Risk Of Future Coronary Artery Disease Research Articles

Role of Nonenhanced Multidetector CT Coronary Artery Calcium Testing in Asymptomatic and Symptomatic Individuals

Arteriosclerotic cardiovascular disease is the leading cause of death in the United States, with coronary artery disease (CAD) accounting for half of all cardiovascular disease deaths. Current risk assessment approaches for coronary heart disease, such as the Framingham risk score, substantially misclassify intermediate- to long-term risk for the occurrence of CAD in asymptomatic individuals. A screening modality such as a simple non-contrast-enhanced, or noncontrast, computed tomographic (CT) detection of coronary artery calcium (CAC) improves the ability to accurately predict risk in vulnerable groups and adds information above and beyond global risk assessment as shown by the recent Multi-Ethnic Study of Atherosclerosis. In addition, absence of CAC is associated with a very low risk of future CAD and as a result can be used to identify a group among which further testing and pharmacotherapies can be avoided. The Expert Consensus Document by the American College of Cardiology Foundation and the American Heart Association now recommends screening individuals at intermediate risk but did not find enough evidence to recommend CAC testing and further stratification of those in the low- or high-risk categories for CAD. In addition, emerging guidelines have suggested that absence of CAC can act as a "gatekeeper" for further testing among low- and intermediate-risk patients presenting with chest pain. This review of the current literature outlines the role of CAC testing in both asymptomatic and symptomatic individuals.

Serum Total Bilirubin Concentration Is Inversely Correlated with Framingham Risk Score in Koreans

Compelling evidence suggests that bilirubin, via its antioxidant potential, has anti-atherogenic properties, and that serum bilirubin concentrations within the reference range for the general population may provide some protection against coronary artery disease (CAD). This study examined the association between serum total bilirubin concentration and Framingham risk score (FRS) in the Korean population. This cross-sectional study was performed on 19,792 Koreans. In addition to FRS, data on body mass index, fasting blood glucose, liver enzymes, lipid profile, uric acid, gamma glutamyltransferase, high-sensitive C-reactive protein and total bilirubin were used. Negative correlations were established between log-transformed total bilirubin concentration and FRS (females; r = -0.067, p <0.001, males; r = -0.128, p <0.001). Analyses relating total bilirubin to FRS ≥10% utilized multiple confounder adjusted logistic regression. Unadjusted odd ratios for FRS ≥10% were 0.325 (95% CI: 0.160-0.659, p = 0.002) and 0.342 (95% CI: 0.281-0.417, p <0.001) for log-transformed total bilirubin in females and males, respectively. These inverse relationships remained significant after adjustments for multiple confounders in both genders. Increased total bilirubin concentrations are associated with the decrease in FRS. Serum total bilirubin may be helpful to decrease the future risk of CAD.

Telomerase, telomere length, and coronary artery calcium in black and white men in the CARDIA study

Objective To evaluate whether telomerase activity, measured in circulating blood leukocytes, might be associated with prevalent atherosclerosis, or predict future coronary artery disease risk. Methods and results We examined associations of telomerase activity levels measured at year 15 in the Coronary Artery Risk Development in Young Adults (CARDIA) Study with prevalent coronary artery calcium (CAC), progressive CAC at year 20, and incident CAC between years 15 and 20, in 440 black and white men aged 33–45 years. Telomere length was also measured in a subset of participants ( N = 129). In multivariate-adjusted analysis, higher quartiles of telomerase were cross-sectionally associated with greater odds of prevalent CAC at year 15 (quartile 2: OR = 1.32, 95% CI: 0.54–3.23; quartile 3: OR = 1.40, 95% CI: 0.60–3.30; quartile 4: OR = 3.27, 95% CI: 1.39–7.71 compared with quartile 1, p-continuous = 0.012) and progressive CAC at year 20, but telomerase was not significantly associated with incidence of newly detectable CAC. Higher telomerase activity levels predicted greater CAC progression at year 20 among persons with short telomere length; low telomerase and short TL predicted less CAC progression. Conclusion Telomerase activity in leukocytes was associated with calcified atherosclerotic plaque, and was also a predictor of advancing plaque among persons with short telomeres.

