cholesterol transport. We investigated the epidemiology of cholesterol efflux capacity and its association with incident atherosclerotic cardiovascular disease outcomes in a large, multiethnic population cohort.Methods We measured HDL cholesterol level, HDL particle concentration, and cholesterol efflux capacity at baseline in 2924 adults free from cardiovascular disease who were participants in the Dallas Heart Study, a probabilitybased population sample. The primary end point was atherosclerotic cardiovascular disease, defined as a first nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization or death from cardiovascular causes. The median follow-up period was 9.4 years.Results In contrast to HDL cholesterol level, which was associated with multiple traditional risk factors and metabolic variables, cholesterol efflux capacity had minimal association with these factors. Baseline HDL cholesterol level was not associated with cardiovascular events in an adjusted analysis(hazard ratio, 1.08;95% confidence interval [CI], 0.59 to 1.99). In a fully adjusted model that included traditional risk factors,HDL cholesterol level, and HDL particle concentration, there was a 67% reduction in cardiovascular risk in the highest quartile of cholesterol efflux capacity versus the lowest quartile(hazard ratio, 0.33; 95% CI, 0.19 to 0.55). Adding cholesterol efflux capacity to traditional risk factors was associated with improvement in discrimination and reclassification indexes.Conclusions Cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport,was inversely associated with the incidence of cardiovascular events in a population-based cohort.(From: N Engl J Med 2014; 371:2383-2393 December 18, 2014DOI: 10.1056 / NEJMoa1409065)     

Clusters of metabolic risk factors predict cardiovascular events in hypertension with target-organ damage: the LIFE study

The relation of metabolic syndrome (MetS) with cardiovascular outcome may be less evident when preclinical cardiovascular disease is present. We explored, in a post hoc analysis, whether MetS predicts cardiovascular events in hypertensive patients with electrocardiographic left ventricular hypertrophy (ECG-LVH) in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. MetS was defined by >or=2 risk factors plus hypertension: body mass index >or=30 kg/m(2), high-density lipoprotein (HDL)-cholesterol <1.0/1.3 mmol/l (<40/50 mg/dl) (men/women), glucose >or=6.1 mmol/l (>or=110 mg/dl) fasting or >or=7.8 mmol/l (>or=140 mg/dl) nonfasting or diabetes. Cardiovascular death and the primary composite end point (CEP) of cardiovascular death, stroke and myocardial infarction were examined. In MetS (1,591 (19.3%) of 8,243 eligible patients), low HDL-cholesterol (72%), obesity (77%) and impaired glucose (73%) were similarly prevalent, with higher blood pressure, serum creatinine and Cornell product, but lower Sokolow-Lyon voltage (all P<0.001). After adjusting for baseline covariates, hazard ratios for CEPs and cardiovascular death (4.8+/-1.1 years follow-up) were 1.47 (95% confidence interval (CI), 1.27-1.71)- and 1.73 (95% CI, 1.38-2.17)-fold higher with MetS (both P<0.0001), and were only marginally reduced when further adjusted for diabetes, obesity, low HDL-cholesterol, non-HDL-cholesterol, pulse pressure and in-treatment systolic blood pressure and heart rate. Thus, MetS is associated with increased cardiovascular events in hypertensive patients with ECG-LVH, independently of single cardiovascular risk factors.     

Smoking, blood pressure and serum cholesterol as risk factors of acute myocardial infaction and death among men in Eastern Finland

The impact of smoking, serum cholesterol and blood pressureon the risk of acute myocardial infarction and death due toall causes and cardiovascular diseases was studied in a randomsample of men aged 35 to 59 years from the North Karelia andKuopio counties of Eastern Finland. This is an area with anexceptionally high incidence of coronary heart disease. Altogether,4034 men were studied with a participation rate of 92%. Thesemen were followed-up with a myocardial infarction register anddeath certificate data. During the first five years 256 deathsoccurred among all subjects. There were 66 acute myocardialinfarctions in the North Karelian men reporting no recent coronaryheart disease. Smoking, elevated serum cholesterol and bloodpressure were independently and jointly related to an increasedrisk of acute myocardial infarction and death due to all causesand to cardiovascular disease. Smokers had a 2–3-foldage-adjusted risk of acute myocardial infarction, a 2-2-foldrisk of any death and a 2.1-fold risk of cardiovascular deathcompared with non-smokers. The age-adjusted risk ratios forsystolic blood pressure of 160 mm Hg or more were 1.3, 1.4 and1.9 and those for serum cholesterol at least 8 mmol/l (309 mg/100ml) 2.6, 1.5 and 2.6 concerning myocardial infarction, all deathsand cardiovascular deaths, respectively. All risk ratios exceptthat of systolic blood pressure for acute myocardial infarctionwere significant at levels of at least P < 0.05     

