Future Myocardial Infarction Research Articles

Polymorphism in the CETP Gene Region, HDL Cholesterol, and Risk of Future Myocardial Infarction

Background— Recent trial data have challenged the hypothesis that cholesteryl ester transfer protein (CETP) and high-density lipoprotein cholesterol (HDL-C) have causal roles in atherothrombosis. One method to evaluate this issue is to examine whether polymorphisms in the CETP gene that impact on HDL-C levels also impact on the future development of myocardial infarction. Methods and Results— In a prospective cohort of 18 245 initially healthy American women, we examined over 350 000 singe-nucleotide polymorphisms (SNPs) first to identify loci associated with HDL-C and then to evaluate whether significant SNPs within these loci also impact on rates of incident myocardial infarction during an average 10-year follow-up period. Nine loci on 9 chromosomes had 1 or more SNPs associated with HDL-C at genome-wide statistical significance ( P <5�10 −8 ). However, only SNPs near or in the CETP gene at 16q13 were associated with both HDL-C and risk of incident myocardial infarction (198 events). For example, SNP rs708272 in the CETP gene was associated with a per-allele increase in HDL-C levels of 3.1 mg/dL and a concordant 24% lower risk of future myocardial infarction (age-adjusted hazard ratio, 0.76; 95% CI, 0.62 to 0.94), consistent with recent meta-analysis. Independent and again concordant effects on HDL-C and incident myocardial infarction were also observed at the CETP locus for rs4329913 and rs7202364. Adjustment for HDL-C attenuated but did not eliminate these effects. Conclusion— In this prospective cohort of initially healthy women, SNPs at the CETP locus impact on future risk of myocardial infarction, supporting a causal role for CETP in atherothrombosis, possibly through an HDL-C mediated pathway.

Smoking cessation is associated with increased plasma adiponectin levels in men

Low levels of adiponectin, an adipocytokine with anti-diabetic and anti-atherogenic properties, are associated with increased risk of future myocardial infarction in men. Previous studies have demonstrated that cigarette smoking is involved in the development of insulin resistance, and current smokers have been shown to have reduced plasma adiponectin levels. However, the influence of smoking cessation on adiponectin levels remains unknown. We sought to assess whether smoking cessation is associated with increased plasma adiponectin levels in men. The study includes 72 men (47 non-smokers and 25 current smokers at baseline) with stable angina pectoris who underwent percutaneous coronary intervention and follow-up coronary angiography 6 months later. During the 6-month follow-up period, all 47 non-smokers remained non-smokers, while 15 men of the 25 baseline current smokers successfully quit smoking. We evaluated plasma adiponectin levels at coronary intervention and 6 months later. Plasma adiponectin levels at coronary intervention were comparable to those after 6 months in non-smokers (4.22 [3.15-6.43] vs. 4.58 [3.03-6.26] microg/mL, P=0.124) and in persistent smokers (4.77 [4.25-10.53] vs. 5.16 [4.11-8.10] microg/mL, P=0.721). Meanwhile, an increase in adiponectin level was observed in patients who quit smoking for 6 months (4.24 [3.30-5.70] vs. 5.50 [4.03-8.00] microg/mL, P=0.002). Univariate analysis revealed that the percent increase in adiponectin levels correlated positively with smoking cessation (P=0.003) and negatively with additional use of beta-blockers (P=0.049). In addition, increases in adiponectin levels were closely associated with increase in high-density lipoprotein cholesterol (P=0.148), decrease in triglycerides (P=0.140), and additional use of renin-angiotensin system inhibitors (P=0.069). Multivariate analysis demonstrated that smoking cessation was an independent determinant of the increase in adiponectin (P=0.036). Smoking cessation is associated with increased plasma adiponectin levels in men with stable angina, suggesting that the significance of smoking cessation may be partly explained by the increase in adiponectin level.

