C-reactive protein and cardiovascular disease: Weighing the evidence

C-reactive protein (CRP) has been widely promoted as a strong, independent predictor of cardiovascular events and metabolic syndrome, both in general populations and in patients with clinical cardiovascular disease, and as a causal player in atherothrombosis. However, recent evidence shows that the association of CRP with cardiovascular events is weaker than previously thought, that it may be largely attributed to confounding by established causal risk factors, and that CRP is, therefore, probably not a clinically useful risk predictor. The lack of association of non-coding CRP gene polymorphisms (which determine different baseline CRP values) with coronary events or metabolic syndrome does not support a causal role for CRP, and most of the putatively proatherothrombotic in vitro effects claimed for CRP were caused by contaminants in commercial CRP preparations and not by CRP. Future clinical trials of specific CRP inhibitors now in development could directly test the contribution of CRP to pathogenesis of cardiovascular disease.     

C-reactive protein and risk of cardiovascular disease: Evidence and clinical application

Prospective epidemiologic data consistently show that elevated C-reactive protein (CRP) levels are associated with an increased risk of subsequent cardiovascular events in apparently healthy populations, and accumulating laboratory research is uncovering possible mechanisms by which CRP may influence the development of atherothrombotic disease. CRP is a stronger predictor of cardiovascular disease than is low-density lipoprotein (LDL) cholesterol. CRP adds prognostic information at all levels of the calculated Framingham risk score and at all levels of severity of the metabolic syndrome. Commercially available high-sensitivity assays suitable for use in clinical settings allow for the routine assessment of CRP as a useful adjunct in cardiovascular risk screening. When such assays are used, CRP levels of less than 1, 1 to 3, and greater than 3 mg/L differentiate patients at low, moderate, and high risk, respectively, for future cardiovascular events. Persons with high CRP but normal LDL cholesterol comprise a high-risk group frequently overlooked in clinical practice. Knowledge of their high-risk status may improve these patients’ compliance with recommended lifestyle changes that are likely to improve prognosis. Preliminary data suggest that individuals with elevated CRP but low LDL cholesterol may benefit from pharmacologic interventions, including statin therapy. Large-scale trials are underway to assess the net efficacy and public health impact of this approach to the primary prevention of myocardial infarction and stroke.     

High-sensitivity C-reactive protein as a risk assessment tool for cardiovascular disease

Almost half of first cardiovascular events occur in individuals with no known risk factors. Attempts in the last decade to predict cardiovascular risk more accurately have led to the emergence of a novel risk factor, C-reactive protein (CRP), which has proved to be as good a risk predictor as low-density lipoprotein cholesterol. C-reactive protein is an index of inflammation that is now believed to promote directly all stages of atherosclerosis, including plaque rupture. As measured by high-sensitivity assays, high-sensitivity CRP (hs-CRP) also independently predicts recurrent events in patients with known coronary artery diseases. Recent evidence implicates hs-CRP, and thus inflammation, in the metabolic syndrome and diabetes mellitus, particularly in women. As a clinical tool for cardiovascular risk assessment, hs-CRP testing enhances information provided by lipid screening or global risk assessment. Statin therapy and other interventions can lower hs-CRP. Whether or not such reductions can prevent cardiovascular events is under investigation.     

Elevated sialic acid, but not CRP, predicts features of the metabolic syndrome independently of BMI in women