C-reactive protein, cardiovascular risk factors and the association with myocardial infarction in men

OBJECTIVES: This study had three objectives: first, to investigate the association of C-reactive protein levels and myocardial infarction amongst men; secondly, to study the associations of C-reactive protein levels with cardiovascular risk factors; and thirdly, to adjust the risk of myocardial infarction for such factors. DESIGN AND SUBJECTS: A case-control study including 560 patients with a first myocardial infarction who had survived at least 6 months, plus 646 control subjects. RESULTS: Patients had significantly higher levels of C-reactive protein (mean 2.2 mg L-1) than control subjects (mean 1.7 mg L-1; P < 0.001). Persons in the highest quintile of C-reactive protein had an unadjusted 1.9-fold increased risk of myocardial infarction compared with persons in the lowest quintile (odds ratio 1.9, 95% CI: 1.3-2.7). C-reactive protein was, in addition to smoking, associated with several cardiovascular risk factors: age, obesity, diabetes, blood pressure, triglycerides and inversely associated to HDL cholesterol. Adjustment for these variables, especially for total cholesterol, HDL cholesterol and triglycerides, substantially decreased the risk of myocardial infarction for persons in the highest quintile of C-reactive protein, compared to those in the lowest quintile, to 1.3 (95% CI: 0.9-1.9). CONCLUSIONS: Our findings confirm previous reports that C-reactive protein predicts the risk of myocardial infarction. However, this association does not appear to be causal, since the increase in risk can to a large extent be explained by the presence of other cardiovascular risk factors.     

Clinical evaluation of plasma high-density lipoprotein subfractions (HDL2, HDL3) in non-insulin-dependent diabetics with coronary artery disease

STATEMENT OF THE PROBLEM: Low levels of high-density lipoprotein cholesterol (HDL-C) have a strong association with coronary artery disease (CAD) in patients with non-insulin-dependent diabetes mellitus (NIDDM). In this study, we tried to evaluate whether one or both of the major HDL subclasses (HDL2, HDL3) is strongly associated with the risk of CAD in NIDDM subjects. METHODS: The separation of HDL subclasses was carried out by ultracentrifugation in a Beckman Airfuge. HDL2 subclass was isolated from the supernatant and its cholesterol content was measured enzymatically. Plasma HDL3 cholesterol was calculated as the difference between results for total HDL cholesterol and HDL2 cholesterol. RESULTS: NIDDM patients with CAD had significantly higher triglyceride levels compared to either control (217.09+/-55.04 versus 89.62+/-31.29 mg/dl, P=.001) or CAD patients without NIDDM (217.09+/-55.04 versus 156.28+/-46.39 mg/dl, P<.05). However, in the diabetic patients with CAD, there was a statistically significant decrease in HDL cholesterol (39.63+/-8.59 versus 55.86+/-13.49 mg/dl, P<.01), HDL2 cholesterol (8.74+/-3.28 versus 16.95+/-5.73 mg/dl, P<.001), and HDL3 cholesterol (31.23+/-7.41 versus 38.91+/-8.93 mg/dl, P<.05) in comparison to nondiabetic controls. Moreover, in the comparison between non-insulin-dependent diabetics with CAD and CAD subjects without NIDDM, HDL cholesterol (39.63+/-8.59 versus 46.13+/-6.33 mg/dl, P<.05) and HDL2 cholesterol (8.74+/-3.28 versus 11.84+/-4.01 mg/dl, P<.02) were significantly reduced, while HDL3 cholesterol levels were (31.23+/-7.41 versus 34.29+/-7.94 mg/dl, P=.92) unaltered. Additionally, the percentage reduction of cholesterol in HDL2 fraction was proportionately greater than the decrease in HDL3 subclass in both comparisons. Moreover, in NIDDM with CAD, HDL cholesterol was reduced by 29% and 14%, HDL2 cholesterol by 48% and 26%, and HDL3 cholesterol by 20% and 9%, compared relatively to controls and CAD subjects without NIDDM. CONCLUSIONS: In conclusion, HDL2 is the more variable subclass and reflects changes in HDL. This suggests that the protective role of total HDL against CAD is mainly mediated through HDL2 fraction. Therefore, HDL2 might be a better predictor of coronary heart disease than total HDL, in non-insulin-dependent diabetes mellitus.     