The metabolic syndrome and risk of myocardial infarction in familial hypertension (Hypertension Heredity in Malmö Evaluation study)

The aim of this study was to examine whether three main definitions of the metabolic syndrome (MetS)--WHO, National Cholesterol Education Program--Adult Treatment Panel III and International Diabetes Federation--identify the same individuals and are able to predict incident myocardial infarction (MI) in families with essential hypertension. The tested definitions were prospectively related to data on MI in a cohort of approximately 1700 individuals with overt essential hypertension and their normotensive first-degree relatives. At baseline, 616 participants had MetS, yet only 209 of them (33.9%) were identified by all definitions, and compatibility rate for each pair of definitions was approximately 50%. During follow-up (Tmean approximately 6.6 years) 53 participants developed MI and they were generally older and more dysmetabolic than the rest of the cohort. There were also more men, smokers and diabetic individuals in this group. After adjustment for all conventional cardiovascular risk factors, including hypertension and diabetes, only the National Cholesterol Education Program definition could predict the increased risk of MI [odds ratio (OR) = 2.2, confidence interval (CI) = 1.2-4.0, P = 0.01]. Among individual MetS components, incident MI was independently associated with three of them: low high-density lipoprotein-cholesterol (OR = 2.03, CI = 1.09-3.78, P = 0.025) insulin resistance (OR = 2.02, CI = 1.08-3.78, P = 0.028) and increased albumin excretion rate (OR = 1.24, CI = 0.99-1.55, P = 0.060). The presence of MetS in hypertensive and genetically hypertension prone individuals may signal the increased risk of future MI. However, only the National Cholesterol Education Program criteria appear to have a sufficient predictive accuracy.

Inflammatory markers for ischaemic stroke

Thromb Haemost 2009; 101: 800–801 Experimental and clinical evidence accumulated since 1990 have established inflammatory processes as important contributors to atherogenesis (1). Based upon this evidence, protein markers of inflammation have been studied as non-invasive indicators of underlying atherosclerosis in apparently healthy individuals and of the risk of cardiovascular events in patients with established atherosclerotic diseases. The most extensively studied biomarker of inflammation in cardiovascular diseases is C-reactive protein (CRP), an acute phase protein that is produced predominantly by hepatocytes under the influence of cytokines such as interleukin (IL)-6 and tumour necrosis factor (TNF)-α (2). Data from more than 30 epidemiologic studies have shown a significant association between elevated serum or plasma concentrations of CRP and the prevalence of underlying atherosclerosis, the risk of recurrent cardiovascular events among patients with established disease, and the incidence of first cardiovascular events among individuals at risk for atherosclerosis (3). Although it is plausible that CRP serum levels are increased as part of the acute phase response to inflammation, experimental evidence has also raised the possibility that CRP is a direct participant in the progression of atherosclerosis and its clinical consequences (4). Indeed, CRP infusion is associated with marked elevations in markers of both inflammation, such as IL-6, IL-8, and serum amyloid A, and coagulation, such as von Willebrand factor (vWF) antigen, prothrombin F1+2, D-dimer, and plasminogen activator inhibitor type 1 (PAI-1) (5). Regarding cerebrovascular diseases, the data in the literature indicate that CRP is an independent marker for the development and progression of early carotid atherosclerotic disease (6), the risk of ischaemic stroke (7), and the prognosis after stroke (8–10). In addition to CRP, other markers of inflammation are predictors of cardiovascular disease in healthy men and women. In men, plasma IL-6 concentrations have been shown to be predictive of a future myocardial infarction (11). Among patients with unstable or stable angina or even mild angiographic coronary disease, increased serum levels of IL-18 may be an independent predictor of cardiovascular mortality (12). One analysis found that circulating serum concentrations of soluble receptors for TNF-α are correlated with coronary risk among women (13). Other studies have found an association between the serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and P-selectin and the future development or exacerbation of cardiovascular diseases (14). Elevated serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin also may have predictive value (14). In a study published in the current issue of Thrombosis and Haemostasis, Licata and his collaborators add to our knowledge on immuno-inflammatory markers and ischaemic stroke (15). By studying individuals with different subtypes of ischaemic stroke, classified according to the TOAST scheme, they demonstrate that plasma levels of important inflammatory molecules, such as IL-6, TNF-α, and IL-1β, are significantly higher in subjects with stroke of cardio-embolic origin than in subjects with other subtypes of stroke. In addition, they show that, in subjects with stroke, neurological deficit at admission, as measured by the Scandinavian Stroke Scale (SSS), is significantly and independently correlated to IL-6 and TNF-α plasma levels. Licata’s findings are important for several reasons. First of all, they demonstrate that different subtypes of ischaemic stroke are associated with different levels of activation of inflammatory markers. Second, the demonstration that increased plasma levels of inflammatory cytokines are particularly evident in cardio-embolic strokes provides support to the hypothesis that inflammation may be associated with atrial fibrillation and contributes to the pathogenesis of arrhythmic disorders (16). Finally, the fact that IL-6 and TNF-α plasma levels correlate with stroke subtype and SSS score suggests that the evaluation of these inflammatory markers might be useful for a better characterisation of subjects suffering from acute ischaemic cerebrovascular diseases. These findings might have important implications for the clinical management of subjects affected by ischaemic cardiovascular diseases. © 2009 Schattauer GmbH, Stuttgart

