Relations of plasma high-sensitivity C-reactive protein to traditional cardiovascular risk factors

Variations of circulating C-reactive protein (CRP) levels are supposed to reflect chronic inflammatory process of the cardiovascular system. In particular, it has been reported that high-sensitivity CRP (hsCRP) is a promising marker of coronary heart disease. In the present study, we assessed the relationship between hsCRP and classic cardiovascular risk factors, such as age, blood pressure, smoking habit and serum lipids. Plasma hsCRP was measured by ELISA in 908 subjects, aged 30-79 years, who entered our health-check program. Plasma hsCRP level was 0.54+/-0.02 mg/l in 566 subjects without any disease currently treated. The level was significantly higher in patients treated for hypertension (0.74+/-0.06 mg/l, P=0.002), diabetes mellitus (0.77+/-0.09 mg/l, P=0.016) or coronary artery disease (0.99+/-0.16 mg/l, P=0.008) than in subjects without diseases. In a simple regression analyses of the 566 subjects without diseases, plasma hsCRP positively correlated with male gender, smoking, body mass index, systolic blood pressure, white blood cell count, blood hemoglobin, fasting blood glucose, serum gamma-GTP, uric acid and triglycerides, and inversely correlated with serum albumin and HDL-cholesterol. In multiple regression analysis, white blood cell count (r=0.276, P<0.001), body mass index (r=0.246, P<0.001), age (r=0.122, P=0.001) and smoking (r=0.112, P=0.009) showed independent correlations with plasma hsCRP. It is suggested that variation of circulating hsCRP, even within normal range, is involved in the interrelation of cardiovascular risk factors, such as age, smoking, obesity, high blood pressure and dyslipidemia, which are supposed to promote atherosclerosis and ultimately provoke cardiovascular diseases, such as coronary artery disease.     

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.     

High-sensitivity C-reactive protein as cardiovascular risk marker in patients with diabetes mellitus

C-reactive protein (CRP) is a liver-derived pattern recognition molecule that is increased in inflammatory states. It rapidly increases within hours after tissue injury, and it is suggested that it is part of the innate immune system and contributes to host defense. Since cardiovascular disease is at least in part an inflammatory process, CRP has been investigated in the context of arteriosclerosis and subsequent vascular disorders. Based on multiple epidemiological and intervention studies, minor CRP elevation [high-sensitivity CRP (hsCRP)] has been shown to be associated with future major cardiovascular risk (hsCRP:<1 mg/L=low risk; 1-3 mg/L=intermediate risk; 3-10 mg/L=high risk; >10 mg/L=unspecific elevation). It is recommended by the American Heart Association that patients at intermediate or high risk of coronary heart disease may benefit from measurement of hsCRP with regard to their individual risk prediction. Elevation of hsCRP is associated with increased risk of type 2 diabetes development in patients with all levels of metabolic syndrome. In type 1 and type 2 diabetes mellitus, hemoglobin A1c significantly correlates with hsCRP levels and future cardiovascular risk. Also, hsCRP levels increase with the stage of beta-cell dysfunction and insulin resistance. Non-diabetes drugs that have been shown to reduce hsCRP concentrations include aspirin, statins, cyclooxygenase-2 inhibitors, and fibrates. Recent intervention studies have also demonstrated the distinct efficacy of different anti-diabetes treatments on a variety of cardiovascular risk markers. Intensive insulin therapy may reduce inflammation, but this effect may be influenced by the degree of weight gain. Treatment with peroxisome proliferator-activated receptor gamma has lead to substantial reduction of hsCRP and other cardiovascular risk markers in several comparator studies. Since this effect was shown to be independent of the degree of glycemic improvement, it can be regarded as a classspecific effect. Whether these findings translate into a reduction of overall cardiovascular mortality will soon be shown by the currently running thiazolidinedione outcome studies. Positive results in these trials will further strengthen the value and acceptance of hsCRP, which is recommended as a predictive laboratory marker for cardiovascular disease risk also in patients with diabetes mellitus.     