Relationship of glucose and insulin levels to the risk of myocardial infarction: a case-control study

OBJECTIVE: To assess the relationship between dysglycemia and myocardial infarction in nondiabetic individuals. BACKGROUND: Nondiabetic hyperglycemia may be an important cardiac risk factor. The relationship between myocardial infarction and glucose, insulin, abdominal obesity, lipids and hypertension was therefore studied in South Asians-a group at high risk for coronary heart disease and diabetes. METHODS: Demographics, waist/hip ratio, fasting blood glucose (FBG), insulin, lipids and glucose tolerance were measured in 300 consecutive patients with a first myocardial infarction and 300 matched controls. RESULTS: Cases were more likely to have diabetes (OR 5.49; 95% CI 3.34, 9.01), impaired glucose tolerance (OR 4.08; 95% CI 2.31, 7.20) or impaired fasting glucose (OR 3.22; 95% CI 1.51, 6.85) than controls. Cases were 3.4 (95% CI 1.9, 5.8) and 6.0 (95% CI 3.3, 10.9) times more likely to have an FBG in the third and fourth quartile (5.2-6.3 and >6.3 mmol/1); after removing subjects with diabetes, impaired glucose tolerance and impaired fasting glucose, cases were 2.7 times (95% CI 1.5-4.8) more likely to have an FBG >5.2 mmol/l. A fasting glucose of 4.9 mmol/l best distinguished cases from controls (OR 3.42; 95% CI 2.42, 4.83). Glucose, abdominal obesity, lipids, hypertension and smoking were independent multivariate risk factors for myocardial infarction. In subjects without glucose intolerance, a 1.2 mmol/l (21 mg/dl) increase in postprandial glucose was independently associated with an increase in the odds of a myocardial infarction of 1.58 (95% CI 1.18, 2.12). CONCLUSIONS: A moderately elevated glucose level is a continuous risk factor for MI in nondiabetic South Asians with either normal or impaired glucose tolerance.     

Low serum apolipoprotein A-I in acute myocardial infarction survivors with normal HDL cholesterol

High density lipoprotein (HDL) cholesterol, apolipoprotein A-I (apo A-I), gamma-glutamyl-transferase, testosterone and oestradiol were determined in plasma in non-diabetic males who had survived an acute myocardial infarction (AMI) before the age of 60. They also had serum levels of cholesterol below 7.0 mmol/l 1 year after the AMI. On the basis of diastolic blood pressure they were subdivided into 2 groups with diastolic blood pressures below 90 mm Hg (n = 39), and with or above 95 mm Hg (n = 21) and then compared with an age-matched male non-diabetic reference group (n = 32). There were no significant differences in the levels of HDL cholesterol, gamma-glutamyl-transferase, and sex hormones between the AMI groups and the reference group. Reduced plasma levels of apo A-I were found in the AMI groups.     

Deficiency of serum cholesteryl-ester transfer activity in patients with familial hyperalphalipoproteinaemia