Silent myocardial ischaemia and long-term coronary artery disease outcomes in apparently healthy people from families with early-onset ischaemic heart disease

A family history of premature coronary artery disease (CAD) in an apparently healthy individual conveys an increased risk of future CAD. The extent to which inducible myocardial ischaemia exists and is associated with long-term incident CAD in apparently healthy siblings of early-onset CAD patients is unknown. Asymptomatic siblings (n = 1287, aged 30-59 years) of patients with onset of CAD <60 years of age underwent risk factor screening and maximal graded treadmill testing with nuclear perfusion imaging, and were followed for incident CAD events for up to 25 years. Incident CAD occurred in 15.2% of siblings (68% acute coronary syndromes); mean time to first CAD event was 8.2 ± 5.2 years. Inducible ischaemia was highly prevalent in male siblings (26.9%), and was independently associated with incident CAD. Male siblings ≥ 40 years of age who were low or intermediate risk by traditional risk assessment, had a prevalence of inducible ischaemia and a 10-year risk of incident CAD that were near or ≥ 20%. In female siblings ≥ 40 years of age, the presence of inducible ischaemia was also independently associated with incident CAD, but the prevalence of inducible ischaemia was markedly lower, as was the risk of incident CAD. Inducible ischaemia is highly prevalent in male siblings, suggesting a previously unknown long quiescent period before the occurrence of a clinical event. While inducible ischaemia is associated with a worse prognosis, male siblings with negative tests still bear a high risk of incident disease, such that we propose that in male siblings over 40 years of age, aggressive primary prevention interventions be instituted without nuclear testing. For women, the prevalence of ischaemia was so low as to not warrant screening, but the incidence of CAD was high enough to at least warrant lifestyle interventions.

Serum Gamma-Glutamyltransferase Concentration Correlates with Framingham Risk Score in Koreans

Gamma-glutamyltransferase (GGT) is a novel coronary artery disease (CAD) risk factor, but its use as an independent factor for CAD risk prediction remains unclear in Asian population. This study examined the association between serum GGT concentration and Framingham risk score (FRS) in the Korean population. This cross-sectional study was performed on 30,710 Koreans. Besides FRS, body mass index, fasting blood glucose, liver enzymes, lipid profile, uric acid and high sensitive C-reactive protein data were used. The study subjects were grouped into quartiles according to the levels of GGT. Analyses relating GGT to FRS ≥ 20% utilized multiple confounders adjusted logistic regression. Positive correlations were established between log-transformed GGT concentration and FRS (r = 0.38; P < 0.001). Increasing the quartile of serum GGT concentration was significantly associated with linear increasing trends in FRS (P-trend < 0.001). Compared to the lowest baseline GGT category, age-gender adjusted odd ratios for FRS ≥ 20% were significantly increased from the lowest to highest GGT quartiles; these results remained significantly after adjustments for multiple confounders. Increased GGT concentration is associated with the increase in FRS. Serum GGT may be helpful to predict the future risk of CAD.

Study on Correlations Between Glycated Haemoglobin, Lipid Profiles and Blood Glucose Levels in Type 2 Diabetics Living at Moderate High Altitude

