Coronary Risk Markers Research Articles

Interleukin-6 Correlates with Endothelial Dysfunction in Young Post-Myocardial Infarction Patients

Background: The estimation of coronary risk based on consideration of classical risk factors is insufficient in young patients with myocardial infarction who have low expressions of classical risk factors. Endothelial dysfunction (ED) and markers of vascular inflammation may be more appropriate for risk estimation. The relations among ED and inflammation markers in such patients have not yet been explored. Patients and Methods: Twenty-one patients (on average 44 years old) in the stable phase after myocardial infarction, with low expressions of risk factors, were included in the study. The control group consisted of 25 healthy age-matched males. ED was estimated by ultrasound measurement of the endothelium-dependent dilatation of the brachial artery. The following inflammation markers were measured: hsCRP, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), ICAM-1, VCAM-1, selectin-P and selectin-E. Results: Patients had a significantly reduced level of endothelium-dependent vasodilatation (5.6 ± 3.5 vs. 8.8 ± 6.5%, p < 0.05), and an increased level of IL-6 (3.2 [1.5–8.4] vs. 1.4 [0.9–2.3] ng/ml; p < 0.01). All other inflammation markers were comparable to controls. We found a significant negative correlation between ED and the levels of IL-6 (r = –0.54, p = 0.012). Conclusion: It appears that IL-6 is the most valuable circulating marker of ED, and consequently a useful marker of coronary risk.

Evaluation of a scoring scheme, including proinsulin and the apolipoprotein B/apolipoprotein A1 ratio, for the risk of acute coronary events in middle-aged men: Uppsala Longitudinal Study of Adult Men (ULSAM)

Background In recent years, the importance of circulating levels of proinsulin and apolipoproteins as risk factors for myocardial infarction (MI) has been highlighted. The aims of the current study were to investigate whether introduction of these new markers of coronary risk could improve the performance of a risk prediction score and to compare this new score with traditional scoring schemes, such as the Framingham Study and the Prospective Cardiovascular Munster (PROCAM) Study schemes. Methods From 1970 to 1973 all 50-year-old men in Uppsala, Sweden, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease (the Uppsala Longitudinal Study of Adult Men [ULSAM] cohort). The current study investigated metabolic characteristics at baseline and the incidence of fatal and nonfatal MI (n = 251) during 28.7 years of follow-up in 1108 men who were free of coronary heart disease at baseline. Results The risk prediction score was derived from one half of the population sample from the ULSAM cohort and included systolic blood pressure, smoking, family history of MI, serum proinsulin, and the ratio between apolipoprotein B and apolipoprotein A1.The score was highly predictive for future MI (hazard ratio, 1.77 for a 1 SD increase; 95% CI, 1.49 to 2.10, P < .0001) in the other half of the population that was not used for generating the score. The ULSAM score performed slightly better than the Framingham and PROCAM scores (evaluated as areas under the receiver operating curves; Framingham, 61%; PROCAM, 63%; ULSAM, 66%; P = .08). Conclusions A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was highly predictive for future fatal and nonfatal MI and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors.

Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and incident coronary heart disease: The PRIME Study

The Epidemiological Study of Myocardial Infarction Study which enrolled 9758 apparently healthy men aged 50–59 years, is a prospective cohort study designed to evaluate markers of coronary risk. Soluble forms of the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels were measured in plasma obtained at baseline from 317 subjects who suffered a coronary event during the 5-year follow-up and in twice the number of control subjects who were matched for center, age and day of inclusion in a nested case-control design. The relative risk associated with the highest compared with the lowest thirds of ICAM-1 (>625 versus <502 ng/ml) was 2.45 (95% CI: 1.64–3.65, P<0.001) without adjustment; it decreased moderately (RR: 2.09; 95% CI: 1.34–3.24, P<0.001) after control for lipid and non-lipid factors and remained significantly elevated after adjustment for C-reactive protein (CRP) (RR: 1.90; 95% CI: 1.21–2.96, P=0.005). Plasma ICAM-1 was essentially associated with the risk of myocardial infarction or coronary death and also with angina pectoris. Subjects with CRP presented elevated coronary risk only if ICAM-1 was high. An elevated level of VCAM-1 was not associated with any risk of future acute coronary event, or with angina pectoris. This data indicates that plasma levels of ICAM-1 may serve as risk markers for future coronary events whatever their clinical presentation and that risk is better defined using simultaneous measurements of ICAM-1 and CRP than any of these levels separately.

