Incidence Of Acute Coronary Events Research Articles

Lipid lowering reduces proteolytic and prothrombotic potential in rabbit atheroma.

Thrombus formation at sites of atheromatous plaque disruption cause most acute coronary events such as myocardial infarction and unstable angina. Lesional macrophages and smooth muscle cells produce matrix metallo-proteinases (MMPs) and tissue factor (TF), the molecules likely contribute to plaque rupture and thrombus formation. Recent clinical studies have suggested that lipid lowering can reduce the incidence of acute coronary events. We have recently determined the effects of long-term dietary lipid lowering on atheroma of high-cholesterol-fed rabbits. Lipid lowering diminished macrophage accumulation, reduced expression and activity of MMPs, and increased interstitial collagen accumulation in rabbit atheroma. Expression and activity of TF in atheroma also substantially decreased during lipid lowering. Dietary lipid lowering also promoted accumulation of mature smooth muscle cells expressing less MMPs and TF in the plaque's fibrous cap. These results suggest potential mechanisms by which lipid lowering reduces acute coronary events in patients by decreasing proteolytic and prothrombotic activity within the atheroma.

Hyperinsulinemia and the risk of cardiovascular death and acute coronary and cerebrovascular events in men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

The role of hyperinsulinemia as a cardiovascular risk factor is controversial. We studied whether hyperinsulinemia is independently associated with increased cardiovascular morbidity and mortality. Fasting serum insulin level and other cardiovascular risk factors were determined in 1521 men in eastern Finland aged 42 to 60 years with neither cardiovascular disease nor diabetes at baseline. Forty-five cardiovascular deaths, 110 acute coronary events, 48 strokes, and 163 any cardiovascular events occurred during an average follow-up of 9.5 years. A total of 163 cardiovascular events (45 cardiovascular deaths, 110 acute coronary events, and 48 strokes) occurred during an average follow-up of 9.5 years. In Cox regression analysis adjusting for age and examination years, fasting serum insulin level as a continuous variable was directly associated with the risk of cardiovascular death (P = .006), acute coronary events (P = .04), and stroke (P = .02). Men with insulin levels of 52 to 66 pmol/L, 67 to 89 pmol/L, and 90 pmol/L or more (3 highest quartiles) had 1.4-fold (95% confidence interval, 0.5-3.7), 1.4-fold (95% confidence interval, 0.5-3.7), and 2.5-fold (95% confidence interval, 1.0-5.9; P = .05) cardiovascular mortality, respectively, compared with men with insulin levels of less than 52 pmol/L (lowest quartile) (P = .04 for linear trend). Adjustment for serum lipid levels, blood pressure, and obesity reduced the excess cardiovascular mortality in the highest insulin quartile by 7%, 33%, and 67%, respectively. There were no statistically significant differences in the incidence of acute coronary events and stroke between the insulin quartiles. Hyperinsulinemia had a modest association with increased cardiovascular mortality in middle-aged men. This relationship was largely explained by obesity, hypertension, and dyslipidemia. Hyperinsulinemia had even weaker associations with the risk of acute coronary event and stroke.

Clinical significance of increased plasma concentration of macrophage colony–stimulating factor in patients with angina pectoris

OBJECTIVESTo determine the effect of macrophage colony–stimulating factor (MCSF) on atherogenesis in patients with coronary artery disease (CAD), we assessed the relation between the plasma concentration of MCSF and the incidence of acute coronary events in patients with CAD.BACKGROUNDCytokines such as MCSF play a central role in inflammatory and proliferative responses in patients with acute coronary syndromes. However, the effect of MCSF on the clinical course in patients with CAD is still not known.METHODSWe measured the plasma MCSF concentration in 142 patients with documented CAD (62 ± 9 years) and followed up for a mean period of 14 ± 6 months. The study included 97 patients with stable angina (SA), 45 patients with unstable angina (UA) and 22 age-matched control subjects. The predictors of coronary events were analyzed by using a Cox proportional hazards model.RESULTSThe mean plasma MCSF concentration in patients with UA was significantly higher than that in patients with SA and in control subjects (981 ± 277 vs. 693 ± 223 vs. 680 ± 158 pg/ml, p < 0.001). The mean plasma MCSF concentration in the 20 patients with coronary events was significantly higher than that in patients without coronary events (1,192 ± 232 vs. 690 ± 213 pg/ml, p < 0.001). The predictors of unfavorable outcome were an increased MCSF concentration, the presence of CAD and a low ejection fraction.CONCLUSIONSThese findings suggest that an increased circulating MCSF concentration reflects atherosclerotic progression in patients with CAD and predicts future cardiac events.