Introduction: The study was conducted to look for the effects of polycythaemia on Glycosylated Haemoglobin (GHb) levels and to the see the correlations between the levels of haemoglobin, GHb, blood glucose, and lipid profiles including Atherogenic Index of plasma (AIP), in type 2 diabetics living 5800ft above sea level at Gangtok in Sikkim, India. GHb is used to predict the risk of long term complications of Diabetes mellitus (DM) like coronary artery disease (CAD). Materials and Methods: The study group consisted of Group I (Type 2 DM male patients with PPG levels 200mg/ dl) and age matched healthy males formed the control group. Results: In Group I, GHb levels correlated positively with AIP, but not with TC/HDL-C ratio. In Group II, both PPG and GHb levels correlated positively with Total cholesterol (TC), LDL Cholesterol, TC /HDL-C ratio and AIP. This shows that higher PPG levels are associated with more Atherogenic lipid profiles. Study also showed higher GHb levels in controls at 7.61%, and correlated positively with postprandial glucose (PPG) levels (r = 0.92). Conclusion: In predicting risk for future CAD, PPG levels and AIP can be used as an adjunct parameter.

Chemokine Ligand 2 Genetic Variants, Serum Monocyte Chemoattractant Protein-1 Levels, and the Risk of Coronary Artery Disease

In humans, evidence about the association between levels of monocyte chemoattractant protein-1 (MCP-1), its coding gene chemokine (C-C motif) ligand 2 (CCL2), and risk of coronary artery disease (CAD) is contradictory. We performed a nested case-control study in the prospective EPIC-Norfolk cohort investigating the relationship between CCL2 single-nucleotide polymorphisms (SNPs), MCP-1 concentrations, and the risk of future CAD. Cases (n=1138) were apparently healthy men and women aged 45 to 79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n=2237) were matched by age, sex, and enrollment time. Using linear regression analysis no association between CCL2 SNPs and MCP-1 serum concentrations became apparent, nor did we find a significant association between MCP-1 serum levels and risk of future CAD. Finally, Cox regression analysis showed no significant association between CCL2 SNPs and the future CAD risk. In addition, we did not find any robust associations between the CCL2 haplotypes and MCP-1 serum concentration or future CAD risk. Our data do not support previous publications indicating that MCP-1 is involved in the pathogenesis of CAD.

Plasma levels of lecithin:cholesterol acyltransferase and risk offuture coronary artery disease in apparently healthy men and women: aprospective case-control analysis nested in the EPIC-Norfolk populationstudy

LCAT plays a key role in the maturation of HDL, as evidenced by low HDL-cholesterol levels in carriers of deleterious mutations in LCAT. However, the role of LCAT in atherosclerosis is unclear. We set out to study this in a prospective study. Plasma LCAT levels, which strongly correlate with LCAT activity, were measured in baseline nonfasting samples of 933 apparently healthy men and women who developed coronary artery disease (CAD) and 1,852 matched controls who remained free of CAD during 6 year follow-up. LCAT levels did not differ between cases and controls but were higher in women than men. Stratification into LCAT quartiles revealed a positive association with plasma LDL-cholesterol and triglyceride levels in the unexpected absence of an association with HDL-cholesterol. In mixed-gender analyses, the odds ratio (OR) for future CAD in the highest LCAT quartile versus the lowest was 1.00 [confidence interval (CI): 0.76-1.29, P for linearity = 0.902], although opposite trends were observed in men and women. In fact, high LCAT levels were associated with an increased CAD risk in women (unadjusted OR 1.45, CI: 0.94-2.22, P for linearity = 0.036). In contrast to our studies in carriers of LCAT mutations, the current data show that low LCAT plasma levels are not associated with increased atherosclerosis in the general population.

Osteoprotegerin and Soluble Receptor Activator of Nuclear Factor-κB Ligand and Risk for Coronary Events

The purpose of this study was to examine the association between serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) and future coronary artery disease (CAD) in apparently healthy individuals. The identification of OPG as a novel cardiovascular risk marker suggests an association between mediators of bone homeostasis and cardiovascular disease. Serum levels of OPG and RANKL were analyzed in a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study, a cohort study of 25 663 men and women, where 951 apparently healthy individuals who developed a coronary event during 6 years' follow-up were matched by sex and age with 1705 healthy controls. Baseline OPG, but not RANKL, was higher in cases than in controls, and OPG was higher in women than in men. Both men and women in the highest OPG quartile had a higher risk for future CAD. These associations were independent of established cardiovascular risk factors, and when using OPG as a continuous variable, also after adjustment for CRP. In contrast, RANKL showed no association with coronary events. OPG is associated with the risk of future CAD in apparently healthy men and women, independent of established cardiovascular risk factors.