Usefulness of high-sensitivity C-Reactive protein in predicting long-term risk of death or acute myocardial infarction in patients with unstable or stable angina pectoris or acute myocardial infarction

High-sensitivity C-reactive protein (CRP), proposed as a new coronary risk marker, may reflect either an acute phase reaction or the level of chronic inflammation. Thus, CRP may be less predictive of long-term outcomes when measured after acute myocardial infarction (AMI) than after unstable angina pectoris (UAP) or stable angina pectoris (SAP). A total of 1,360 patients with severe coronary artery disease (≥1 stenosis ≥70%) had CRP levels obtained at angiography. Presenting diagnoses were SAP (n = 599), UAP (n = 442), or AMI (n = 319). During follow-up (mean 2.8 years), death or nonfatal AMI (D/AMI) occurred in 19.5%, 16.1%, and 17.2% (p = NS) with SAP, UAP, and AMI, respectively. Corresponding median CRP levels were 1.31, 1.27, and 2.50 mg/dl (p <0.001). For the overall cohort, increasing age, low ejection fraction, revascularization, and elevated CRP were the strongest of 6 independent predictors for D/AMI. Among those presenting with SAP, CRP levels above the first tertile were associated with an adjusted hazard ratio of 1.8 (95% confidence interval [CI] 1.2 to 2.8, p <0.009) for D/AMI. After UAP, the hazard ratio was 2.7 (95% CI 1.4 to 5.0, p <0.002). However, when measured during hospitalization for AMI, CRP was not predictive of long-term outcome (hazard ratio 1.0 [95 % CI 0.5 to 1.7] p = 0.86). In conclusion, predischarge CRP levels are higher after AMI than after UAP or SAP. However, whereas CRP is strongly predictive of long-term D/AMI for patients presenting with SAP or UAP, it is not predictive shortly after AMI, suggesting that measurements should be delayed until the acute phase reaction is over and levels have returned to baseline.

The Influence of Exercise and Estrogen Replacement on Primary Lipid Coronary Risk Markers in Postmenopausal Women

Although endurance exercise and supplemental estrogen have both been shown to improve serum lipid cardiac risk profiles in postmenopausal women, data regarding a possible synergistic influence are scarce and inconsistent. The purpose of this study was to determine whether such a synergistic influence could be demonstrated. Serum concentrations of total cholesterol (TC), HDL-cholesterol (HDL-C), HDL2-C, HDL3-C, LDL-C, and triglycerides (TG) were obtained from postmenopausal women (N = 45) in each of 4 groups: currently exercising and taking estrogen replacement, exercising and not taking estrogen, sedentary and taking estrogen, and sedentary and not taking estrogen. HDL-C was on average 21% higher (p &lt; .05) and the HDL-C:LDL-C ratio on average 45% higher (p &lt; .05) in the exercise-plus-estrogen group than in any of the other 3 groups. It was concluded that the combination of endurance exercise and estrogen replacement might be associated with better lipid coronary risk profiles in postmenopausal women than either intervention alone.

Haemochromatosis gene mutations and risk of coronary artery disease.

The identification of mutations in the haemochromatosis gene (HFE) (C282Y and H63D) provides the unique opportunity to test whether genetic variants that are associated with tissue iron accumulation may influence the risk of coronary atherosclerosis. To this aim the prevalence of C282Y and H63D mutations was determined in 174 patients with angiographically documented CAD (>50% stenosis) and history of MI, 187 healthy free-living individuals and 142 blood donors. C282Y and H63D mutations were not found to be more frequent in coronary patients as compared to controls. Moreover, these HFE variants were unrelated to the severity of coronary atherosclerosis. These findings did not provide evidence of an association between HFE mutations and the presence of coronary atherosclerosis or its major ischaemic complications, thus indicating that HFE mutations are poor genetic markers of coronary risk.