Lipoprotein patterns and cholesteryl ester transfer activity (CETA) were examined in 2 patients with familial hyperalphalipoproteinaemia (FHALP). The proband was a healthy 58-year-old Japanese male who had an HDL cholesterol of 7.83 mmol/l (301 mg/dl). His sister's HDL cholesterol was 4.52 mmol/l (174 mg/dl), which suggested that both were homozygous carriers of FHALP. In both subjects HDL showed a high cholesterol/apo A-I ratio and appeared to be a larger-sized particle than normal HDL on agarose gel chromatography. Two of the proband's children showed higher HDL cholesterol levels (1.74 mmol/l, 2.16 mmol/l) than normal, but another 2 children showed normal levels (1.48 mmol/l, 1.40 mmol/l). However, the ratios of HDL cholesterol to total cholesterol and to apo A-I in all children were higher than normal. These data suggest, but do not prove, that all his children were heterozygotes. Apo B levels in all of the family members studied were lower than normal (47-80 mg/dl). Deceased members of the same family had not died from cardiovascular disease. Cholesteryl-ester transfer activity was studied in both patients. When serum or lipoprotein deficient serum (d greater than 1.21) and [3H]cholesteryl ester labelled HDL3 were incubated in the presence of an LCAT inhibitor, there was no evidence of cholesteryl ester transfer from HDL to VLDL and/or LDL, unlike normal subjects. The deficiency of CETA in these patients with FHALP presumably accounted for the increase in particle size and cholesterol enrichment of HDL.     

Change in high-density lipoprotein cholesterol and risk of subsequent hospitalization for coronary artery disease or stroke among patients with type 2 diabetes mellitus

The association between the changes in high-density lipoprotein (HDL) cholesterol and the risk of cardiovascular (CVD) or cerebrovascular hospitalization among patients with type 2 diabetes remains unclear. We conducted a retrospective observational cohort study of 30,067 members of the Kaiser Permanente Northwest and Georgia regions, who had type 2 diabetes and 2 HDL cholesterol measurements 6 to 24 months apart in 2001 to 2006. We followed up the cohort for ≤8 years (through 2009) to determine whether the change in HDL cholesterol was associated with subsequent CVD hospitalization. We examined the HDL cholesterol change continuously and by 3 categories: HDL cholesterol increased ≥6.5 mg/dl, decreased ≥6.5 mg/dl, or remained within ±6.4 mg/dl. The Cox regression models were adjusted for the baseline HDL cholesterol and demographic and clinical risk factors. During a mean follow-up of 55.8 ± 23.8 months, 3,023 patients (10.1%) experienced a CVD hospitalization. After multivariate adjustment, each 5 mg/dl of baseline HDL cholesterol was significantly associated with a 6% lower CVD hospitalization risk (hazard ratio 0.94 per 5 mg/dl, 95% confidence interval 0.92 to 0.95, p <0.0001) and each 5-mg/dl increase in HDL cholesterol was associated with a 4% CVD risk reduction (hazard ratio 0.96, 95% confidence interval 0.94 to 0.99, p <0.003). In the categorical analysis, a ≥6.5-mg/dl HDL cholesterol decrease was associated with an 11% increased CVD risk (hazard ratio 1.11, 95% confidence interval 1.00 to 1.24, p = 0.047) and a ≥6.5-mg/dl increase was associated with an 8% CVD risk reduction (hazard ratio 0.92, 95% confidence interval 0.84 to 1.01, p = 0.077) relative to those with stable HDL cholesterol. In conclusion, our results add to the growing body of evidence that increasing the HDL cholesterol levels might be an important strategy for CVD risk reduction. The prevention of HDL cholesterol decreases could be equally important.     

Serum HDL cholesterol values are associated with apoB-containing lipoprotein metabolism and triglyceride-body fat interrelation in young Japanese men

Serum levels of total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein (apo) AI, ApoB, ApoE and body fat were measured in 226 fasting male Japanese college students aged 18 to 20 years. They were normolipidemic (total cholesterol: 169±31 mg/dl, triglyceride: 56±25 mg/dl) and their HDL cholesterol concentrations were high (61±13 mg/dl). An HDL cholesterol value <35 mg/dl was observed in only one student (0.4%). In contrast, 112 men (49.6%) had an HDL cholesterol level ≥60 mg/dl. Even in this normolipidemic group, as compared with students in a top HDL cholesterol tertile (HDL cholesterol; 75±9 mg/dl), students in a lower HDL cholesterol tertile (HDL cholesterol; 48±5 mg/dl) had significantly increased serum levels of LDL cholesterol (103±30 vs. 91±26 mg/dl), triglyceride (68±30 vs. 45±16 mg/dl) and apoB (83±20 vs 73±17 mg/dl). In addition, they had greater body mass index (23.2±3.6 vs. 20.6±2.5 kg/m²) and greater percent body fat (20.2±6.2 vs. 16.2±4.2%) determined using a bioelectrical impedance analyzer. HDL cholesterol levels were much more strongly related to triglyceride (r=−0.37) than was apoAI (r=−0.13). In stepwise multiple regression analysis in 184 nonsmokers, apoE, apoB and fat mass explained 21% of apoAI variability. Triglyceride in addition to these three parameters explained 41% of HDL cholesterol variability. These results suggest that serum levels of HDL cholesterol are associated with metabolism of apoB-containing lipoproteins as well as triglyceride-body fat interrelationship.     