AIMS: C-reactive protein (CRP) is a predictor of many diseases including type II diabetes and cardiovascular disease. Fewer studies have similarly shown sialic acid (SA) to be a predictor of obesity-related diseases, but importantly SA shows less intra-individual variability than CRP and acts as an integrated marker of the activity of a number of acute-phase proteins. This study examines the association between both CRP and SA with individual and combined features of the metabolic syndrome. SUBJECTS: In all, 257 women with a body mass index (BMI) ranging from 25.1 to 54.5 kg/m2 (geometric mean 33.1+/-5.8 kg/m2) and aged 19-71 y (mean 45.6+/-12.1 y) were studied. Subjects had no symptoms of intercurrent infection, known diabetes, treated dyslipidaemia, a chronic inflammatory condition, liver disease or malignancy. RESULTS: Linear regression demonstrates that both CRP and SA were positively associated with weight, BMI, insulin resistance, dyslipidaemia and hypertension. There was a highly significant (P<0.0001) positive association of both SA and CRP with none, one, two, three or four features of the metabolic syndrome. For a 1 s.d. (4.0 mg/l) increase in CRP, there was a significant increased risk when comparing the odds of having metabolic syndrome (defined as three or more individual features) compared with the remainder of the population (odds ratio=1.7, P<0.0001), but this was not significant after adjustment for BMI. However, for a 1 s.d. (0.34 mmol/l) increase in SA, the odds of having metabolic syndrome compared with those without metabolic syndrome was 2.5 (P<0.0001), and persisted after additional adjustment for BMI (adjusted odds ratio=1.9, P<0.0001). CONCLUSIONS: While SA and CRP are both univariately associated with individual features of the metabolic syndrome, SA, but not CRP, is significantly associated with the metabolic syndrome, independent of BMI. We conclude that SA identifies a subgroup of overweight individuals with an inflammatory phenotype, who are at the greatest risk of metabolic syndrome.     

Markers of inflammation and prevalence of vascular disease in patients with metabolic syndrome.

AIM: The aim of this study was to determine the prevalence of carotid atherosclerosis and coronary heart disease and cerebrovascular disease in subjects with metabolic syndrome and to investigate the relationship between atherosclerosis and C-reactive protein (CRP) levels. METHODS: We studied 568 ambulatory subjects, referred to our Center for the study of atherosclerosis and cardiovascular prevention by general practitioner, for the presence of traditional cardiovascular risk factors. Subjects were divided in two groups: those with metabolic syndrome (n=163), and those with 0-2 metabolic abnormalities (n=405). All subjects underwent carotid artery ultrasound and blood tests including high sensitivity-CRP measurement. RESULTS: Prevalence of carotid lesions, previous cardiac or cerebrovascular events was higher in patients with metabolic syndrome. CRP levels were higher in patients with metabolic syndrome (0.6+/-0.23 vs 0.42+/-0.2, P<0.01). An increased relative risk for carotid atherosclerosis, coronary heart disease and cerebrovascular disease was not associated with each single component of the metabolic syndrome, but it was significantly associated with the coexistence of three or more of these. Patients with the metabolic syndrome had a higher incidence of carotid and coronary disease, if CRP levels were above 0.3 mg/dL. CONCLUSION: Patients with metabolic syndrome are at increased risk for cardiovascular events. Strategy to treat these patients is not well clarified. Life style changes are mandatory, but in very high-risk subgroups secondary prevention strategies may be advisable. These may be identified by using CRP levels as a marker.     

C-reactive protein is a strong independent predictor of death in type 2 diabetes: association with multiple facets of the metabolic syndrome.

