Coronary Risk Score Research Articles

Endothelial Progenitor Cells During Cerebrovascular Disease

Endothelial progenitor cells (EPCs) are associated with endothelial repair after ischemia in cardiac or peripheral circulation. There are no reports of EPCs with cerebrovascular disease. We present our experience with EPCs in patients with cerebrovascular disease. EPC counts differed significantly (P<0.001) between stroke patients (acute stroke: median 4.75 and range 0 to 33; stable stroke: median 7.25 and range 0 to 43) and control subjects (median 15.5 and range 4.3 to 50), independent of age. The level of EPCs was significantly correlated with the Framingham coronary risk score (FCRS) (rho=-0.349; P=0.002). Similar to cardiac experience, the low EPC levels may play a role in the pathophysiology of cerebrovascular disease.

The A1166C polymorphism of the angiotensin II type-1 receptor in acute myocardial infarction.

To assess the association of the A1166C polymorphism of the angiotensin II type-1 receptor (AT1R) gene with acute myocardial infarction and also with the severity of coronary artery disease. A prospective, cross-sectional study was carried out with 110 patients with acute myocardial infarction, who, on coronary angiography, had significant lesions (> 50%) assessed according to 3 criteria of severity: number of vessels affected, morphology of the atherosclerotic plaque, and coronary risk score. The control group comprised 104 individuals with no coronary lesions. The A1166C polymorphism of AT1R gene was determined by polymerase chain reaction in the DNA of leukocytes in peripheral blood. The classic coronary risk factors were analyzed in all individuals. When stratifying the genotypes in regard to risk factors, only smoking predominated in the AC heterozygous patients (P = 0.02). The genotypic frequency in the infarcted patients was as follows: AA = 54.5%; AC = 35.5%; and CC = 10%, which was similar and nonsignificant in regard to that in the control group (P = 0.83). No risk increase occurred for acute myocardial infarction when comparing the genotypes as follows: CC vs AA (OR = 1.35; 95% CI = 0.50 - 3.59); AC vs AA (OR = 1.03; 95% CI = 0.58 - 1.84); and AA+AC vs AA (OR = 1.33; 95% CI = 0.51 - 3.45). None of the severity criteria showed a significant correlation with the genotypes. According to our results, no correlation exists between the A1166C polymorphism of the angiotensin II type-1 receptor (AT1R) gene and acute myocardial infarction or the severity of coronary artery disease.

High-sensitivity C-reactive proteinClinical importance

High-sensitivity C-reactive protein (hsCRP) is a marker of inflammation that predicts incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death among healthy individuals with no history of cardiovascular disease, and recurrent events and death in patients with acute or stable coronary syndromes. hsCRP confers additional prognostic value at all levels of cholesterol, Framingham coronary risk score, severity of the metabolic syndrome, and blood pressure, and in those with and without subclinical atherosclerosis. hsCRP levels of less than 1, 1 to 3, and greater than 3 mg/L are associated with lower, moderate, and higher cardiovascular risks, respectively. This article summarizes epidemiologic data on the relation between CRP and atherothrombotic disease and provides clinical guidelines for hsCRP screening in cardiovascular risk assessment.

High-sensitivity C-reactive protein: Clinical importance

High-sensitivity C-reactive protein (hsCRP) is a marker of inflammation that predicts incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death among healthy individuals with no history of cardiovascular disease, and recurrent events and death in patients with acute or stable coronary syndromes. hsCRP confers additional prognostic value at all levels of cholesterol, Framingham coronary risk score, severity of the metabolic syndrome, and blood pressure, and in those with and without subclinical atherosclerosis. hsCRP levels of less than 1, 1 to 3, and greater than 3 mg/L are associated with lower, moderate, and higher cardiovascular risks, respectively. This article summarizes epidemiologic data on the relation between CRP and atherothrombotic disease and provides clinical guidelines for hsCRP screening in cardiovascular risk assessment.

Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk?