Effect of the metabolic syndrome and hyperuricemia on outcome in patients with coronary artery disease (from the Bezafibrate Infarction Prevention Study)

Hyperuricemia appears to be related to metabolic syndrome (MS), but its impact on cardiovascular risk in patients with MS is unclear. We evaluated the impact of hyperuricemia on cardiovascular risk in patients with MS. Of 2,963 patients with coronary artery disease enrolled in the Bezafibrate Infarction Prevention study, 1,410 had MS, as established by the presence of ≥3 of the following 5 criteria: serum fasting glucose >110 mg/dl, triglycerides >150 mg/dl, high-density lipoprotein cholesterol <40 mg/dl in men and <50 mg/dl in women, systolic and diastolic blood pressures >130 and 80 mm Hg, respectively, and body mass index >28 kg/m2. The remaining 1,553 patients had no MS. Primary end points were defined as occurrence of acute myocardial infarction or sudden cardiac death. Hyperuricemia was defined as serum uric acid levels >7.0 mg/dl in men and >6.0 mg/dl in women, respectively. Higher rate of primary end point was noted in hyperuricemic patients (n = 284) versus normouricemic patients (n = 1,126) with MS (20.1% and 15.3%, respectively, p = 0.05). After adjustment for age, gender, smoking, diabetes, previous myocardial infarction, hypertension, New York Heart Association classes II to IV, estimated glomerular filtration rate, body mass index, total cholesterol, triglycerides, diuretics, antiplatelets, angiotensin-converting enzyme inhibitors, β blockers, and bezafibrate treatment, hyperuricemic patients with MS demonstrated significantly higher risk for the primary end point compared to normouricemic patients with MS (hazard ratio 1.45, 95% confidence interval 1.00 to 2.17, p = 0.05). In conclusion, hyperuricemia is associated with increased risk of myocardial infarction and sudden cardiac death in patients with MS.     

Timolol maleate and HDL cholesterol after myocardial infarction

Myocardial infarction, serum lipids, HDL cholesterol, adrenergicbetareceptor blockade. The influence of long-term timolol treatmenton plasma lipids was analysed in cohorts of the Norwegian timololmulticentre study. The prognostic importance of high-densitylipoprotein (HDL) cholesterol concentration after myocardialinfarction was also examined. One year timolol treatment wasrelated to a significant reduction in HDL cholesterol levels,from 1.32 mmol l-1 to L26mmoll-1 (P<0.05). After one yearthe HDL cholesterol levels were significantly lower in the timololtreated patients (1.26 mmol l-1) than in the placebo treatedpatients (1.32 mmol l-1, P<0.01). However, the HDL cholesterolvalues after myocardial infarction had no prognostic importance,and in the placebo group total mortality was the same in patientswith low HDL cholesterol ( < 1.25mmol l-1) and high HDL cholesterol(> 1.25mmoll-1), respectively 15.0% and 14.8%. Timolol treatmentwas related to a reduction in mortality both in patients withlow (24%, NS) and with high (43%, P < 0.05) HDL cholesterollevels. Thus, any deleterious effects of timolol on serum lipidsdid not attenuate its protective effect on the damaged myocardium.     