Increased platelet reactivity to the aggregatory effect of platelet activating factor, in vitro, in patients with heterozygous familial hypercholesterolaemia

Patients with familial hypercholesterolacmia (FH) present with high plasma total- and low density lipoprotein (LDL)-cholesterol levels and develop premature and often severe atherosclerosis. Elevations of total- and LDL-cholesterol levels are not only related to an increased risk of atherosclerosis, but may also exert prothrombotic effects via platelet activation leading to acute coronary events. In the present work, the platelet response to the aggregatory effect of platelet-activating factor (PAF) in relation to the plasma PAF-acetylhydrolase (PAF-AH) activity and to their lipidaemic profile was studied in 20 heterozygous FH patients. The PAF EC50 aggregation values in the patient group were significantly decreased (P < 0.03) compared with the control group (19.5 ± 5.2 nM and 30.4 ± 7.2 nM, respectively). Moreover, the maximal percentage of aggregation to 100 nM PAF was significantly increased in the patient group compared with controls (26.5 ± 8.2% vs 15.2 ± 3.1%, respectively, P < 0.03). Both platelet aggregation parameters were correlated to the plasma total- and LDL-cholesterol levels, as well as to the apolipoprotein B (apo B) levels. The maximal percentage of aggregation to 10 μM ADP was also significantly increased in the patient group compared with controls (51.5 ± 10.3% vs 32.4 ± 9.0%, respectively, P < 0.02) but was not correlated to any plasma lipid parameter. The total plasma PAF-AH activity in the heterozygous FH patients was significantly higher compared with controls (109.8 ± 15.9 nmol/ml per min vs 68.4 ± 18.0 nmol/ml per min, respectively, P < O.OOOl), whereas the HDL-associated PAF-AH activity did not differ significantly between the two groups. Our results suggest that the increased aggregatory response of platelets to PAF despite the significantly higher plasma PAF-AH activity, could be an important factor contributing to the higher atherogenicity and incidence of acute coronary events observed in patients with heterozygous FH.

Increased platelet reactivity to the aggregatory effect of platelet activating factor, in vitro, in patients with heterozygous familial hypercholesterolaemia

Patients with familial hypercholesterolaemia (FH) present with high plasma total- and low density lipoprotein (LDL)-cholesterol levels and develop premature and often severe atherosclerosis. Elevations of total- and LDL cholesterol levels are not only related to an increased risk of atherosclerosis, but may also exert prothrombotic effects via platelet activation leading to acute coronary events. In the present work, the platelet response to the aggregatory effect of platelet-activating factor (PAF) in relation to the plasma PAF-acetylhydrolase (PAF-AH) activity and to their lipidemic profile was studied in 20 heterozygous FH patients. The PAF EC(50) aggregation values in the patient group were significantly decreased ( P < 0.03) compared with the control group (19.5 5.2 nM and 30.4 7.2 nM, respectively). Moreover, the maximal percentage of aggregation to 100 nM PAF was significantly increased in the patient group compared with controls (26.5 8.2% vs 15.2 3.1%, respectively, P < 0.03). Both platelet aggregation parameters were correlated to the plasma total- and LDL-cholesterol levels, as well as to the apolipoprotein B (apo B) levels. The maximal percentage of aggregation to 10 microM ADP was also significantly increased in the patient group compared with controls (51.5 10.3% vs 32.4 9.0%, respectively, P < 0.02) but was not correlated to any plasma lipid parameter. The total plasma PAF-AH activity in the heterozygous FH patients was significantly higher compared with controls (109.8 15.9 nmol/ml per min vs 68.4 18.0 nmol/ml per min, respectively, P < 0.0001), whereas the HDL-associated PAF-AH activity did not differ significantly between the two groups. Our results suggest that the increased aggregatory response of platelets to PAF despite the significantly higher plasma PAF-AH activity, could be an important factor contributing to the higher atherogenicity and incidence of acute coronary events observed in patients with heterozygous FH.