Plasma Fetuin-A Levels and the Risk of Myocardial Infarction and Ischemic Stroke

Fetuin-A, a protein almost exclusively secreted by the liver, induces insulin resistance and subclinical inflammation in rodents. Circulating fetuin-A levels are elevated in humans with metabolic syndrome and insulin resistance, conditions that are associated with increased risk of cardiovascular disease. We investigated the association between fetuin-A levels and the risk of future myocardial infarction (MI) and ischemic stroke (IS) in a case-cohort study based on the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study comprising 27 548 middle-aged subjects of the general population. Fetuin-A levels were measured in plasma of 227 individuals who developed MI, in 168 who developed IS, and in 2198 individuals who remained free of cardiovascular events during a mean follow-up of 8.2+/-2.2 years. Individuals in the highest compared with the lowest quintile of plasma fetuin-A had significantly increased risks of MI (relative risk, 3.80; 95% confidence interval, 2.37 to 6.10; P for trend <0.0001) and IS (relative risk, 3.93; 95% confidence interval, 2.17 to 7.12; P for trend <0.0001) after adjustment for sex and age. Additional adjustment for smoking status, body mass index, waist circumference, alcohol consumption, educational attainment, physical activity, hypertension, diabetes mellitus, total and high-density lipoprotein cholesterol, and C-reactive protein only moderately attenuated these risks (MI: relative risk, 3.25; 95% confidence interval, 2.01 to 5.28; P for trend <0.0001; IS: relative risk, 3.78; 95% confidence interval, 2.06 to 6.94; P for trend <0.0001). Our data provide evidence for a link between high plasma fetuin-A levels and an increased risk of MI and IS. Therefore, more research is warranted to determine the role of fetuin-A in the pathophysiology of cardiovascular disease.

Predictive value of coronary calcifications for future cardiac events in asymptomatic patients with diabetes mellitus: A prospective study in 716 patients over 8 years

BackgroundTo establish an efficient prophylaxis of coronary artery disease reliable risk stratification is crucial, especially in the high risk population of patients suffering from diabetes mellitus. This prospective study determined the predictive value of coronary calcifications for future cardiovascular events in asymptomatic patients with diabetes mellitus.MethodsWe included 716 patients suffering from diabetes mellitus (430 men, 286 women, age 55.2 ± 15.2 years) in this study. On study entry all patients were asymptomatic and had no history of coronary artery disease. In addition, all patients showed no signs of coronary artery disease in ECG, stress ECG or echocardiography. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomograph. For quantification of coronary calcifications we calculated the Agatston score. After a mean observation period of 8.1 ± 1.1 years patients were contacted and the event rate of cardiac death (CD) and myocardial infarction (MI) was determined.ResultsDuring the observation period 40 patients suffered from MI, 36 patients died from acute CD. The initial Agatston score in patients that suffered from MI or died from CD (475 ± 208) was significantly higher compared to those without cardiac events (236 ± 199, p < 0.01). An Agatston score above 400 was associated with a significantly higher annualised event rate for cardiovascular events (5.6% versus 0.7%, p < 0.01). No cardiac events were observed in patients with exclusion of coronary calcifications. Compared to the Framingham risk score and the UKPDS score the Agatston score showed a significantly higher diagnostic accuracy in the prediction of MI with an area under the ROC curve of 0.77 versus 0.68, and 0.71, respectively, p < 0.01.ConclusionBy determination of coronary calcifications patients at risk for future MI and CD could be identified within an asymptomatic high risk group of patients suffering from diabetes mellitus. On the other hand future events could be excluded in patients without coronary calcifications.

