Progressing From Risk Factors to Omics

At least 25% of coronary patients have sudden death or nonfatal myocardial infarction without prior symptoms.1 Therefore, the search for coronary patients with subclinical disease who could potentially benefit from intensive primary prevention efforts is critically important. The American Heart Association’s (AHA) Prevention V Conference, “Beyond Secondary Prevention: Identifying the High Risk Patient for Primary Prevention,” addressed ways to identify more patients who are asymptomatic and clinically free of coronary heart disease (CHD) but at sufficiently high risk for a future coronary event to justify more intensive risk reduction efforts.2 In this report, we amplify on key findings and recommendations of the AHA Prevention V conference, highlight new research since the conference, and propose an approach to the use of office-based testing and additional noninvasive procedures in selected patients to better define their coronary event risk. The recommendations are concordant with the recently released approach to risk assessment and management from the third report of the Adult Treatment Panel of the National Cholesterol Education Program (ATP-III).3 Enthusiasm for primary prevention and risk assessment in asymptomatic people has been spurred by recent advances in prevention research. Lipid-lowering trials demonstrated that primary prevention of coronary events is feasible, evidenced by the West of Scotland Coronary Primary Prevention Study (WOSCOPS) trial4 of hypercholesterolemic men and by the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) trial5 in average or typical risk men and women with only moderate lipid abnormalities. Aspirin6 or ACE inhibitors7 can also reduce risk in selected asymptomatic, high-risk people. Emerging coronary risk factors have been described including inflammatory, infectious, and thrombotic markers,8 and there has been a steady flow of reports that focus attention on potential new ways of predicting coronary risk.9 In addition, noninvasive tests for subclinical atherosclerotic disease are available …

<i>Circulation</i> Editors’ Picks

Atherosclerosis and Vascular Biology

CRP-Marker or Maker of Cardiovascular Disease?Jan Nilsson C -reactive protein (CRP) has emerged as an interesting novel and potentially clinically useful marker for increased cardiovascular risk. 1,2This is an attractive concept because atherosclerosis is a disease characterized by chronic arterial inflammation 3,4 and suggests the possibility that subclinical states of atherosclerosis can be identified by an increase in circulating markers of inflammation before acute events occur.Based on data obtained primarily from in vitro studies it has also been proposed that CRP in itself is actively contributing to disease progression and that it should be considered as true risk factor and consequently as a target for intervention.However, in the present issue of Arteriosclerosis, Thrombosis, and Vascular Biology, two independent reports demonstrate that transgenic overexpression of CRP does not affect the development of atherosclerosis in mice, suggesting that this is not the case.

Diabetes has been shown to increase the risk of coronary heart disease in all populations studied. However, there is a lack of information on the relative importance of diabetes-associated risk factors for cardiovascular disease (CVD), especially the role of lipid levels, because low density lipoprotein (LDL) cholesterol often is not elevated in diabetic individuals. The objective of this analysis was to evaluate CVD risk factors in a large cohort of diabetic individuals and to compare the importance of dyslipidemia (ie, elevated triglycerides and low levels of high density lipoprotein [HDL] cholesterol) and LDL cholesterol in determining CVD risk in diabetic individuals. The Strong Heart Study assesses coronary heart disease and its risk factors in American Indians in Arizona, Oklahoma, and South/North Dakota. The baseline clinical examinations (July 1989 to January 1992) consisted of a personal interview, physical examination, and drawing of blood samples for 4549 study participants (2034 with diabetes), 45 to 74 years of age. Follow-up averaged 4.8 years. Fatal and nonfatal CVD events were confirmed by standardized record review. Participants with diabetes, compared with those with normal glucose tolerance, had lower LDL cholesterol levels but significantly elevated triglyceride levels, lower HDL cholesterol levels, and smaller LDL particle size. Significant independent predictors of CVD in those with diabetes included age, albuminuria, LDL cholesterol, HDL cholesterol (inverse), fibrinogen, and percent body fat (inverse). A 10-mg/dL increase in LDL cholesterol was associated with a 12% increase in CVD risk. Thus, even at concentrations well below the National Cholesterol Education Program target of 130 mg/dL, LDL cholesterol is a strong independent predictor of coronary heart disease in individuals with diabetes, even when components of diabetic dyslipidemia are present. These results support recent recommendations for aggressive control of LDL cholesterol in diabetic individuals, with a target level of <100 mg/dL.

Recognizing Pregnancy-Associated Cardiovascular Risk Factors

This study aimed to evaluate the relationship between low-density lipoprotein cholesterol (LDL-C) levels and cardiovascular disease (CVD) in high-risk patients with hypercholesterolemia without a history of CVD. Patients who were receiving or started treatment with pravastatin, were followed-up for 2 years. Patients were divided into quartiles according to on-treatment LDL-C. The maximum contrast method based on the Cox proportional hazards model was used to evaluate the relationship between achieved LDL-C and the incidence of CVD. Incidence of CVD was also compared according to whether a number of risk factor targets were achieved. A total 6,229 patients were enrolled, with 4,916 having reported LDL-C values. During the 2 years, 69 cases of CVD (6.7/1000 patient years), including 36 coronary artery disease (CAD) (3.5/1000 patient years) and 28 strokes (2.7/1000 patient years), occurred. The comparison of on-treatment LDL-C level quartiles suggested that the incidence of all CVD decreased linearly as the LDL-C levels decreased. Incidence of CAD showed a curvilinear relationship to LDL-C levels, suggesting some attenuation of risk below LDL-C of 119 mg/dL. The incidence of all CVD and CAD tended to be decreased as the number of achieved risk factor targets increased. In conclusion, through our observational study, it was shown that a linear relationship between the incidence of CVD and LDL-C was observed in high-risk hypercholesterolemic patients. The low incidence of CVD in the present study may be associated with multifactorial management of conventional risk factors including high LDL-C levels. However, prospective, randomized studies are needed to confirm these findings.

