High-sensitivity C-reactive protein: a novel and promising marker of coronary heart disease

BACKGROUND: Coronary heart disease remains the leading cause of morbidity and mortality in the industrialized world. Clinical and laboratory studies have shown that inflammation plays a major role in the initiation, progression, and destabilization of atheromas. C-Reactive protein (CRP), an acute phase reactant that reflects low-grade systemic inflammation, has been studied in a variety of cardiovascular diseases. APPROACH: Findings from prospective clinical trials were examined to determine the prognostic utility of CRP in acute coronary syndromes, and observations from epidemiological studies were reviewed to determine the ability of CRP to predict future first coronary events. The analytical considerations of CRP measurement in these clinical applications were also examined. CONTENT: In patients with established coronary disease, CRP has been shown to predict adverse clinical events. In addition, prospective studies have consistently shown that CRP is a strong predictor of future coronary events in apparently healthy men and women. The relative risk associated with CRP is independent of other cardiovascular disease risk factors. High-sensitivity CRP (hs-CRP) assays are needed for risk assessment of cardiovascular disease. Such assays are currently available but may require further standardization because patients' results will be interpreted using population-based cutpoints. Preventive therapies to attenuate coronary risk in individuals with increased hs-CRP concentrations include aspirin and statin-type drugs. SUMMARY: hs-CRP has prognostic utility in patients with acute coronary syndromes and is a strong independent predictor of future coronary events in apparently healthy subjects.     

Novel HDL-based therapeutic agents

Reduction in low-density lipoprotein cholesterol (LDL-C) levels has been associated with a 25-30% reduction in cardiovascular disease risk. However, there still remains a significant and quantifiable risk. Since epidemiologic data have demonstrated that low levels of high-density lipoprotein cholesterol (HDL-C) are associated with an increased risk for cardiovascular disease, novel therapeutic agents are currently being developed to either raise HDL-C levels or enhance HDL functionality. This review will highlight some of these therapeutic agents including cholesteryl ester transfer protein inhibitors, apolipoprotein A-I mimetics, RVX-208, and apolipoprotein A-I based infusion therapies. For each therapeutic class, an overview of the mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be provided.     

系统性红斑狼疮患者血清超敏C反应蛋白水平与心血管危险因素的关系

目的在系统性红斑狼疮患者中分析超敏C反应蛋白（hs-CRP）与心血管危险因素的关系。方法收集200例系统性红斑狼疮患者的一般资料,包括：、性别、年龄、病程、身高、体重和血压;检测血清hs-CRP、血清总胆固醇、甘油三酯、C3、C4~ESR;计算体重指数和sLE疾病活动指数（SLEDAI）。结果hs-CRPTk平与sLEDAI及补体c3、c4之间无明显相关（P〉0．05）,而与病程、BMI、血压、血清总胆固醇、甘油三酯、CI冲和EsR之间呈正相关（P〈0．05）。结论研究表明：在SLE患者中检测hs．CRP的水平尽管不能作为疾病活动的标志,但能够用于评估其心血管风险。     

Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults

BACKGROUND: Increased concentrations of high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, are associated with increased risk for coronary heart disease. Because of its relationship to inflammation, hs-CRP has considerable biologic variation. This study was carried out to characterize CRP variation and to compare it to another risk factor, total serum cholesterol. METHODS: One hundred thirteen individuals were scheduled to have five measurements each of hs-CRP and total cholesterol carried out at quarterly intervals over a 1-year period. Variations of hs-CRP and total cholesterol were characterized, and classification accuracy was described and compared for both. RESULTS: The relative variation was comparable for hs-CRP and total cholesterol. When classified by quartile, 63% of first and second hs-CRP measurements were in agreement; for total cholesterol it was 60%. Ninety percent of hs-CRP measurements were within one quartile of each other. This relationship was not altered by the use of log-transformed hs-CRP data. CONCLUSION: hs-CRP has a degree of measurement stability that is similar to that of total cholesterol.     