Abstract 3132: Paraoxonase-1 Activity Is not Independently Related with the Risk of Future Coronary Artery Disease

Background Paraoxonase-1 (PON1) is a potent antioxidant enzyme bound to high-density lipoprotein (HDL). Its activity, but not its concentration, is controlled by the PON1 Q192R polymorphism. PON1 is considered to protect against atherogenesis, but it is unclear whether this relation is independent of its carrier, HDL. Objective To evaluate the predictive value of PON1 for coronary artery disease (CAD) we assessed PON1 activity and genotype (Q192R polymorphism) in a large cohort. Methods and results We performed a case-control study nested in the prospective EPIC-Norfolk cohort. Cases (n = 1138) were apparently healthy men and women aged 45–79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n=2237) were matched by age and sex. Serum PON1 activity was lower in cases vs. controls (59.9 ± 44.6 U/L vs. 63.4 ± 46.7 U/L, p=0.020) and correlated with HDL cholesterol (r= 0.16, p&lt;0.0001). Whereas the PON1 Q192R polymorphism strongly controlled PON1 activity (QQ: 27 ± 9, QR: 87 ± 27 and RR 152 ± 44 U/L), it was not related to the risk of future CAD (Odds Ratio [OR] per R allele 0.98 [0.84–1.15], p=0.84). Using conditional logistic regression, quartiles of PON1 activity showed a modest inverse relation with CAD risk (OR for the highest vs. the lowest quartile 0.77 [0.63– 0.95], p=0.013; p for trend over quartiles 0.064). PON1 activity adjusted for Q192R genotype - a proxy for PON1 concentration -correlated better with HDL cholesterol (r=0.29, p&lt;0.0001) and strongly predicted CAD risk (OR for the highest versus the lowest quartile 0.72 (0.58 – 0.91), p for trend over quartiles = 0.005). However, this relation was abolished after adjustment for HDL related parameters (HDL particle number, HDL cholesterol, HDL size and apolipoprotein A-I; OR for highest vs. lowest quartile 0.87 [0.66 –1.16], p for trend over quartiles = 0.13). Conclusion In the largest prospective study to date, we show that PON1 activity inversely relates to CAD risk, but not independently of HDL, presumably due to its close association with the HDL particle. Since the Q192R polymorphism profoundly affects lifelong PON1 activity, our inability to demonstrate a relation between the Q192R polymorphism and CAD risk suggests that PON1 activity is not a causal factor in atherogenesis.

Medical Management of the Diabetic Patient with Coronary Artery Disease

The prevalence of type 2 diabetes is rising at an alarming rate worldwide. Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the diabetic population. Future CAD risk should be routinely assessed in patients with diabetes as specific subgroups might benefit from information derived from cardiac stress testing and other diagnostic procedures. Risk factor control is of paramount importance in all cases and it usually requires sustained lifestyle modifications, coupled with pharmacological interventions. Statins and angiotensin-converting enzyme (ACE) inhibitors are the first-line agents for the treatment of dyslipidaemia and hypertension, respectively. Microvascular, but not macrovascular, complications of diabetes are effectively prevented by good glycaemic control. Metformin is considered the first-choice agent in overweight diabetic subjects, while the role of thiazolidinediones is currently the focus of medical research. The diagnosis of acute coronary events in patients with diabetes is often challenging because of the high prevalence of silent ischaemia in these subjects. All acute cardiac events need to be promptly treated and myocardial reperfusion attempted without delay. Maintaining glucose levels as close to normal as possible, during and shortly after an acute event, improves prognosis in patients with diabetes. Risk factor control remains the cornerstone of secondary prevention; beta-blockers, ACE-inhibitors and antiplatelet agents confer additional symptomatic and survival benefit. Similar therapeutic principles also apply to patients with type 1 diabetes. This article addresses the complex problem of managing patients with diabetes and coronary artery disease.