The velocity of the arterial pulse wave: a viscous-fluid shock wave in an elastic tube

BackgroundThe arterial pulse is a viscous-fluid shock wave that is initiated by blood ejected from the heart. This wave travels away from the heart at a speed termed the pulse wave velocity (PWV). The PWV increases during the course of a number of diseases, and this increase is often attributed to arterial stiffness. As the pulse wave approaches a point in an artery, the pressure rises as does the pressure gradient. This pressure gradient increases the rate of blood flow ahead of the wave. The rate of blood flow ahead of the wave decreases with distance because the pressure gradient also decreases with distance ahead of the wave. Consequently, the amount of blood per unit length in a segment of an artery increases ahead of the wave, and this increase stretches the wall of the artery. As a result, the tension in the wall increases, and this results in an increase in the pressure of blood in the artery.MethodsAn expression for the PWV is derived from an equation describing the flow-pressure coupling (FPC) for a pulse wave in an incompressible, viscous fluid in an elastic tube. The initial increase in force of the fluid in the tube is described by an increasing exponential function of time. The relationship between force gradient and fluid flow is approximated by an expression known to hold for a rigid tube.ResultsFor large arteries, the PWV derived by this method agrees with the Korteweg-Moens equation for the PWV in a non-viscous fluid. For small arteries, the PWV is approximately proportional to the Korteweg-Moens velocity divided by the radius of the artery. The PWV in small arteries is also predicted to increase when the specific rate of increase in pressure as a function of time decreases. This rate decreases with increasing myocardial ischemia, suggesting an explanation for the observation that an increase in the PWV is a predictor of future myocardial infarction. The derivation of the equation for the PWV that has been used for more than fifty years is analyzed and shown to yield predictions that do not appear to be correct.ConclusionContrary to the theory used for more than fifty years to predict the PWV, it speeds up as arteries become smaller and smaller. Furthermore, an increase in the PWV in some cases may be due to decreasing force of myocardial contraction rather than arterial stiffness.

Family history of myocardial infarction is an independent risk factor for venous thromboembolism: the Tromsø study.

Recent studies indicate that arterial cardiovascular diseases and venous thromboembolism (VTE) share common risk factors. A family history of myocardial infarction (MI) is a strong and independent risk factor for future MI. The purpose of the present study was to determine the impact of cardiovascular risk factors, including family history of MI, on the incidence of VTE in a prospective, population-based study. Traditional cardiovascular risk factors and family history of MI were registered in 21,330 subjects, aged 25-96 years, enrolled in the Tromsø study in 1994-95. First-lifetime VTE events during follow-up were registered up to 1 September 2007. There were 327 VTE events (1.40 per 1000 person-years), 138 (42%) unprovoked, during a mean of 10.9 years of follow-up. In age- and gender-adjusted analysis, age [hazard ratio (HR) per decade, 1.97; 95% confidence interval (CI), 1.82-2.12], gender (men vs. women; HR, 1.25; 95% CI, 1.01-1.55), body mass index (BMI; HR per 3 kg m(-2), 1.21; 95% CI, 1.13-1.31), and family history of MI (HR, 1.31; 95% CI, 1.04-1.65) were significantly associated with VTE. Family history of MI remained a significant risk factor for total VTE (HR, 1.27; 95% CI, 1.01-1.60) and unprovoked VTE (HR, 1.46; 95% CI, 1.03-2.07) in multivariable analysis. Blood pressure, total cholesterol, HDL-cholesterol, triglycerides, and smoking were not independently associated with total VTE. Family history of MI is a risk factor for both MI and VTE, and provides further evidence of a link between venous and arterial thrombosis.