INTRODUCTION: It has been suggested that atherosclerotic vascular disease is a chronic inflammatory process. The aim of this study was to investigate the importance of C-reactive protein (CRP) as a cardiovascular risk marker and predictor of death, as well as its relation to other factors of the metabolic syndrome in a cohort of type 2 diabetic patients at high risk of severe macrovascular complications. MATERIAL AND METHODS: 592 patients, aged 55 to 74 years (311 men, 281 women), with signs and symptoms of circulation deficits were examined by duplex ultrasound for suspected cerebrovascular and peripheral arterial disease and followed over a period of 5 years. At baseline, 292 patients of the total group had type 2 diabetes (49.3%). Ischemic heart disease was present in 40.2%, internal carotid stenosis in 21.9% and peripheral arterial disease in 39.7% of the subjects. RESULTS: During the observation period, 104 patients had died, 72 (69.2%) due to cardiovascular causes. Non-fatal myocardial infarction occurred in 39 patients (7.4%), non-fatal stroke in 70 patients (13.3%) and amputations because of gangrene were unavoidable in 24 patients (4.6%). In Cox regression analysis, CRP was the strongest predictor of death and cardiovascular death in the total cohort (RR 3.7 [95% CI 1.86-7.50] and 5.4 [2.13-13.76]), as well as in the type 2 diabetic subgroup (RR 3.3 [1.27-8.70] and 5.4 [1.44-20.0]). In contrast neither the traditional cardiovascular risk factors nor the data of diabetic metabolic control were able to improve prediction. CRP was correlated positively with plasma levels of triglycerides (r=0.19, p=0.002), C-peptide (r=0.21, p=0.004), postprandial glucose (r=0.17, p=0.009), albuminuria (r=0.16, p=0.020), and inversely with HDL cholesterol (r=-0.20, p=0.002) in type 2 diabetic patients. CONCLUSIONS: CRP seems to be a better predictor of death and cardiovascular events than traditional risk factors or parameters of metabolic control in type 2 diabetic patients at high risk for cardiovascular endpoints. Additionally, CRP is associated with several facets of the metabolic syndrome.     

Markers of inflammation, metabolic risk factors, and incident heart failure in American Indians: the Strong Heart Study

Inflammation may play a role in increased risk of heart failure (HF) that is associated with obesity, metabolic syndrome (MS), and diabetes. This study investigated associations between inflammatory markers, MS, and incident HF in a population with a high prevalence of diabetes, obesity, and MS. The cohort consisted of 3098 American Indians without prevalent cardiovascular disease who had C-reactive protein (CRP) and fibrinogen measured at the Strong Heart Study phase II examination. Independent associations between inflammatory markers, MS, and HF were analyzed by Cox hazard models. During a mean follow-up of 11 years, 218 participants developed HF. After the adjustment for cardiovascular risk factors, fibrinogen, (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.15-1.59) but not CRP (HR, 1.25; 95% CI, 0.97-1.32) remained a significant HF predictor. In individuals without diabetes, concomitant presence of MS and elevated CRP or fibrinogen increased HF risk (for MS and CRP: HR, 2.02; 95% CI, 0.95-4.31; for CRP and fibrinogen: HR, 1.75; 95% CI, 0.83-3.72). In a population with a high prevalence of obesity, MS, and diabetes, elevated CRP and fibrinogen increased HF risk. These associations are attenuated by the adjustments for conventional risk factors suggesting that inflammation acts in concert with metabolic and clinical risk factors in increasing HF risk.     

Untangling the heavy cardiovascular burden of obesity

This article sets out the clinical context of the research presented by Romero-Corral et al. in an accompanying article in this journal. Obesity is an important risk factor for the development of cardiovascular disease. Among other metabolic abnormalities, obesity is associated with elevated levels of the inflammatory biomarker C-reactive protein (CRP) and of leptin. Here, we discuss the study carried out by Romero-Corral and colleagues-an analysis of leptin, CRP and cardiovascular risk factors. These researchers found that raised leptin concentrations were a more robust predictor of cardiovascular events than CRP; the highest risk was observed in participants with raised concentrations of both markers. We explore the possible mechanism for this interaction, and propose that leptin's stimulatory effect on the sympathetic nervous system and its ability to impair baroreceptor control might be involved.     

Plasma procalcitonin and the risk of cardiovascular events and death: a prospective population‐based study