Can dysfunctional HDL explain high coronary artery disease risk in South Asians?

Background Coronary artery disease (CAD) is the leading cause of mortality and morbidity in United States, and South Asian immigrants (SAIs) have a higher risk for CAD compare to Caucasians. Traditional risk factors do not completely explain high risk, and some of the unknown risk factors need to be explored. We assessed dysfunctional pro-inflammatory high density lipoprotein (HDL) in SAIs and assessed its association with sub-clinical CAD using carotid intima-media thickness (IMT) as a surrogate marker for atherosclerosis. Methods Cross-sectional study on SAIs aged 40–65 years. Sub-clinical CAD was measured using carotid intima media thickness (IMT) as a surrogate marker of atherosclerosis. Dysfunctional or pro-inflammatory HDL was determined by novel cell free assay and HDL inflammatory Index. Results Dysfunctional HDL was found in the 50% participants, with HDL-inflammatory index of ≥ 1.00, suggesting pro-inflammatory HDL (95% CI, 0.8772–1.4333). The prevalence of sub-clinical CAD using carotid IMT (≥ 0.80 mm) was seen in 41.4% (95% CI, 0.2347–0.5933). On logistic regression analysis, positive carotid IMT was found to be associated with dysfunctional HDL after adjusting for age, family history of cardiovascular disease, and hypertension ( p = 0.030). Conclusions The measurement of HDL level as well as functionality plays an important role in CAD risk assessment. Those SAIs with dysfunctional HDL and without known CAD can be a high risk group requiring treatment with lipid lowering drugs to reduce future risk of CAD. Further large studies are required to explore association of dysfunctional HDL with CAD and identify additional CAD risk caused by dysfunctional HDL.

Cord Blood Lipid Profile in a Population of Iranian Term Newborns

Premature coronary artery disease (CAD) and its risk factors are highly prevalent in Iran. It is well documented that atherosclerosis starts in childhood and there is evidence that this association with adult levels may originate at birth, so assessment of serum lipid levels in neonates might be of importance. In this study we aimed to measure serum lipoprotein and apolipoprotein levels in a representative sample of Iranian newborns. Cord blood lipid profile, apolipoprotein A, apolipoprotein B, and lipoprotein a (LPa) were analyzed in 378 full-term, Iranian newborns. The mean values of total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A, apolipoprotein B, and Lpa in girls were 81.4 +/- 28.3, 35.9 +/- 22.4, 31.1 +/- 9.9, 87.9 +/- 20.2, 34.2 +/- 18.2, and 21.0 +/- 2.8 mg/dL, respectively; these values in boys were 75.2 +/- 21.1, 32.1 +/- 16.3, 28.8 +/- 8.7, 84.3 +/- 16.0, 32.6 +/- 14.2, and 19.5 +/- 2.7 mg/dL, respectively. Median values of triglycerides (TGs) in boys and girls were 61 and 62 mg/dL, respectively. Female neonates had significantly higher concentrations of TC and HDL-C than males (81.4 +/- 28.3 vs. 75.2 +/- 21.1, p = 0.02, and 31.18 +/- 9.97 vs. 28.8 +/- 8.7, p = 0.02, respectively). Other biochemical factors were not significantly different between genders. The mean and median concentrations of LPa were 20.3 and 18.7 mg/dL, respectively, which are almost five times higher than those reported in some other studies. The TG concentration was 1.5-2 times higher than those previously reported. Our findings indicate that serum concentrations of LPa and TG in Iranian neonates are higher than those in previous studies; this disorder, which is likely placing Iranians at increased risk for future CADs, needs to be assessed in longitudinal studies.