Studies on the relationship between the cholesterol content in total high density lipoprotein and its subfractions, HDL2 and HDL3 in normo- and hyperlipidemic subjects

Total high density lipoprotein (HDL) cholesterol and cholesterol in its main subfractions, HDL2 and HDL3, were determined in 160 normo- and 90 hyperlipidemic subjects by density gradient ultracentrifugation (range of HDL-cholesterol: 0.05-2.85 mmol/l). Both in the normolipidemics and in the combined group HDL3-cholesterol (HDL3-chol) as well as HDL2-cholesterol (HDL2-chol) showed a parabolic relationship with total HDL-chol. The results indicate, that at low total HDL-chol values almost all cholesterol is present in the HDL3 fraction, which shows a linear increase with total HDL-chol from 0 to 0.75 mmol/l. At a further increase of total HDL-chol, cholesterol is increasingly isolated in the HDL2-fraction, especially when HDL3-chol has reached its maximum (about 1.25 mmol/l). Thus, the magnitude of the absolute intra-individual variation of either HDL3-chol or HDL2-chol (in mmol/l) is related to the total HDL-chol concentration. Given the strong correlation between cholesterol in both HDL-subfractions with total HDL-chol and the inverse relationship of total HDL-chol with the risk for coronary heart disease, a rise in HDL3-chol or in HDL2-chol may be equally favorable.     

Predictors of coronary bypass grafting in a population of middle-aged men.

BACKGROUND: Coronary bypass grafting is a procedure which is usually undertaken because of extensive coronary heart disease, whereas acute myocardial infarction may occur with patients with moderate or even minimal disease. Having undergone coronary bypass grafting may thus serve as a marker for extensive coronary atherosclerosis. The aim of this study was to assess risk factors for future coronary bypass grafting as a first coronary event, and to compare them with risk factors for a first acute myocardial infarction. DESIGN: This was a prospective cohort study. METHOD: In the Multifactor Primary Prevention Study, 7388 men aged 47-55 years and free of previous acute myocardial infarction or stroke were investigated between 1970 and 1973. During 28 years of follow-up 1664 men (22%) had an acute myocardial infarction or died from coronary disease. One hundred and forty six men (2%) underwent coronary bypass grafting with no prior acute infarction. RESULTS: Serum cholesterol was a stronger predictor of coronary bypass grafting than of acute myocardial infarction. Compared to men with serum cholesterol of 5.0 or lower, men with serum cholesterol 5.1-6.4, 6.5-7.4 and over 7.4 mmol/l had age-adjusted hazard ratios for acute myocardial infarction of 1.22 (1.00-1.49), 1.66 (1.35-2.03) and 2.04 (1.65-2.51). Corresponding hazard ratios for coronary bypass grafting were 1.57 (0.66-3.70), 3.44 (1.47-8.03) and 5.21 (2.20-12.31) (95% confidence interval). In contrast, smoking was a weaker risk factor for coronary bypass grafting than for acute myocardial infarction with no discernible increase in risk except in very heavy smokers (25 g/day or more; n=193); hazard ratio 2.19 (1.02-4.66). Elevated blood pressure predicted coronary bypass grafting and acute myocardial infarction equally well. In multivariate analysis an increase in serum cholesterol of 1 mmol/l was associated with an odds ratio of 1.56 (1.38-1.76) for coronary bypass grafting but only 1.30 (1.24-1.36) for AMI (P for difference in odds ratio 0.004). CONCLUSION: Elevated serum cholesterol is a stronger predictor for future coronary bypass grafting than for acute myocardial infarction. Moderate smoking was not associated with coronary bypass grafting. Different manifestations of coronary disease have different risk factor patterns, suggesting that secular changes in risk factor pattern could potentially influence the clinical expression of the disease.     

Myocardial infarction in young men. Study of risk factors in nine countries.