Abstract. Schiopu A, Hedblad B, Engström G, Struck J, Morgenthaler NG, Melander O (Lund University, Skåne University Hospital Malmö, Malmö, Sweden; BRAHMS GmbH/Thermo Fisher Scientific, Hennigsdorf, Germany). Plasma procalcitonin and the risk of cardiovascular events and death: a prospective population‐based study. J Intern Med 2012; 272: 484–491. Objectives: A number of inflammatory biomarkers such as C‐reactive protein (CRP) are independent predictors of cardiovascular risk. The inflammatory biomarker procalcitonin (PCT) has previously been shown to be associated with coronary atherosclerosis and the metabolic syndrome. We evaluated the ability of PCT to predict future cardiovascular events in a population of apparently healthy individuals. Design: We measured plasma PCT levels in 3713 subjects with no previous history of cardiovascular disease, randomly selected from the Malmö Diet and Cancer cohort. The correlation between PCT concentration and the incidence of coronary events, stroke and cardiovascular death over a median follow‐up period of 13.7 years was studied using a Cox regression analysis corrected for age, sex, CRP level, traditional risk factors and renal function. Results: Age and sex were strong determinants of PCT; the concentration of PCT was significantly higher in men than in women. PCT was associated with several of the established cardiovascular risk factors (CRP, hypertension, diabetes and renal function) as determined by multivariate linear regression. Of note, PCT was inversely correlated with HDL and smoking. We found significant correlations between PCT levels, coronary events and cardiovascular death. However, these relationships lost statistical significance when the analysis was corrected for CRP and the traditional risk factors. Conclusions: This is the largest population‐based prospective study to demonstrate a positive association between plasma PCT levels and cardiovascular risk in subjects with no previous history of acute cardiovascular events. However, the high degree of covariation between PCT and other cardiovascular risk factors limits the value of PCT as an independent cardiovascular risk predictor.     

Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease

The polycystic ovary syndrome (PCOS), one of the most common reproductive abnormalities, shares some components of the metabolic cardiovascular syndrome. Therefore, PCOS patients may represent the largest group of women at high risk for the development of early-onset cardiovascular disease (CVD) and/or diabetes. C-reactive protein (CRP) is a strong independent predictor of future CVD and/or stroke. Only one small published study has looked for such an association (17 PCOS patients vs. 15 controls). The objective of this study was to compare the levels of CRP and other risk factors of CVD in a large group of PCOS patients and controls. CRP measurements were undertaken in 116 PCOS patients and 94 body mass index-matched controls with regular menstrual cycles. Whereas 36.8% of the PCOS patients had CRP levels above 5 mg/liter, only 9.6% of the controls exhibited high CRP levels (P < 0.001). The mean +/- SD was 5.46 +/- 7.0 in the PCOS group vs. 2.04 +/- 1.9 mg/liter in the control (P < 0.001). The body mass index, white blood cell count, TSH, glucose, cholesterol, and homocysteine levels were not significantly different between the two groups. CRP levels are elevated in patients with PCOS and may be a marker of early cardiovascular risk in these patients. High CRP levels may explain why some PCOS women may possibly be at an increased risk for the development of early-onset CVD. Consequently, whether treatment regimens directed toward lowering CVD risk factors should be more aggressive for those PCOS women with increased CRP levels, awaits further clinical experience.     

Insulin resistance is a cardiovascular risk factor in humans

Diabetes is a common metabolic disorder associated to elevated cardiovascular morbidity and mortality that is not explained by hyperglycemia or traditional cardiovascular risk factors such as smoking or hypercholesterolemia. Intensive glycemic control with insulin that achieves near-normal glycemia does not reduce significantly macrovascular complications compared with conventional glycemic control. Cardiovascular disease continues to develop in patients with diabetes despite adequate glycemic control. In contrast, intensive control with metformin (leading to insulin resistance improvement) reduces diabetes complications, including cardiovascular events, suggesting that enhancement of insulin sensitivity rather than plasma glucose level has a major role improving diabetes outcomes. Accordingly, insulin resistance estimated by glucose tolerance tests is better predictor of future cardiovascular events than fasting glucose level in nondiabetic individuals. Insulin resistance precedes for decades the clinical onset of type 2 diabetes and deteriorates metabolic control of type 1 diabetes. Numerous investigations including cross-sectional and prospective studies, meta-analyses, and systematic reviews provide compelling evidence that insulin resistance by itself is a cardiovascular risk factor in a variety of population groups, including the general population and patients with diabetes. Several estimations of insulin resistance have been consistently associated with elevated rate of cardiovascular events independently of other cardiovascular risk factors and diabetes status. The clinical expression of insulin resistance (the metabolic syndrome or any of its components including obesity, hyperinsulinemia, hypertension, and dyslipemia) has been related to cardiovascular disease as well. An estimation conducted by the Archimedes model confirms that insulin resistance is the most important single cause of coronary artery disease.     