Acute Coronary Syndrome

The effectiveness of therapy for an acute coronary syndrome (ACS) is dependent on patients' quick decision to seek treatment. We surveyed patients' level of knowledge about heart disease and self-perceived risk for a future acute myocardial infarction (AMI) in patients with documented ischemic heart disease. Patients (N = 3522) had a mean age of 67 years, 68% were male, and all had a history of AMI or invasive cardiac procedure for ischemic heart disease. Data were gathered using a 26-item instrument focusing on ACS symptoms and appropriate steps to seeking treatment. Patients were asked to identify their level of perceived risk for a future AMI. Forty-six percent of patients had low knowledge levels (ie, <70% of answers were correct). The mean score was 71%. Higher knowledge scores were significantly related to female sex (P = .001), younger age (P = .001), higher education (P = .001), participation in cardiac rehabilitation (P = .001), and receiving care by a cardiologist rather than an internist or general practitioner (P = .005). Clinical history (eg, AMI [P = .24] and cardiac surgery [P = .38]) were not significant predictors of knowledge. Most (57%) identified themselves as being at higher risk for a future AMI compared with an age-matched individual without heart disease with 1 exception. Namely, patients who had undergone coronary artery bypass surgery felt significantly less vulnerable for a future AMI than other individuals of the same age. Even following diagnosis of ACS and numerous interactions with physicians and other health care professionals, knowledge about ACS symptoms and treatment on the part of patients with cardiac disease remains poor. Patients require continued reinforcement about the nature of cardiac symptoms, the benefits of early treatment, and their risk status.

Plasma Resistin Levels and Risk of Myocardial Infarction and Ischemic Stroke

Resistin is a hormone that has been linked to insulin resistance, inflammatory processes, and coronary heart disease in case-control studies; however, prospective data on the association between plasma resistin levels and future risk of cardiovascular disease are lacking. The objective of the study was to investigate the association between plasma resistin levels and risk of future myocardial infarction (MI) and ischemic stroke (IS) in a large prospective cohort. We investigated the association between plasma resistin levels and risk of MI and IS in a case-cohort design among 26,490 middle-aged subjects from the European Investigation into Cancer and Nutrition-Potsdam Study without history of MI or stroke at time of blood draw. Plasma resistin levels were measured in baseline blood samples of 139 individuals who developed MI, 97 who developed IS, and 817 individuals who remained free of cardiovascular events during a mean follow-up of 6 yr. After multivariable adjustment for established cardiovascular risk factors including C-reactive protein, individuals in the highest compared with the lowest quartile of plasma resistin levels had a significantly increased risk of MI (relative risk 2.09; 95% confidence interval 1.01-4.31; P for trend = 0.01). In contrast, plasma resistin levels were not significantly associated with risk of IS (relative risk 0.94; 95% confidence interval 0.51-1.73; P for trend = 0.88). Our data suggest that high plasma resistin levels are associated with an increased risk of MI but not with risk of IS. Further studies are needed to evaluate the predictive value of plasma resistin levels for cardiovascular disease.

The metabolic syndrome and cardiovascular risk: implications for clinical practice