Of novel risk factors for cardiovascular disease currently under investigation, high-sensitivity C-reactive protein (hsCRP) is the most promising. To date, more than 20 prospective epidemiologic studies have demonstrated that hsCRP independently predicts vascular risk, 6 cohort studies have confirmed that hsCRP evaluation adds prognostic information beyond that available from the Framingham Risk Score, and 8 cohort studies have demonstrated additive prognostic value at all levels of metabolic syndrome or in the prediction of type 2 diabetes. In contrast to several other biomarkers that also reflect biological aspects of inflammation, hypofibrinolysis, and insulin resistance, hsCRP measurement is inexpensive, standardized, widely available, and has a decade-to-decade variation similar to that of cholesterol. Given the consistency of prognostic data for hsCRP and the practicality of its use in outpatient clinical settings, we believe the time has come for a careful consideration of adding hsCRP as a clinical criterion for metabolic syndrome and for the creation of an hsCRP-modified coronary risk score useful for global risk prediction in both men and women. Toward this end, we believe experts in the fields of epidemiology, prevention, vascular biology, and clinical cardiology should be convened to begin discussing the merits of this proposal.

Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers.

Circulating endothelial progenitor cells (EPCs) contribute to postnatal angiogenesis. The number of circulating EPCs has an inverse correlation with coronary risk scores. However, the effect of smoking on the number of circulating EPCs is not well-known. We examined the effects of chronic smoking and of smoking cessation on EPC levels. Circulating EPCs were quantified by flow cytometry as CD45lowCD34+CD133+ (progenitor cells [PCs]) or CD45lowCD34+CD133+VEGFR2+ (EPCs) in 14 nonsmokers and in 15 smokers. All smokers quit smoking. Eight quit smoking with nicotine patch and 7 without nicotine patch. PC/EPC levels were inversely correlated with the number of cigarettes smoked. Circulating PCs/EPCs increased rapidly after cessation (P<0.0001) and decreased again after resumption of smoking to the level similar to that before cessation (P=0.0031). The magnitude of increase in EPCs was greater in light smokers than in heavy smokers. The number of circulating PCs/EPCs was reduced in chronic smokers. Smoking cessation led to a rapid restoration of PC/EPC levels. The recovery of EPC levels was greater in light smokers than in heavy smokers. The decreased number of circulating EPCs would make smokers susceptible to cardiovascular disease, and even short-time cessation of smoking may be an effective means to reduce cardiovascular risk.

Concordance evaluation of coronary risk scores: implications for cardiovascular risk screening

SUMMARYObjective: To assess the similarities and differences in predicted high-risk individuals identified by different cardiovascular risk calculation algorithmsResearch design and methods: A representative population of 10 000 individuals was modelled in a computer using baseline data from the National Health Survey for England. The effects of biological variation in each major model parameters were then applied to each hypothetical individual. The predictive capacities of 3 different risk identification systems based on computer calculation (the Framingham algorithm), or on tabular methods (the Sheffield tables and the General Rule to Enable Atheroma Treatment) were evaluated.Results: All three models predict that similar numbers would receive treatment with 2.9 and 10% receiving treatment at 30 and 15% 10 year risk thresholds, respectively. However, concordance is limited as 0.3 or 6.8% are positive on all three systems; 1.6 or 9.7% on any two calculators at the 30 and 15% thresholds, respectively. The risk groups identified by each calculator depend on the baseline assumptions in each model.Conclusion: Care needs to be taken with applying risk calculators to populations different from which they were derived. Any cardiovascular risk scoring system needs to be thoroughly evaluated against epidemiological data before it is introduced and also needs to be updated in line with changing trends in risk factors.

Traditional cardiovascular risk factors measured prior to the onset of inflammatory polyarthritis.

Cardiovascular mortality is increased in patients with seropositive inflammatory polyarthritis (IP). We tested the hypothesis that the increased risk of cardiovascular disease (CVD) can be explained by elevated traditional CVD risk factor levels in persons prior to development of IP. In a population-based, prospective nested case-control study, 25 600 people aged 45-75 yr participated in a health survey, including standard CVD risk factor assessment, between the years 1993 and 1997. There were 91 incident IP cases (one-third were seropositive at presentation) identified during follow-up to the end of July 2001. Baseline CVD risk factors in the IP cases were compared with those in two age/gender-matched controls. Current smokers had an odds ratio of 2.0 (95% CI 1.0-4.0) for IP. Other risk factors, including total and LDL cholesterol, systolic and diastolic blood pressure and obesity, did not differ significantly between cases and controls. Importantly, in combination, using a standard coronary disease risk score, these factors only had a modest association with future IP, and no association when analysis was restricted to the smaller number of cases who were seropositive. Of the traditional cardiovascular risk factors, only smoking increases CVD risk prior to the onset of IP. Therefore the increased CVD observed in these patients is likely to be a consequence of factors operating after the onset of the arthritis.