High-sensitivity C-reactive protein in patients with metabolic syndrome

High-sensitivity C-reactive protein (CRP) has been shown to predict cardiovascular disease. Metabolic syndrome has been found to play a critical role in the development of cardiovascular disease. The purpose of this report is to assess the relationship between CRP and the metabolic syndrome. A total of 50 patients with metabolic syndrome and 40 healthy persons were included in the study. Plasma concentrations of CRP were measured by means of particle-enhanced immunonephelometry with the Behring nephelometer using N Latex CRP mono reagent. CRP levels were higher in patients with metabolic syndrome than control group (10.6 +/-5.4 mg/L vs 3.5 +/-0.8 mg/L, p<0.001). In partial correlation, plasma CRP positively correlated with body mass index (p<0.001), waist circumference (p<0.001), waist-to-hip ratio (p<0.01), total cholesterol (p<0.001), LDL-cholesterol (p=0.033), triglyceride (p=0.023), and fasting blood glucose (p=0.043) in patients with metabolic syndrome. HDL-cholesterol did not significantly correlate with CRP (p>0.05). In multiple regression analysis, body mass index (p<0.01), waist circumference (p<0.01), and fasting blood glucose (p<0.01) showed independent correlations with plasma CRP. CRP levels were found higher in patients with metabolic syndrome. These results suggest that abdominal obesity is the critical correlates of elevated plasma CRP levels found in patients with metabolic syndrome. These patients carrying high risk for cardiovascular events must be followed closely.     

Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study

BACKGROUND: Despite abundant epidemiologic evidence, the role of elevated serum uric acid level as a cardiovascular risk factor is controversial. We assessed the predictive value of serum uric acid levels for cardiovascular and overall mortality. METHODS: A population-based prospective cohort study was performed of 1423 middle-aged Finnish men initially without cardiovascular disease, cancer, or diabetes. The main outcome measure was death from cardiovascular disease and any cause. RESULTS: The mean follow-up was 11.9 years. There were 157 deaths during follow-up, of which 55 were cardiovascular. In age-adjusted analyses, serum uric acid levels in the upper third were associated with a greater than 2.5-fold higher risk of death from cardiovascular disease than levels in the lower third. Taking into account cardiovascular risk factors and variables commonly associated with gout increased the relative risk to 3.73. Further adjustment for factors related to the metabolic syndrome strengthened the risk to 4.77. Excluding the 53 men using diuretics did not alter the results. In age-adjusted analyses, men with serum uric acid levels in the upper third were 1.7-fold more likely to die of any cause than men with levels in the lower third. Adjustment for further risk factors strengthened the association somewhat. CONCLUSIONS: Serum uric acid levels are a strong predictor of cardiovascular disease mortality in healthy middle-aged men, independent of variables commonly associated with gout or the metabolic syndrome. Serum uric acid measurement is an easily available and inexpensive risk marker, but whether its relationship to cardiovascular events is circumstantial or causal remains to be answered.     

Oxidative Stress and Inflammation as Predictors of Mortality and Cardiovascular Events in Hemodialysis Patients: The DREAM Cohort