The clinical importance of the metabolic syndrome (MeS) is confused by the existence of at least three different definitions proposed by prominent organizations, and by a lack of information about the prognostic value of diagnosing a person as having the syndrome by any of the definitions. We used the US National Health and Nutrition Evaluation Survey (NHANES) to determine the prevalence in the United States of the variables used to define the MeS and cardiovascular disease (CVD), and to create a simulated population that matched the US population with respect to all the important characteristics, risk factors and treatments for CVD. We then used the Archimedes model to calculate the long-term CVD outcomes for each person in the simulated population. The definitions implied an increased risk of CVD of 1.5-1.6. The definitions varied considerably in their ability to identify people at risk of myocardial infarctions (MIs); the proportion of people destined to have a future MI captured by the different definitions varied from 57 to 77%. The definitions also varied widely in how well they ruled out future MIs; failure to have MeS by a definition still left a chance of a future MI ranging from 23 to 42%. The definitions differed importantly in which people they identified as having MeS; 34% of those who met the ATP definition did not meet the WHO definition, 30% of those who met the WHO definition did not meet the ATP definition and 28% of those who met the IDF definition did not meet the ATP definition. Of the components of the definitions, the most important single factor for identifying a person at risk of future CVD was high glucose, with hypertension, obesity, high triglycerides and low HDL following in that order. High glucose, by itself, was as good as any definition of the MeS in predicting risk of future MI. Whichever definition was used, individuals who met the definition varied widely in their risk of CVD. For assessing a particular person's risk of future CVD and for making treatment decisions a diagnosis of MeS by any of the definitions added little if anything to assessing each person's risk factors.

Management of Chronic Coronary Disease: Is the Pendulum Returning to Equipoise?

Over the last 3 decades, our ability to mechanically dilate obstructive coronary arterial stenoses has fundamentally altered our approach to managing patients with coronary artery disease (CAD). The result has been a swing from an initial pharmacologic approach to anatomically driven revascularization. An accumulation of clinical evidence provides strong support for such intervention in acute coronary syndromes (ACS). In stable CAD, dilative therapy was believed to be superior based on the assumption that high-risk coronary anatomy or myocardial ischemia increases the risk of future death and myocardial infarction. However, there have been major advances in our understanding of the pathophysiology of ACS and the recognition of the significance of predisposing non-flow-limiting coronary stenoses prone to rupture, as well as increasing insight into plaque and patient vulnerability. This improved understanding of the disease has led to the more aggressive use of appropriately targeted pharmacologic agents and an evolution in what constitutes optimal medical therapy (OMT). Data from recent studies, such as the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, support the concept that in patients with stable CAD, OMT alone in this day and age compares favorably with a therapeutic strategy combining OMT with mechanical intervention. Thus, the treatment pendulum may be swinging back to the understanding that "best practice" today requires the judicious use of interventional and medical therapies in the appropriate patient population.

Stress Testing Prior to Percutaneous Coronary Intervention

Most patients who receive percutaneous coronary intervention (PCI) have stable coronary artery disease. Because PCI in these patients is not superior to optimal medical therapy in lowering excess risk for cardiovascular death or future myocardial infarction, clinical practice guidelines strongly recommend the documentation of moderate-to-severe ischemia through stress …

Predictive value of coronary calcifications for future cardiac events in asymptomatic individuals

Reliable risk stratification is crucial for efficient prevention of coronary artery disease. The following prospective study determined the predictive value of coronary calcifications for future cardiovascular events. We included 1726 asymptomatic individuals (1018 men, 708 women, age 57.7 +/- 13.3 years) referred for a cardiological examination. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomography scanner. For quantification of coronary calcifications, we calculated the Agatston score. Over a mean observation period of 40.3 +/- 7.3 months we registered the event rate for cardiac death (CD) and myocardial infarction (MI). The Agatston score in patients who died of CD (n = 65) or had an MI (n = 114) was significantly higher compared with those without cardiac events (458 +/- 228 vs 206 +/- 201, P < .01). An Agatston score above the 75th percentile was associated with a significantly higher annualized event rate for MI (3.6% vs 1.6%, P < .05) and for CD (2.2% vs 0.9%) compared with patients with scores below the 75th percentile. No cardiac events were observed in patients where coronary calcifications could be excluded. By determination of coronary calcifications, patients at risk for future MI and CD could be identified within an asymptomatic population independent of concomitant risk factors. At the same time, future cardiovascular events could be excluded in patients without coronary calcifications.