Vascular stiffness in familial hypercholesterolaemia is associated with C-reactive protein and cholesterol burden

BACKGROUND: Familial hypercholesterolaemia (FH) is characterized by very high serum cholesterol and premature coronary atherosclerosis. Arterial stiffness and atherosclerosis are two major underlying pathophysiologies of arterial disease that are predictive of future cardiovascular events. The aims of this study were to quantify atherosclerosis and arterial stiffness and to evaluate their relationship with high sensitive C-reactive protein (hs-CRP) and the level of exposure to high serum cholesterol in FH patients. Materials AND METHODS: We measured traditional risk factors, hs-CRP, intima-media thickness (IMT) of carotid artery, and brachial-ankle pulse wave velocity (baPWV) in 35 heterozygous FH subjects and 17 healthy control subjects. Cholesterol-year score (CYS) was calculated to estimate the lifetime cholesterol burden in FH subjects. RESULTS: FH subjects had significantly elevated total cholesterol, low-density lipoprotein cholesterol, and carotid IMT compared with those without mutations. Among FH patients, the baPWV and carotid IMT were higher in cases with high cholesterol burden than those without. Similarly, the baPWV and carotid IMT were also higher in cases with elevated hs-CRP (> 1 mg L(-1)) than those without. Multiple linear regression analysis demonstrated CYS and hs-CRP were significant independent predictors of baPWV and IMT in FH patients. CONCLUSIONS: Both high cholesterol burden and vascular inflammation are not only associated with atherosclerosis, but also contribute to the development of arterial stiffness in FH patients. Early detection of hypercholesterolaemia in FH patients is warranted to prevent the untoward pathophysiologies.     

Opening a new lipid "apo-thecary": incorporating apolipoproteins as potential risk factors and treatment targets to reduce cardiovascular risk

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) represent the cornerstone of drug therapy to reduce low-density lipoprotein (LDL) cholesterol and cardiovascular risk. However, even optimal statin management of LDL cholesterol leaves many patients with residual cardiovascular risk, in part because statins are more effective in reducing LDL cholesterol than apolipoprotein B (Apo B). Apo B may be a better marker of atherogenic risk than LDL cholesterol because Apo B measures the total number of all atherogenic particles (total atherosclerotic burden), including LDL, very low-density lipoprotein, intermediate-density lipoprotein, remnant lipoproteins, and lipoprotein(a). To determine whether Apo B is a better indicator of baseline cardiovascular risk and residual risk after lipid therapy compared with LDL cholesterol, a MEDLINE search of the literature published in English from January 1, 1975, through December 1, 2010, was conducted. On the basis of data from most population studies, elevated Apo B was more strongly associated with incident coronary heart disease than similarly elevated LDL cholesterol. Apo B was also a superior benchmark (vs LDL cholesterol) of statins' cardioprotective efficacy in both primary-prevention and secondary-prevention trials. To minimize cardiovascular risk among persons with hypercholesterolemia or dyslipidemia, the best available evidence suggests that intensive therapy with statins should be initiated to achieve the lowest possible Apo B level (with adequate drug toleration) and then other therapies (eg, niacin, bile acid resins, ezetimibe) added to potentiate these Apo B-lowering effects. In future consensus lipid-lowering treatment guidelines, Apo B should be considered as an index of residual risk, a potential parameter of treatment efficacy, and a treatment target to minimize risk of coronary heart disease.     

C-reactive protein and high-sensitivity C-reactive protein: an update for clinicians

The measurement of C-reactive protein (CRP) using both standard and high-sensitivity CRP (hs-CRP) assays is becoming common in clinical practice. This article addresses the causes of CRP elevation and the use of different CRP assays in internal medicine, including cardiology, gastroenterology, rheumatology, infectious diseases, and oncology. We focus on the recent medical literature on the use of hs-CRP in cardiovascular disease risk stratification and management, including updated screening guidelines on the use of hs-CRP, such as those issued in 2009 by the Canadian Cardiovascular Society. We also discuss the Reynolds Risk Score, which incorporates hs-CRP and family history with more standard cardiovascular risk factors (eg, tobacco use, hypertension, and dyslipidemia) and frequently leads to improved recategorization of cardiovascular disease risk levels. As the recently completed Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial indicated that statin therapy decreases the vascular events among persons with elevated hs-CRP by half, even when cholesterol levels are low, the inclusion of information on hs-CRP values with other cardiovascular risk factors may assist physicians in medical decision making for patients.     