In order to determine whether the development of myocardial infarction in different countries is associated with different risk factors, 240 male survivors, aged 40 or less, were studied in nine countries. In the seven centres in developed countries (Auckland, Melbourne, Los Angles/Atlanta, Cape Town, Tel Avic, Heidelberg, and Edinburgh) there was a high procedure of risk factors, particularly of hyperlipidaemia and cigarette smoking. The prevalence of hypertension, obesity, hyperglycaemia, and hyperuricaemia varied from centre to centre. Risk factors were less prevalent in Bombay and Singapore: the most common risks operating in Bombay seemed to be cigarette smoking and hyperglycaemia, while in Singpore cigarette smoking was the commonest. The mean age of the whole group was 35.4 years. Serum cholesterol levels of 7.25 mmol/l (280 mg/dl) or more were present in 25 per cent of all patients, serum triglyceride levels of 2.26 mmol/l )l200 mg/dl) or more in 35 per cent. 80 per cent of the patients were smokers, and 15 per cent were either for hypertension before myocardial infarction or had a raised blood pressure after myocardial infarction. Obesity was found in 19 per cent of all patients and serum uric acid levels over 0.5 mmol/l (8.5 mg/dl) in 17 per cent. 10 per cent of all patients were either treated for diabetes mellitus before myocardial infarction or showed an abnormal glucose tolerance after myocardial infarction. This collaborative study may help, by showing differences in the prevalence of risk factors, to indicate to each centre and to national and to international organizations, the direction for their future studies into the causation and prevention of myocardial infarction in young men.     

Myocardial infarction in young men. Study of risk factors in nine countries.

In order to determine whether the development of myocardial infarction in different countries is associated with different risk factors, 240 male survivors, aged 40 or less, were studied in nine countries. In the seven centres in developed countries (Auckland, Melbourne, Los Angles/Atlanta, Cape Town, Tel Avic, Heidelberg, and Edinburgh) there was a high procedure of risk factors, particularly of hyperlipidaemia and cigarette smoking. The prevalence of hypertension, obesity, hyperglycaemia, and hyperuricaemia varied from centre to centre. Risk factors were less prevalent in Bombay and Singapore: the most common risks operating in Bombay seemed to be cigarette smoking and hyperglycaemia, while in Singpore cigarette smoking was the commonest. The mean age of the whole group was 35.4 years. Serum cholesterol levels of 7.25 mmol/l (280 mg/dl) or more were present in 25 per cent of all patients, serum triglyceride levels of 2.26 mmol/l )l200 mg/dl) or more in 35 per cent. 80 per cent of the patients were smokers, and 15 per cent were either for hypertension before myocardial infarction or had a raised blood pressure after myocardial infarction. Obesity was found in 19 per cent of all patients and serum uric acid levels over 0.5 mmol/l (8.5 mg/dl) in 17 per cent. 10 per cent of all patients were either treated for diabetes mellitus before myocardial infarction or showed an abnormal glucose tolerance after myocardial infarction. This collaborative study may help, by showing differences in the prevalence of risk factors, to indicate to each centre and to national and to international organizations, the direction for their future studies into the causation and prevention of myocardial infarction in young men.     

Are high density lipoprotein (HDL) and triglyceride levels relevant in stroke prevention?

Although statins reduce the risk of non-haemorrhagic strokes and transient ischaemic attacks (TIA), little is known about the efficacy of fibrates. This situation has been partly remedied by the recent publication of two-fibrate based trials--The Veterans Affairs High Density Lipoprotein Cholesterol Intervention Trial (VAHIT) and the Bezafibrate Infarction Prevention Trial (BIP). In BIP, bezafibrate did not significantly reduce the risk of a cerebrovascular event (CVE). Bezafibrate increased the high density lipoprotein cholesterol (HDL) level by 18% to 40 mg/dl (1.03 mmol/l) and decreased triglyceride (TG) levels by 21% to 115 mg/dl (1.29 mmol/l). In contrast, in VAHIT, gemfibrozil significantly reduced the risk of investigators designated stroke (P=0.04) and TIA (P<0.001). Gemfibrozil increased HDL by 6% to 33 mg/dl (0.85 mmol/l) and decreased TG by 31% to 110 mg/dl (1.25 mmol/l). However, the baseline low density lipoprotein cholesterol (LDL) levels were higher in BIP than in VAHIT (148 versus 111 mg/dl; 3.82 versus 2.87 mmol/l). LDL levels were not markedly altered by treatment in either trial. Fibrates can improve several CVE predictors, like fibrinogen, lipoprotein (a), insulin sensitivity and platelet activity. Furthermore, lowered HDL and/or raised TG levels are associated with an increased risk of a CVE; fibrates are an appropriate treatment for this lipid profile. In conclusion, the evidence suggests that not only total cholesterol and LDL, but also HDL and TG levels predict the risk of a CVE. Statins, fibrates or a combination of these drugs can modify these variables.