Apolipoprotein A-II Is Inversely Associated With Risk of Future Coronary Artery Disease

Although the vasculoprotective effects of apolipoprotein A-I (apoA-I), the major protein associated with high-density lipoprotein, have been universally accepted, apoA-II has been suggested to have poor antiatherogenic or even proatherogenic properties. To study this suggestion more closely, we evaluated how serum levels of apoA-II and apoA-I relate to the risk of future coronary artery disease (CAD) in a large, prospective study. We performed a nested case-control study in the prospective EPIC-Norfolk (European Prospective Investigation into Cancer and Nutrition-Norfolk) cohort. Case subjects (n=912) were apparently healthy men and women aged 45 to 79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Control subjects (n=1635) were matched by age, gender, and enrollment time. Conditional logistic regression was used to quantify the relationship between serum apoA-II levels and risk of CAD. Serum apoA-II concentration was significantly lower in case subjects (34.5+/-6.3 mg/dL) than in control subjects (35.2+/-5.8 mg/dL) and was inversely associated with risk of CAD, such that patients in the upper quartile (>38.1 mg/dL) had an odds ratio of 0.59 (95% confidence interval 0.46 to 0.76) versus those in the lowest quartile (<31.1 mg/dL; P for linearity <0.0001). After adjustment for fasting time, alcohol use, and cardiovascular risk factors (systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, body mass index, smoking, diabetes mellitus, and C-reactive protein), the corresponding risk estimate was 0.48 (95% confidence interval 0.34 to 0.67, P for linearity <0.0001). Surprisingly, additional adjustment for serum apoA-I levels did not affect risk prediction of apoA-II for future CAD (odds ratio 0.49, 95% confidence interval 0.34 to 0.68, P for linearity <0.0001). Also, after adjustment for high-density lipoprotein particle number and size, apoA-II was still associated with the risk of future CAD (odds ratio 0.62, 95% confidence interval 0.43 to 0.90, P for linearity 0.02). ApoA-II is associated with a decreased risk of future CAD in apparently healthy people. These findings imply that apoA-II itself exerts effects on specific antiatherogenic pathways. On the basis of these findings, discussion of the potential proatherogenic effects of apoA-II can cease.

Serum Myeloperoxidase Levels Are Associated With the Future Risk of Coronary Artery Disease in Apparently Healthy Individuals: The EPIC-Norfolk Prospective Population Study

We evaluated whether serum myeloperoxidase (MPO) levels are associated with the risk of future development of coronary artery disease (CAD) in apparently healthy individuals. An enzyme of the innate immune system, MPO exhibits a wide array of proatherogenic effects. These include induction of oxidative damage to low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and promotion of plaque vulnerability. Recent studies revealed that MPO independently predicts adverse outcomes in patients with chest pain or suspected acute coronary syndrome. Myeloperoxidase was measured in baseline samples of a case-control study nested in the prospective EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk population study. Case subjects (n = 1,138) were apparently healthy men and women who developed CAD during 8-year follow-up. Control subjects (n = 2,237), matched for age, gender, and enrollment time, remained free of CAD. The MPO levels were significantly higher in case subjects than in control subjects and correlated with C-reactive protein (CRP) (rho = 0.25; p < 0.001) and white blood cell count (rho = 0.33; p < 0.001). Risk of future CAD increased in consecutive quartiles of MPO concentration, with an odds ratio (OR) of 1.49 in the top versus bottom quartile (95% confidence interval [CI] 1.20 to 1.84; p < 0.001). After adjustment for traditional risk factors, the OR in the top quartile remained significant at 1.36 (95% CI 1.07 to 1.73). Elevated MPO levels (>728 pmol/l) similarly predicted increased risk of future CAD among participants with either LDL-cholesterol <130 mg/dl, HDL-cholesterol >50 mg/dl, or CRP <2.0 mg/l (OR 1.52 [95% CI 1.21 to 1.91], 1.59 [95% CI 1.24 to 2.05], and 1.42 [95% CI 1.14 to 1.77)], respectively). Elevated MPO levels predict future risk of CAD in apparently healthy individuals. This study suggests that inflammatory activation precedes the onset of overt CAD by many years.