Impaired brachial artery endothelium-dependent and -independent vasodilation in men with erectile dysfunction and no other clinical cardiovascular disease

ObjectivesThe goal of this study was to determine whether patients with vascular erectile dysfunction (ED) and no other clinical cardiovascular disease have structural and functional abnormalities of other vascular beds. BackgroundIn many ED patients, vascular disease is the major underlying cause. It may be that ED is an early marker of atherosclerosis in patients without clinical cardiovascular disease. MethodsWe assessed systemic vascular structure and function in 30 patients with ED and 27 age-matched normal control (NL) subjects. We measured vascular parameters, including: 1) carotid and brachial artery diameters, intima-media thickness, compliance, and distensibility; 2) aortic pulse wave velocity; 3) coronary calcification; and 4) brachial artery endothelium-dependent and -independent vasodilation. ResultsThere were no significant differences in baseline demographics, coronary artery risk score, or lipid values between the two groups. Most structural and functional vascular parameters were similar in the ED and NL groups. Brachial artery flow-mediated vasodilation (FMD) (1.3 vs. 2.4%, p = 0.014) and vasodilation to nitroglycerin (NTG) (13.0 vs. 17.8%, p < 0.05) were significantly reduced in ED patients, compared with NL subjects. In addition, there was a significant correlation between FMD and vasodilation to NTG in ED patients (r = 0.59, p < 0.05) but not in NL subjects. ConclusionsPatients with ED but no clinical cardiovascular disease have a peripheral vascular defect in endothelium-dependent and -independent vasodilation that occurs before the development of other overt functional or structural systemic vascular disease and is independent of other traditional cardiovascular risk factors.

Relation between coronary calcium and 10-year risk scores in primary prevention patients

In 380 patients, coronary calcifications were quantified by electron beam tomography and compared with the predicted 10-year cardiovascular event risk determined by the Framingham equation, Adult Treatment Panel III tables, and the PROCAM algorithm. The correlation between the amount of calcium and the predicted cardiac event risk was low (correlation coefficient range 0.19 to 0.28). The assessment of coronary calcium may thus potentially yield information that is additive to the analysis of traditional risk factors.

Endothelial function, inflammation, and prognosis in cardiovascular disease

The vascular endothelium is an active, dynamic tissue that controls many important functions, including regulation of vascular tone and maintenance of blood circulation, fluidity, coagulation, and inflammatory responses. Cardiovascular risk factors affect many of the normal functions of the endothelium. In particular, oxidized low-density lipoprotein cholesterol initiates a series of events that begin with cell activation, endothelial dysfunction, local inflammation, and a procoagulant vascular surface. These conspire to result in plaque formation and ultimately plaque rupture and cardiovascular events. Endothelial dysfunction may be evaluated by means of invasive techniques, such as coronary artery reactivity to acetylcholine, or noninvasive techniques, such as brachial artery ultrasonography. Loss of endothelium-dependent vasodilation is a characteristic feature throughout the development of atherosclerosis, and it is independently related to future adverse cardiovascular risk. Therefore, measurement of endothelial function can possibly be used to determine risk, to triage management, and to improve outcomes. At the same time, inflammation is a crucial factor in the atherosclerotic disease process. To identify and monitor the ongoing inflammatory process, markers of inflammation such as C-reactive protein (CRP) have been studied. Scientific evidence shows that elevated plasma CRP values add to the predictive ability of other established risk factors; moreover, elevated values appear to augment the Framingham Coronary Risk Score in identifying individuals who should be considered for cardioprotective treatment programs. Interestingly, thiazolidinediones (TZDs), peroxisome proliferator-activated receptor–γ agonists that are effective in the treatment of type 2 diabetes mellitus, not only increase insulin sensitivity but can benefit endothelial function because they exhibit anti-inflammatory effects. For many individuals, including those with the metabolic syndrome and/or type 2 diabetes, endothelial dysfunction and elevated plasma CRP levels indicate increased risk of cardiovascular disease. Notably, the TZDs have been shown to reduce CRP levels and may improve endothelial function.

Predictive accuracy of the Framingham coronary risk score in British men:prospective cohort study

Objective To establish the predictive accuracy of the Framingham risk score for coronary heart disease in a representative British population.Design Prospective cohort study.Setting 24 towns in the United Kingdom.Participants 6643...

The rudimentary phase of personalised medicine: coronary risk scores.