Aim: Both oxidative stress and inflammation are involved in the pathogenesis of cardiovascular disease (CVD). The serum level of derivatives of reactive oxygen metabolites (d-ROMs) is a measure of the total amount of hydroperoxides serving as a marker of oxidative stress. We investigated whether d-ROMs could predict the clinical outcomes in hemodialysis patients and whether the associations of d-ROMs with the outcomes are independent of a marker of inflammation, C-reactive protein (CRP).Methods: This was a prospective cohort study in hemodialysis patients. The key exposures were the serum levels of d-ROMs and CRP. The outcome measures were all-cause mortality and new CVD events.Results: A total of 517 patients were analyzed. d-ROMs correlated positively with CRP. During follow-up for 5 years, 107 patients died, and 190 patients experienced new CVD events. In the Kaplan–Meier analyses, both higher d-ROMs and higher CRP levels predicted higher risks for mortality and CVD events. By Cox proportional-hazard regression analysis adjusted for potential confounders excluding CRP, d-ROMs exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for CRP. Using the same model, CRP exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for d-ROMs. When we analyzed new CVD events as the outcome, CRP was a significant predictor, whereas the level of d-ROMs was not.Conclusions: Although d-ROMs predicted mortality and CVD events in unadjusted models, the associations of d-ROMs with these outcomes were not independent of CRP. Oxidative stress and inflammation appear to share common causal pathways.     

Statin Therapy in Metabolic Syndrome and Hypertension Post-JUPITER: What is the Value of CRP?

Much evidence supports a pivotal role for inflammation in atherosclerosis. C-reactive protein (CRP), the prototypic marker of inflammation in humans, is a cardiovascular risk marker and may also promote atherogenesis. CRP levels are increased in metabolic syndrome and hypertension and confer increased risk of cardiovascular events in patients in these subgroups. Statins have been shown to lower low-density lipoproteins and CRP independently, and reduce cardiovascular events in subjects with and without metabolic syndrome and hypertension. In this review, we focus on the results from the primary prevention statin trial, Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), which showed reductions in LDL, CRP, and cardiovascular events. Post-JUPITER, the new guidelines will now need to consider recommending high-sensitivity CRP testing to intermediate-risk metabolic syndrome patients and those with hypertension and intermediate risk so that we can better identify candidates at greater risk and reduce cardiovascular burden in these subjects with statin therapy.     

Metabolic syndrome, diabetes and cardiovascular events: current controversies and recommendations

Metabolic syndrome is now present in up to 40% of the United States adult population and is associated with a nearly a two fold increase in cardiovascular events, independent of the presence of diabetes mellitus. The concept of the metabolic syndrome as clinical syndrome has recently been challenged, however, and controversy exists as to whether the metabolic syndrome adds to cardiovascular risk above and beyond the sum of its independent metabolic components. Given the epidemic of obesity in both industrialized and third world countries, this issue is of great importance. The current article puts this controversy into perspective and explores the association of metabolic syndrome with both accelerated cardiovascular risk and the risk of development of type 2 diabetes. The pathophysiology of the increased risk of cardiovascular disease in diabetes associated with metabolic syndrome is discussed and the importance of early recognition of metabolic syndrome and potential role of addressing insulin resistance is stressed. Clearly more data is needed, but it is safe to say that metabolic syndrome is a worldwide epidemic in association with central obesity and underlying insulin resistance, which will propel a marked increase in cardiovascular events and diabetes mellitus in the years to come. Further research is needed to understand the role of more aggressive therapy in preventing type 2 diabetes and cardiovascular events in the population.     

The predictive role of C-reactive protein in patients with hypertension and subclinical atherosclerosis

Background: Recent guidelines published by the joint European Society of Hypertension/European Society of Cardiology have suggested the inclusion of C-reactive protein (CRP) in the standard assessment of cardiovascular risk in hypertensive patients, but few data are available on the role of CRP in patients with carotid lesions.
Methods: We studied 472 patients, 236 with and 236 without hypertension, sex- and age-matched, with and without early stages of atherosclerosis (e.g. those with an asymptomatic intima–media thickness of >0.9 mm), the influence of all the other traditional cardiovascular risk factors (e.g. older age, male sex, obesity, diabetes, smoking habit, family history of coronary artery disease, dyslipidaemia) and of high-sensitivity CRP levels on cerebrovascular and cardiovascular events in a 5-year follow up.
Results: At the end of follow up, patients with hypertension had more events than those without (25% vs 17%, P < 0.05). Proportional hazard analysis revealed in the group of patients without hypertension the presence of baseline carotid lesions ( P = 0.02) as predictor of events. In patients with hypertension, the presence of baseline carotid lesions ( P = 0.04) and elevated CRP levels ( P = 0.02) predicted clinical events. Patients with hypertension also showed a significant relationship between clinical events and quintiles of CRP levels ( P < 0.01).
Conclusion: Beyond the utility of high-sensitivity CRP levels in the prediction of early and late stages of atherosclerosis and subsequently on its association with clinical events, the therapeutic implications of these results remain to be evaluated by further studies.     