Protein carbamylation links inflammation, smoking, uremia and atherogenesis

Post-translational modification and functional impairment of proteins through carbamylation is thought to promote vascular dysfunction during end-stage renal disease. Cyanate, a reactive species in equilibrium with urea, carbamylates protein lysine residues to form epsilon-carbamyllysine (homocitrulline), altering protein structure and function. We now report the discovery of an alternative and quantitatively dominant mechanism for cyanate formation and protein carbamylation at sites of inflammation and atherosclerotic plaque: myeloperoxidase-catalyzed oxidation of thiocyanate, an anion abundant in blood whose levels are elevated in smokers. We also show that myeloperoxidase-catalyzed lipoprotein carbamylation facilitates multiple pro-atherosclerotic activities, including conversion of low-density lipoprotein into a ligand for macrophage scavenger receptor A1 recognition, cholesterol accumulation and foam-cell formation. In two separate clinical studies (combined n = 1,000 subjects), plasma levels of protein-bound homocitrulline independently predicted increased risk of coronary artery disease, future myocardial infarction, stroke and death. We propose that protein carbamylation is a mechanism linking inflammation, smoking, uremia and coronary artery disease pathogenesis.

A prospective study of oral contraceptive use and risk of myocardial infarction among Swedish women

To determine the risk for incident myocardial infarction (MI) in women exposed to modern formulations of oral contraceptives (OCs). Population-based, prospective cohort study begun in 1991 with follow-up through 2002 for an average of 11 years. A total of 48,321 Swedish women aged 30-49 randomly selected from the population residing in the Uppsala Health Care Region of Sweden in 1990-91. Fatal and nonfatal MI ascertained through linkages with nationwide health registries for death, hospitalization, and emigration. There were 214 incident cases of MI. Compared with never users, neither former (relative risk, 1.0; 95% confidence interval, 0.7-1.4) nor current (relative risk, 0.7; 95% confidence interval, 0.4-1.4) OC users at study enrollment had an elevated risk of future MI in models adjusted for coronary heart disease risk factors. Risk of MI was not elevated by prolonged use or in subgroups defined by characteristics of the women or types of OC. Use of OC was not associated with an increased risk of MI in this prospective study, in which most current users of OC were taking low-dose estrogen and second- or third-generation progestins.

Increased carotid intima media thickness and cardiac biomarkers in HIV infected children

To assess carotid intima media thickness (IMT) and cardiac biomarkers in HIV infected children on antiretroviral therapy (ART). This was a single site, cross sectional, controlled observational study. We assessed carotid IMT, homocysteine, high-sensitivity C-reactive protein and myeloperoxidase levels in HIV infected children on stable ART for >or= 6 months. Carotid IMT was reported as internal carotid artery (ICA) and common carotid artery (CCA) thickness; left and right sides were measured separately. Groups were compared using appropriate two-sample tests. Of the 62 subjects enrolled, 31 were HIV positive (50%), 66% were female, and 69% were African-American. Median CD4% was 32% and 26 patients (84%) had HIV-1 RNA< 400 copies/ml. Sixteen patients had been taking protease inhibitors for a median duration of 27 months. None had hypertension or smoked. HIV infected children had higher HOMA-IR, waist-to-hip ratio, cholesterol, triglycerides, myeloperoxidase and lower homocysteine levels. Left and right CCA IMT, and left and right ICA IMT were significantly higher in the HIV infected group. Significant predictors of carotid IMT measurements in uninfected controls were body mass index and homocysteine, but only the duration of ARV therapy was predictive of IMT in the HIV infected group. Higher levels of carotid IMT and some cardiac markers were found in ART treated HIV infected children when compared to matched uninfected controls. These results suggest that HIV infected children receiving ART may be at increased risk of cardiovascular disease.

Comparison of Characteristics of Future Myocardial Infarctions in Women With Baseline High Versus Baseline Low Levels of High-Sensitivity C-Reactive Protein