Heart Disease and Stroke Statistics—2009 Update

Should Lipoprotein(a) be Measured in Youth?

Cardiology Patient Page. C-reactive protein: a simple test to help predict risk of heart attack and stroke.

We evaluated data on blacks and whites with acute ST-segment-elevation myocardial infarction treated with either fibrinolysis or primary percutaneous coronary intervention from the National Registry of Myocardial Infarction (NRMI)-4 and -5 participating centers between July 2000 and December 2006 to determine race-related differences in bleeding and outcomes. We found that among patients with ST-segment-elevation myocardial infarction receiving fibrinolysis, the bleeding rates were higher for blacks (n2283) than whites (n42 243; 10.9% versus 10.3%; adjusted odds ratio, 1.21; 95% confidence interval, 1.02-1.43). Similarly, in patients receiving primary percutaneous coronary intervention, the bleeding rates were higher in blacks (n2826) than whites (n46 332; 10.3% versus 7.8%; adjusted odds ratio, 1.33; 95% confidence interval, 1.13-1.56). Bleeding was associated with a higher risk of death in both ethnic groups. However, there was no overall racial difference in in-hospital mortality among those with bleeding or without bleeding treated with either fibrinolysis or primary percutaneous coronary intervention. We concluded that race-related differences existed in bleeding risk among patients with ST-segmentelevation myocardial infarction receiving reperfusion therapy that portend poor prognosis. Thus, the efficacy and safety of many new drugs or treatment strategies for any disease observed in clinical trials that enroll predominantly white patients may not be similar in other ethnic groups that are underrepresented in these trials.

An Evidence-Based Review of Exercise and Metabolic Syndrome

Search for an Optimal Atherogenic Lipid Risk Profile: From the Framingham Study

Patients with inflammatory bowel disease have increased risks of cardiovascular diseases, but the role of traditional and non-traditional cardiovascular risk factors remains unclear. We investigated if the cardiovascular risk profile differs between patients with inflammatory bowel disease and individuals in the general population. We included a population of 108789 participants from the Copenhagen General Population Study of individuals of Danish descent aged 20-100 years. The population included 1203 individuals with prevalent inflammatory bowel disease [347 with Crohn's disease and 856 with ulcerative colitis]. The cardiovascular risk profile was assessed by traditional risk factors [plasma lipids and glucose, body composition measures, and blood pressure] and non-traditional risk factors [inflammatory markers and biomarkers of liver and pancreas function]. Even though patients with inflammatory bowel disease more frequently are diagnosed with cardiovascular diseases, traditional cardiovascular risk factors were not increased. Indeed, patients with inflammatory bowel disease had slightly lower plasma levels of total cholesterol and low-density lipoprotein cholesterol. Levels of inflammatory markers, particularly high-sensitivity C-reactive protein, were higher in individuals with versus without a diagnosis of inflammatory bowel disease, when assessed at a random point in time during the disease course. The increased risk of cardiovascular diseases in patients with inflammatory bowel disease may be linked to chronic systemic inflammation rather than to traditional cardiovascular risk factors. Further studies need to examine whether cardiovascular-preventive strategies should focus on optimising management of inflammation in patients with inflammatory bowel disease rather than focusing on traditional cardiovascular risk factors.

Received October 16, 2004; revision received June 4, 2005; accepted June 7, 2005. Atherosclerosis is a multifactorial process that commences in childhood but manifests clinically later in life. Atherosclerosis is increasingly considered an immune system–mediated process of the vascular system. The presence of macrophages and activated lymphocytes within atherosclerotic plaques supports the concept of atherosclerosis as an immune system–mediated inflammatory disorder.1,2 Inflammation can aggravate atherosclerosis via different mechanisms secondary to autoimmunity, infectious diseases, and other proatherogenic changes that occur during the inflammatory state. Autoimmune rheumatic diseases (AIRDs) are associated with higher rates of cardiovascular morbidity and mortality, primarily secondary to accelerated atherosclerosis. This phenomenon can be attributed to traditional risk factors for atherosclerosis and use of specific drugs, such as corticosteroids, but also might be the result of other autoimmune and inflammatory mechanisms that are aggravated in AIRDs. Several AIRDs exhibit increased overt cardiovascular disease (CVD) prevalence as well as findings of advanced subclinical atherosclerosis, which may precede the appearance of a clinical disease and thus be a target of early identification and preventive therapy. Cells of the immune system can be found within atherosclerotic plaques, which suggests that they have a role in the atherogenic process. Their migration and activation within the plaques can be secondary to various stimuli, including infectious agents.3 These cells probably aggravate atherosclerosis, because CD4+ and CD8+ T-cell depletion reduced fatty streak formation in C57BL/6 mice. In addition, after crossing of apolipoprotein E (ApoE)-knockout mice with immunodeficient scid/scid mice, the offspring had a 73% reduction in aortic fatty streak lesions compared with the immunocompetent apoE mice. Moreover, when CD4+ T cells were transferred from the immunocompetent to the immunodeficient mice, they increased lesion area in the latter by 164%.4 It is therefore not surprising that as in autoimmune diseases, the cellular components …