The predictive value of C-reactive protein in end-stage renal disease: is it clinically significant?

Cardiovascular disease is the leading cause of death in patients with end-stage renal disease. Besides traditional risk factors, disturbances in mineral and bone metabolism and inflammation are thought to be responsible for the increased risk of death. In the last years C-reactive protein (CRP) has gained a lot of attention in the general population, especially with regard to its link with atherosclerosis. Although several studies suggest that CRP may be useful as a parameter in predicting future cardiovascular events in both the general population and in patients with end-stage renal disease, there is doubt about the clinical evidence of this assumption. A statistical association between CRP and cardiovascular disease was observed in various studies, but the predictive power of this association is markedly diminished when adjusted for other risk factors. The relative contributions of CRP as a marker, as a causative agent, or as a consequence of atherosclerotic vascular disease are unclear, both in the general population and in the dialysis population. The CRP levels are highly variable and influenced by intercurrent events in dialysis patients. In dialysis patients, it is possible to reduce the CRP levels by statins, although these agents do not reduce the cardiovascular mortality in diabetic dialysis patients.     

The effects of metabolic syndrome versus infectious burden on inflammation, severity of coronary atherosclerosis, and major adverse cardiovascular events

BACKGROUND: The clinical predictors of inflammation in atherosclerosis remain controversial. The objective of this study was to compare the associations of metabolic factors vs. infectious burden (IB) with inflammation, the severity of coronary atherosclerosis, and major adverse cardiovascular events (MACEs). DESIGN, SETTING, AND PATIENTS: Coronary angiography with Gensini score was applied to assess the severity of coronary atherosclerosis in 568 patients with coronary artery disease. Metabolic syndrome (MS) score (0-5) was defined according to the modified criteria of National Cholesterol Education Program Adult Treatment Panel III. IB score (0-7) was defined as the number of seropositivities to several agents. RESULTS: IB score was not associated with plasma C-reactive protein (CRP) concentration, Gensini score, or the risk of MACE. In contrast, MS score significantly correlated with both plasma CRP concentration and Gensini score (P < 0.001 for both). MS score and plasma CRP concentration were also significantly associated with the risk of MACE (hazard ratios 1.51, P < 0.001; and 1.90, P = 0.002, respectively). CONCLUSION: Compared with IB, metabolic abnormalities have a more prominent association with the degree of inflammation, the severity of coronary atherosclerosis, and the risk of MACE in patients with coronary artery disease.     

Statins and C-reactive protein levels

In patients with or at risk for cardiovascular disease (CVD), including hypertensive individuals, lowering levels of low-density lipoprotein cholesterol (LDL-C) reduces CVD risk. Statins are the most effective of available therapies for lowering LDL-C. Extensive clinical trial data have shown that the degree of LDL-C reduction obtained depends on the particular statin used and that intensive LDL-C lowering reduces the incidence of cardiovascular events compared with more moderate LDL-C lowering. More recent data suggest that effects independent of LDL-C lowering may also play a part in the reduction in cardiovascular events. C-reactive protein (CRP), a marker of inflammation, is a potential predictor of CVD risk, and statins reduce CRP levels by up to 60%. CRP reduction is independent of LDL-C lowering, and variation between statins in CRP reduction may play some role in CVD event reduction rates. At present, however, there are few outcome data relating to the cardiovascular benefits of reducing CRP.