It is not uncommon for a person to ask a physician, “should I take low-dose aspirin?” Ideally, the physician would be abreast of recent data and able to quantify, on an individual basis, the patient's absolute risk for having a major life-threatening cardiovascular disease event. The American Heart Association guidelines 1 Pearson TA Blair SN Daniels SR et al. AHA Guidelines for the primary prevention of cardiovascular disease and stroke: 2002 update. Consensus panel guide to comprehensive risk reduction for adult patients without coronary or other atherosclerotic vascular diseases. Circulation. 2002; 106: 388-391 Crossref PubMed Scopus (1610) Google Scholar suggest that low-dose aspirin be used in persons with a 10-year risk of coronary heart disease that exceeds 10%—ie, at least 1% a year. We are doing a trial of 15 000 patients in which we are testing dual antiplatelet therapy for those with a 3% or higher risk of events a year. A critical problem for individual physicians is how, beyond just knowing about the presence or absence of individual risk factors, to quickly and confidently estimate the annual risk of coronary heart disease.

Relation of C-reactive protein and other cardiovascular risk factors to penile vascular disease in men with erectile dysfunction.

Erectile dysfunction (ED) may be an early sign or symptom of cardiovascular disease (CVD). We examined the relation of traditional and emerging risk factors for CVD to the severity of penile vascular disease in men with ED and without clinical coronary artery disease (CAD). In total, 137 men with ED were evaluated for penile vascular disease severity by penile Doppler ultrasound. These men were divided into the following groups based on ultrasound results: normal, cavernous venous occlusive disease, mild arterial insufficiency, and severe arterial insufficiency. Traditional (fasting lipid panel, fasting glucose, age, BMI, smoking, Framingham coronary artery disease risk score) and emerging (C-reactive protein, Lp(a), homocysteine) risk factors for CVD were correlated to severity of penile vascular disease in men with ED and without clinical CAD. Using univariate analysis, penile Doppler groups showed significant positive correlation to CRP (r=0.21; < or = 0.05) and age (r=0.30; < or = 0.01). For CRP, this correlation remained significant even when adjusted for age (< or = 0.05). Men displaying evidence of penile arterial disease (mild and severe arterial insufficiency) were characterized by elevated CRP levels (0.17 mg/dl) compared to men with no evidence of arterial abnormalities in the penis (0.04 mg/dl). CRP levels correlate significantly with increasing severity of penile vascular disease as measured by penile Doppler.

Communicating Risk—Coronary Risk Scores

SummaryCardiovascular disease, particularly heart attack and stroke, is the major cause of death in adults in Europe. The underlying atherosclerosis which causes cardiovascular disease is difficult to treat or reverse, and this has led to intense interest in strategies to prevent its development. The major causes of cardiovascular disease—a high fat diet, tobacco smoking and high blood pressure—are now well known. Control of these risk factors has been shown to reduce the risk of heart attack or stroke. It is now possible with simple information (age, sex, blood pressure level, cholesterol level and information on smoking) to predict the risk of heart attack or stroke fairly accurately. The challenge for the future is to make the information available on risk prediction and on how to reduce risk accessible to lay people, so that they may choose, if they wish, to adopt a life style that will reduce their risk. Such a life style involves healthy food choices, avoidance of overweight, the promotion of leisure exercise and complete avoidance of tobacco. Drug treatments can be extremely effective in controlling both blood pressure and cholesterol levels, but they should be seen as an adjunct to life style measures rather than a primary means of achieving prevention. Practical prevention will only be achieved through dynamic partnerships between the medical profession, Government, voluntary bodies, teaching institutions, insurance companies and paramedical bodies. An outline about how cardiac societies can participate in this process is appended.

2P-0318 Concordance evaluation of coronary risk scores — Implications for CHD risk screening

2P-0318 Concordance evaluation of coronary risk scores — Implications for CHD risk screening

Age and sex distribution of subclinical aortic atherosclerosis: a magnetic resonance imaging examination of the Framingham Heart Study.

Autopsy data demonstrate a correlation between subclinical aortic atherosclerosis and cardiovascular disease. Therefore, noninvasive cardiovascular magnetic resonance (CMR) of subclinical atherosclerosis may provide a novel measure of cardiovascular risk, but it has not been applied to an asymptomatic population-based cohort to establish age- and sex-specific normative data. Participants in the Framingham Heart Study offspring cohort who were free of clinically apparent coronary disease were randomly sampled from strata of sex, quartiles of age, and quintiles of Framingham Coronary Risk Score. Subjects (n=318, aged 60+/-9 years, range 36 to 78 years, 51% women) underwent ECG-gated T2-weighted black-blood thoracoabdominal aortic CMR scanning. CMR evidence of aortic atherosclerosis was noted in 38% of the women and 41% of the men. Plaque prevalence and all measures of plaque burden increased with age group and were greater in the abdomen than in the thorax for both sexes and across all age groups. In addition, the Framingham Coronary Risk Score was significantly correlated with all plaque prevalence and burden measures for women but only for men after age adjustment. These noninvasive CMR data extend the prior autopsy-based prevalence estimates of subclinical atherosclerosis and may help to lay the foundation for future studies of risk stratification and treatment of affected individuals.