High-sensitivity C-reactive protein (hs-CRP) has previously been shown to be an independent predictor for the development of cardiovascular disease. However, little is known about the association between hs-CRP and the severity of cardiovascular events that occur. This study compared characteristics of incident myocardial infarctions (MIs) in 40 initially healthy women with very high baseline hs-CRP levels (>7.5 mg/L) with infarctions in 40 women with very low hs-CRP levels (< or =1 mg/L). At baseline, very high hs-CRP was associated with a clinical diagnosis of hypertension, higher body mass index, lower high-density lipoprotein, and higher triglycerides. Our analysis found that the 2 study groups had similar proportions of ST-segment elevations on electrocardiograms, peak cardiac enzyme levels, postinfarct left ventricular function, and burden of coronary atherosclerosis seen on angiography. However, subjects with very high hs-CRP levels developed infarctions significantly sooner than those with very low hs-CRP levels (median time to event 4.45 vs 6.64 years, respectively, p <0.0001). In addition, higher baseline levels of hs-CRP were associated with significantly more fatal MIs (0% vs 4.6% vs 9.6% in subjects with hs-CRP levels <1, 1 to <3, and > or =3 mg/L, respectively, p for trend = 0.02). In conclusion, this study demonstrates that in initially healthy women high levels of hs-CRP predict earlier occurrence of MIs and a greater likelihood that infarctions will be fatal.

Acute Myocardial Infarction in Patients With Versus Without Aortic Valve Sclerosis and Effect of Statin Therapy (from the Heart and Soul Study)

Aortic sclerosis is associated with cardiovascular events in patients without coronary heart disease (CHD), but it is unclear whether this association exists in patients with established CHD or is independent of baseline cardiac disease severity. It is also unclear whether statins modify this association. In a prospective cohort study of 814 outpatients with established CHD and no evidence of aortic stenosis, the association of aortic sclerosis with subsequent cardiovascular events was examined using a multivariable Cox proportional hazards model. Of 814 participants, 324 (40%) had aortic sclerosis. During 4 years of follow-up, 10% with aortic sclerosis experienced a myocardial infarction (MI) compared with 5% of those without aortic sclerosis (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.1 to 3.1, p = 0.02). This association was unchanged after adjustment for potential confounders and mediators (HR 2.4, 95% CI 1.3 to 4.8, p = 0.009). However, the association between aortic sclerosis and MI appeared to differ by statin use (p = 0.15 for interaction). Aortic sclerosis predicted subsequent MI in subjects not administered statins (adjusted HR 4.1, 95% CI 1.1 to 15.7, p = 0.04), but not in those administered statins (adjusted HR 1.7, 95% CI 0.8 to 3.9, p = 0.18). In conclusion, aortic sclerosis was present in 40% of patients with CHD and is independently associated with a 2.4-fold increased rate of subsequent MI. Statins may attenuate the increased risk of future MI in patients with aortic sclerosis.

Early invasive treatment benefits patients with renal dysfunction in unstable coronary artery disease

Few studies have investigated the effects of an early revascularization in relation to renal function in patients with unstable coronary artery disease (CAD). Patients (n = 2457) with unstable CAD randomized to a noninvasive or invasive treatment strategy in the Fast Revascularisation during InStability in Coronary artery disease (FRISC-II) trial were stratified according to tertiles of creatinine clearance (CrCl < 69 mL/min, CrCl 69-90 mL/min, CrCl > 90 mL/min) and followed for 2 years regarding death and/or myocardial infarction (MI). In the noninvasive cohort, the rate of death or MI at 2 years was 22.4% at CrCl < 69 mL/min, 14.6% at CrCl 60-90 mL/min, and 11.6% at CrCl > 90 mL/min. In the invasive cohort, the rate of death or MI was reduced to 14.6% (P = .003) at CrCl < 69 mL/min and to 9.9% (P = .048) at CrCl 69 to 90 mL/min, but no significant reduction (11.2%) at CrCl > 90 mL/min. In a logistic regression analysis adjusting for other important covariables, CrCl < 69 mL/min remained independently associated with the risk of the combined end point in the noninvasively treated group (odds ratio, 1.96; 95% confidence interval, 1.12-3.42) but not in the invasively treated group (odds ratio, 1.09; 95% confidence interval, 0.56-2.14). When the interaction term for treatment strategy and CrCl group was included in the analysis, the interaction between treatment strategy and CrCl <90 mL/min was independently associated with the risk of future MI (P = .006). In unstable CAD, an early invasive treatment strategy reduces the long-term risk of future death and MI in patients with mildly to moderately reduced CrCl.