Abstract 4204: Osteoprotegerin Levels and Risk of Future Cardiovascular Events in Apparently Healthy Men and Women: the Prospective EPIC-Norfolk Population Study 1993–2003

Introduction: The identification of osteoprotegerin (OPG) as a novel cardiovascular risk marker suggests an association between mediators of bone homeostasis and cardiovascular disease. OPG is a member of the tumour necrosis factor (TNF) superfamily, and functions as a soluble decoy receptor for RANKL. There is no epidemiological evidence that OPG levels predict future coronary events in healthy individuals. It was therefore our objective to study the prospective relationship between plasma levels of OPG and the risk of future CAD in such a population. Methods and Results: A nested case-control study among participants of the European prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study, a prospective population study of 25 663 men and women between 45 and 79 years of which 988 apparently healthy individuals developed coronary artery disease (CAD) were matched by sex and age with 1812 healthy controls which did not develop CAD. Baseline OPG was higher in cases than in controls [6957 pg/ml (5778 – 8727) vs. 6602 pg/ml (5434–8242) (p&lt;0.005) median and interquartile range], and significantly higher in women than men in both cases and controls. Using OPG quartiles based on the distribution among controls, baseline OPG levels were independently correlated with fatal and non fatal coronary events and the risk increased continuously (p for linearity= 0.008 men, p=0.01 women), also when adjusted for age, smoking, diabetes, body mass index, LDL, HDL, systolic blood pressure, this strong relationship still existed. When adjusted for log (CRP) as well, the OR in the highest OPG quartile was 2.17(0.86–5.49)(95% CI)(p=0.04) for women and 2.78 (1.45–5.32)(p&lt;0.001) for men. Conclusion: Among apparently healthy men and women, an elevated level of OPG is associated with increased risk of future fatal and non fatal CAD.

Serum Levels of Mannose-Binding Lectin and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women

To determine the association between serum levels of mannose-binding lectin (MBL) and the risk of future coronary artery disease (CAD) in apparently healthy men and women. We performed a prospective case-control study among apparently healthy men and women nested in the EPIC-Norfolk cohort. Baseline concentrations of MBL were measured in serum samples of 946 patients who experienced a myocardial infarction or died of CAD during follow-up, and 1799 matched controls who remained free of CAD. Among men, median MBL levels were 1.63 ng/mL (interquartile range [IQR]: 0.59 to 3.80) in cases and 1.20 ng/mL (IQR: 0.48 to 3.37) in controls. Among women, median MBL levels were 1.02 ng/mL (IQR: 0.43 to 2.95) in cases and 1.01 ng/mL (IQR: 0.43 to 2.94) in controls. After adjustment, the odds ratio in men for future CAD was 1.59 (95% confidence interval [CI]: 1.09 to 2.32; P for linearity=0.01) for those in the highest quartile compared with those in the lowest quartile. In women no such relation was observed. Elevated levels of MBL are associated with an increased risk of future CAD in apparently healthy men but not in women. The sex difference merits further exploration.

Fibrinogen plasma levels modify the association between the factor XIII Val34Leu variant and risk of coronary artery disease: the EPIC-Norfolk prospective population study.