Quantification of coronary risk score.

To quantify the coronary risk score in children and/or grandchildren of patients with coronary artery disease (CAD). One hundred and fifty children with positive family history of CAD (cases) and age and sex matched children with no such history (controls) were enrolled in the study. Fasting blood sugar, serum cholesterol and triglycerides were estimated on all children and a risk score was calculated using Nora's scheme. The cases and controls were similar with respect to mean age, six distribution, mean weight and mean height. None of the child was hypertensive. Mean serum levels of triglycerides were 164.7 m/dl and 105.7 mg% respectively in cases and controls (p < 0.005). Prevalence of hypertriglyceridemia was three times more in cases (p < 0.001). Cases had a significantly higher risk scores (p < 0.00001) and this was mainly attributable to higher biochemical risk (P < 0.0006). Children and grand children with a positive family history of CAD had significantly higher risk scores for future CAD. The increased risk was mainly due to biochemical derangements.

Cumulative Effects of Cholesterol and other Risk Factors on Coronary Artery Calcification in Men and Women:

P92 Introduction: Coronary artery calcification (CAC) by electron beam computed tomography (EBCT) is associated with contemporaneous levels of traditional risk factors (RFs). The availability of repeated measures over 25 years allows a unique examination of relations of CAC with long-term RF levels in Framingham Heart Study subjects. Methods: Men and women free of symptomatic coronary disease underwent EBCT. Subjects were randomly sampled across quartiles of age and quintiles of Framingham coronary risk score. Longterm RFs were derived from 25-year averaged values. Logistic regression was used to relate long-term RFs to CAC. Results: In 167 men (35-76 yrs) and 160 women (35-77 yrs), age, long-term total cholesterol, and long-term systolic BP were related to Agatston CAC score ≥ 100 ( Table). In multivariable analyses, long-term total cholesterol was an independent predictor of CAC (p&lt;0.02). Conclusion: Long-term exposure to coronary disease RFs is associated with increased risk for subclinical CAC. These studies may provide insights into differences in RFs for clinical coronary events and for atherosclerosis. Table 1.

Body mass index and metabolic risk factors for coronary heart disease in women.

Prospective epidemiological studies demonstrate an increase in coronary heart disease mortality in women beginning at values of body mass index > or = 22 kg. m(-2). However, the metabolic basis for this observation has not been adequately studied in women. Our aim was to examine the association between body mass index, metabolic coronary heart disease risk factors and a predicted 10-year coronary heart disease risk score in a large occupational cohort of women in the U.K. We carried out a cross-sectional survey of cardiovascular risk factors in 14 077 women, aged 30-64 years. The main outcome measures were systolic and diastolic blood pressure, serum total cholesterol, HDL cholesterol, total cholesterol/HDL cholesterol ratio, LDL-cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein(a), fasting blood glucose and a predicted 10-year coronary risk score. Across seven categories of body mass index, i.e. < 20, 20-, 22-, 24-, 26-, 28- and > or = 30 kg. m(-2), there were highly significant age-adjusted increases in the risk factors (all P < 0.001), except for a decrease in HDL cholesterol and ApoA1 (all P<0.001) and no relationship with lipoprotein(a) (P = 0.05). Based on a multifactorial 10-year coronary heart disease risk estimate, odds ratios for being in the highest quintile of risk for each category of body mass index, were 1 (< 20 kg. m(-2)), 0.91, 1.56, 2.18, 2.97, 3.83 and 4.21 (> or = 30 kg. m(-2)). The significant rise in metabolic coronary heart disease risk at 22 kg. m(-2)observed in this study is consistent with prospective epidemiological studies in women which have reported an increase in coronary heart disease mortality starting at 22 kg. m(-2). However, body mass index was a poor discriminator of women at different levels of coronary heart disease risk. The primary goal of weight loss in individuals should be the correction of dysmetabolism, irrespective of the level of body mass index.