The effect of fenofibrate on the levels of high sensitivity C-reactive protein in dyslipidaemic hypertensive patients

It is now well documented that hypertension is associated with a chronic low-grade inflammatory state. Levels of high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation and a mediator of atherothrombotic disease, have been shown to correlate with cardiovascular disease risk. Our objective was to evaluate the effect of fenofibrate on the levels of hs-CRP in dyslipidaemic hypertensive patients. We selected 30 dyslipidaemic hypertensive patients and 20 normolipidemic normotensive healthy subjects. Dyslipidaemic hypertensive patients were treated with fenofibrate 200 mg/day for 3 months. Serum hs-CRP and metabolic parameters were evaluated at baseline in both groups and after fenofibrate treatment in dyslipidaemic hypertensive patients. At baseline, significantly higher hs-CRP levels were found in dyslipidaemic hypertensive patients than normal subjects (0.48 +/- 0.3 vs. 0.15 +/- 0.1 mg/dl, p < 0.01). Total cholesterol, low-density lipoprotein cholesterol and triglyceride significantly decreased (p < 0.05, p < 0.05 and p < 0.01, respectively), and levels of high-density lipoprotein cholesterol significantly increased (p < 0.05) after treatment with fenofibrate in dyslipidaemic hypertensive group. Levels of hs-CRP significantly decreased after fenofibrate treatment from a mean of 0.48 +/- 0.3 mg/dl to vs. 0.16 +/- 0.2 mg/dl, p < 0.01). Our findings suggest that fenofibrate may be used as a first-line therapy for improving the plasma lipids profile as well as the chronic low-grade inflammatory state in dyslipidaemia and hypertension.     

The effect of thyroid disorders on lipid levels and metabolism

Thyroid hormones regulate cholesterol and lipoprotein metabolism, whereas thyroid disorders, including overt and subclinical hypothyroidism, considerably alter lipid profile and promote cardiovascular disease. Good evidence shows that high thyroid-stimulating hormone (TSH) is associated with a nonfavorable lipid profile, although TSH has no cutoff threshold for its association with lipids. Thyromimetics represent a new class of hypolipidemic drugs: their imminent application in patients with severe dyslipidemias, combined or not with statins, will improve the lipid profile, potentially accelerate energy expenditure and, as a consequence, vitally lessen the risk of cardiovascular disease.     

The significance of cardiovascular risk factors and C-reactive protein to the development of atherosclerosis in women with systemic lupus erythematosus

Compared with general population, women suffering from systemic lupus erythematosus (SLE) have signs of coronary artery disease (CAD) five to eight times more often, especially in young age. Early development of atherosclerosis in patients with SLE is caused by conventional cardiovascular risk factors and specific ones, associated with the disease and its therapy. A slight increase in such an inflammatory marker as C-reactive protein (CRP) is thought to reflect the presence of subclinical inflammation in the vascular wall, connected with atherosclerotic process. The authors analyzed the frequency of clinical and subclinical (an increase in the thickness of intima-media complex (IMC)) atherosclerotic manifestations, the summary coronary risk, the prevalence of conventional risk factors, and CRP level in 133 female patients with SLE and in 50 healthy donors. Compared to the control group, SLE patients were younger, developed cardiovascular diseases (CAD, stenocardia, myocardial infarction, and cerebral stroke (p = 0.05) as well as arterial hypertension more often, had higher levels of hs-CRP and triglycerides, and lower levels of high density lipoprotein cholesterol (HDLC). There was a positive correlation between hs-CRP level and the activity of the disease according to ECLAM score, ES value, IgG and IgM levels, hematological disturbances (anemia, leucopenia, and/or thrombocytopenia) , and a negative correlation with total cholesterol level, HDLC there was a moderate correlation between hs-CRP and a maximal IMC value.