The factor (F) XIII Val34Leu variant has been implicated in coronary artery disease (CAD). In vitro evidence suggests an interaction between this variant and fibrinogen concentrations in determining thrombus structure. To test whether this interaction is relevant in influencing coronary risk in apparently healthy individuals. In an 8-year prospective population study of 25 663 men and women, we compared 898 apparently healthy men and women developing incident CAD with 1580 matched controls. Overall, the FXIII Val34Leu variant was not associated with the risk of future CAD. However, a significant interaction existed between the Val34Leu variant and fibrinogen levels for the risk of future CAD (P = 0.004). Among people in the lowest tertile of fibrinogen concentrations, LeuLeu carriers had an odds ratio (OR) of 2.88 (95% confidence interval; CI 1.24-6.74) compared to wild-type individuals (P for linearity = 0.003). By contrast, among those in the highest fibrinogen tertile, LeuLeu carriers were had a lower risk than wild-type individuals (OR 0.47, 95% CI 0.18-1.17, P for linearity = 0.1). Our results suggest that a significant gene-covariate interaction exists between the FXIII Val34Leu variant and fibrinogen levels. Relationships between genotype and disease risk may be altered by biological covariates. Simplistic paradigms of gene or biomarker associations are unlikely to fully characterize disease risk in populations.

Serum Lipoprotein Lipase Concentration and Risk for Future Coronary Artery Disease

Lipoprotein lipase (LPL) is associated with coronary artery disease (CAD) risk, but prospective population data are lacking. This is mainly because of the need for cumbersome heparin injections, which are necessary for LPL measurements. Recent retrospective studies, however, indicate that LPL concentration can be reliably measured in serum that enabled evaluation of the prospective association between LPL and future CAD. LPL concentration was determined in serum samples of men and women in the EPIC-Norfolk population cohort who developed fatal or nonfatal CAD during 7 years of follow-up. For each case (n=1006), 2 controls, matched for age, sex, and enrollment time, were identified. Serum LPL concentration was lower in cases compared with controls (median and interquartile range: 61 [43-85] versus 66 [46-92] ng/mL; P<0.0001). Those in the highest LPL concentration quartile had a 34% lower risk for future CAD compared with those in the lowest quartile (odds ratio [OR] 0.66; confidence interval [CI], 0.53 to 0.83; P<0.0001). This effect remained significant after adjustment for blood pressure, diabetes, smoking, body mass index, and low-density lipoprotein (LDL) cholesterol (OR, 0.77; CI, 0.60-0.99; P=0.02). As expected from LPL biology, additional adjustments for either high-density lipoprotein cholesterol (HDL-C) or triglyceride (TG) levels rendered loss of statistical significance. Of interest, serum LPL concentration was positively linear correlated with HDL and LDL size. Reduced levels of serum LPL are associated with an increased risk for future CAD. The data suggest that high LPL concentrations may be atheroprotective through decreasing TG levels and increasing HDL-C levels.

Serum Levels of Type II Secretory Phospholipase A2 and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women

To study the prospective relationship between serum levels of type II secretory phospholipase A2 (sPLA2) and the risk of future coronary artery disease (CAD) in apparently healthy men and women. We conducted a prospective nested case-control study among apparently healthy men and women aged 45 to 79 years. Cases (n=1105) were people in whom fatal or nonfatal CAD developed during follow-up. Controls (n=2209) were matched by age, sex, and enrollment time. sPLA2 levels were significantly higher in cases than controls (9.5 ng/mL; interquartile range [IQR], 6.4 to 14.8 versus 8.3 ng/mL; IQR, 5.8 to 12.6; P<0.0001). sPLA2 plasma levels significantly correlated with age, body mass index, systolic blood pressure, high-density lipoprotein (HDL) cholesterol levels, and C-reactive protein (CRP) levels. Taking into account matching for sex and age and adjusting for body mass index, smoking, diabetes, systolic blood pressure, low-density lipoprotein cholesterol, HDL cholesterol, and CRP levels, the risk of future CAD was 1.34 (1.02 to 1.71; P=0.02) for people in the highest sPLA2 quartile, compared with those in the lowest (P for linearity=0.03). Elevated levels of sPLA2 were associated with an increased risk of future CAD in apparently healthy individuals. The magnitude of the association was similar to that observed between CRP and CAD risk, and both associations were independent.