Link between intracellular pathogens and cardiovascular diseases

Atherosclerosis is a multifactorial disease with an important inflammatory component. Inflammatory cells such as T-lymphocytes, macrophages and monocytes play a key role not only in its origin but also during plaque rupture. In addition, it has been suggested that infection could be the cause of atherosclerosis. Serologic studies involving polymerase chain reaction, immunocytochemistry and electron microscopy support the hypothesis of an association between Chlamydia pneumoniae and atherosclerosis. This intracellular pathogen is able to replicate in macrophages, vascular cells and smooth muscle cells. C. pneumoniae can then release inflammatory cytokines which contribute to instability of the plaque. C. pneumoniae may be recovered through cell culture from coronary atherosclerotic plaques and has a strong association with one allele, of the major histocompatibility system among patients with acute coronary syndromes. Other intracellular pathogens that have been implicated in atherosclerosis include cytomegalovirus, Mycoplasma pneumoniae and Helicobacter pylori. To test the hypothesis that C. pneumoniae plays a role in the instability of plaque, we conducted a prospective clinical trial, using the macrolide antibiotic roxithromycin in 202 patients. The preliminary results show a statistically significant reduction in the incidence of acute coronary events at 30 days.

The self-employed and the self-driven: two coronary-prone subpopulations from the Zeist study.

In four Dutch communities, Zeist, De Bilt, Driebergen, and Doorn (total population, 111,000 inhabitants), all patients who suffered acute coronary events between July 1970 and March 1974 were recorded. By combining data from this study with data from the 1971 national census of the Netherlands, it was possible to demonstrate that the incidence of acute coronary events is twice as high for self-employed men as for employed men and as much as seven times as high for self-employed women as for housewives. The incidence of acute coronary events is practically the same for self-employed women aged 45-69 years as for men of the same age in the general population. Men aged 35-64 years whose nature is such that they feel driven to do all their work with great intensity and against the clock ("self-driven men") suffer myocardial infarction seven times as frequently as others and are 2.4 times as likely to die of fatal coronary attack. Only 10% of the self-employed male referents, but 50% of the self-employed male cases, consider themselves self-driven. On the other hand, experiences of excessive working hours and time pressures are not related to the incidence of acute coronary events. These results were not influenced by and were independent of other known risk indicators.

Walking, cycling, or gardening, with or without seasonal interruption, in relation to acute coronary events.

The case-referent study reported here investigates the relationship between acute coronary events (ACE) and sustained light physical exercise, mainly leisure-time walking, cycling, or gardening (WCG). These activities are classified as habitual WCG (greater than 8 months/year), seasonal WCG (4--8 months), or occasional WCG (less than 4 months), each category being further subdivided according to the number of hours a week: less than 4 hours, 4--7 hours, or greater than 7 hours. A significant negative association is found between ACE and habitual WCG. No such relationship is evident between ACE and seasonal WCG, however, seasonal WCG being equally frequent (27%) in both cases and referents. These observations may indicate that any effect on the incidence of acute coronary events that is caused by walking, cycling, or gardening is neutralized if these activities are interrupted for several months of the year. The negative association between habitual WCG and ACE does not depend on the number of hours a week devoted to SCG and is not enhanced by more vigorous additional exercise. The fatality of ACE (death rate within 4 weeks) is significantly higher in the least active group (WCG less than 4 months/year).