Fibrinogen and coronary risk.

The notion that fibrinogen is strongly, consistently, and independently related to coronary risk has been widely accepted. The evidence is based on numerous prospective epidemiological studies and clinical observations. However, the reasons why fibrinogen is elevated in coronary disease and in atherosclerosis are only incompletely understood. All cells involved in the atherogenetic process are able to produce cytokines which induce an acute phase reaction. The potential pathophysiologic mechanisms by which elevated fibrinogen levels mediate coronary risk are manifold: It forms the substrate for thrombin and represents the final step in the coagulation cascade; it is essential for platelet aggregation; it modulates endothelial function; it promotes smooth muscle cell proliferation and migration; it interacts with the binding of plasminogen with its receptor; and finally it represents a major acute phase protein. Whether or not fibrinogen is causally involved in atherothrombogenesis still remains to be determined, and even though other unsolved issues await conclusive answers, fibrinogen has emerged as an important additional marker of coronary risk.

Which haemostatic factors should be measured in clinical practice for the prediction of coronary risk?

The study of plasmatic factors of the haemostatic system has provided further insight into the pathophysiology of occlusive arterial vessel diseases. Additionally, they may contribute to clinical strategies of risk prediction in an individual patient. It has turned out that not only an increased risk of suffering first or new coronary events may be predicted, but also the chance of low probability. Elevated levels of fibrinogen, von Willebrand-factor antigen, factor VIIc, tPA-antigen and low PAI-1 concentrations — included into a coronary risk score — may add markedly to the predictive power of the other known coronary risk markers. Low fibrinogen and low tPA-antigen indicate low coronary risk, particularly, if at the same time CRP is low. This remains true even it total- or LDL-cholesterol is high. The mechanism of how low fibrinogen protects against the deleterious effects of high plasma lipid levels remains unknown so far. Thus, the described improvement of individual prediction of increased or low coronary risk will, on the one hand, aid the doctor to tranquilize anxious patients and to minimize preventive measures. On the other hand, doctor and patient are motivated to intensify these in patients at increased risk.

Chronobiology of Coronary Risk Markers in Greenland Eskimos: A Comparative Study with Caucasians Residing in the Same Arctic Area

We report a comparison of fibrinolytic variables between 10 Caucasians on a predominantly European diet and 10 Greenland Eskimos on a traditional Inuit diet containing a substantial amount of fish and sea animals. We studied the diurnal variation in tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) antigens and activities during a 24-h period. Blood samples were taken every 4 h. The variations of the sinusoidal curves were evaluated by the Friedman chi 2 test. t-PA and PAI-1 antigen in plasma fluctuated significantly during the 24 h (Eskimos p less than 0.00007 and p less than 0.0007; Caucasians p less than 0.00003 and p less than 0.02), with a peak in the early morning and a nadir in the afternoon. This also held true for PAI activity (Eskimos p less than 0.0008; Caucasians p less than 0.01), whereas t-PA activity showed an inverse but still significant pattern (Eskimos p less than 0.006; Caucasians p less than 0.0008). Amplitudes, areas underneath, and overall medians of the sinusoidal curves did not deviate between the two groups with respect to t-PA and PAI. In contrast to the significant variation of t-PA and PAI, the plasma concentrations of fibrin degradation products (D-Dimer), a measure of effective fibrinolysis, remained constant during the 24 h, and the absolute differences between groups did not reach statistical significance. These findings suggest that circadian variation of fibrinolytic activators and inhibitors is a basic biologic phenomenon, which is not affected by life-style, dietary habits, or ethnic differences.(ABSTRACT TRUNCATED AT 250 WORDS)