High-sensitivity C-reactive protein and cardiovascular risk in patients with coronary heart disease

High-sensitivity C-reactive protein levels have received widespread attention because of a multitude of prospective studies that have shown that high levels of high-sensitivity C-reactive protein identify increased risk of initial cardiovascular events in coronary heart disease patients and increased risk of recurrent cardiac events in patients with stable and unstable angina, patients with acute myocardial infarction, and patients undergoing elective coronary revascularization procedures. In contrast to several other inflammatory markers, high-sensitivity C-reactive protein measurements are standardized and reproducible. The clinical significance of a reliable inflammatory marker includes identification of high-risk individuals, a gauge to monitor the activity of the disease, and a potential therapeutic target to alter the inflammatory component of the disease process. This review focuses on the importance of high-sensitivity C-reactive protein in cardiovascular risk stratification in coronary heart disease patients and discusses several preventive therapies that may reduce cardiovascular risk through reduction in high-sensitivity C-reactive protein.     

C-reactive protein distribution and correlation with traditional cardiovascular risk factors in the Italian population

BackgroundC-reactive protein (CRP) increases during an inflammatory response; its plasma levels are believed to be an independent predictor of future atherosclerotic disease. We report the distribution of plasma levels of CRP and its possible relationship with other cardiovascular risk factors in an Italian cohort.MethodsCRP was assessed in frozen plasma samples of 1949 participants in the CHECK study (2001–2005), which collected clinical and biochemical data from randomly selected subjects (40–79 years) in the setting of Italian general practice.ResultsMedian CRP (interquartile range) was higher in women (1.42 [0.58–2.86] vs 1.28 [0.58–2.50]; p = .163), in people aged ≥ 65 years (1.74 [0.89–3.34] vs 1.11 [0.52–2.45]; p < .001), in patients with obesity (2.37 [1.27–4.15] vs 1.16 [0.52–2.41]; p < .001), metabolic syndrome (2.12 [1.16–3.72] vs 1.10 [0.50–2.38]; p < .001), or higher cardiovascular risk (2.03 [1.01–3.42] vs 1.19 [0.53–2.50]; p < .001). Stepwise regression analysis showed significant associations (R² = .264) of circulating log_eCRP with body mass index, fibrinogen, apoB, age, gender, smoking habits, physical inactivity, creatinine levels, and systolic blood pressure.ConclusionThis study provides epidemiological data of CRP in the Italian population and reinforces the existing evidences about the close correlation between CRP and markers of inflammation and adiposity.     

High-sensitivity C-reactive protein and ankle brachial index in a finnish cardiovascular risk population

High-sensitivity C-reactive protein (hsCRP) has been previously linked to different forms of vascular disease. However, some studies have not found any relationship between hsCRP and atherosclerosis. Also, studies investigating correlation between hsCRP and ankle brachial index (ABI) are scarce. We studied hsCRP in a cardiovascular risk population with a special interest in correlation between hsCRP and ABI. All men and women aged 45 to 70 years from a rural town Harjavalta, Finland were invited to participate in a population survey. Diabetics and people with known vascular disease were excluded. Seventy-three percent (n = 2085) of the invited persons participated and 70% of the respondents (n = 1496) had at least one risk factor to cardiovascular diseases. These subjects were invited to further examinations. From them we measured ABI, hsCRP, leukocyte count, glucose tolerance, systemic coronary risk evaluation (SCORE), body mass index (BMI), and waist circumference. Mean hsCRP was 1.9 mg/L. Smokers had higher hsCRP (mean 2.2 mg/L) than nonsmokers (mean 1.8 mL/L). hsCRP in women was higher than in men (mean 2.0 mg/L versus 1.8 mg/L). Mean ABI was 1.10, and the prevalence of peripheral arterial disease was 3.1%. ABI correlated weakly with hsCRP (r = −0.077, p = 0.014), leukocyte count (r = −0.107, p = 0.001), and SCORE (r = −0.116, p = 0.001). It did not have correlation between age, weight, BMI, or waist circumference. hsCRP correlated with BMI (r = 0.208, p < 0.0001) and waist circumference (r = 0.325, p < 0.0001). When we excluded subjects with hsCRP >10 mg/L, ABI no longer correlated with hsCRP. In a cardiovascular risk population, hsCRP has only a weak correlation with ABI, and this correlation disappeared when we excluded subject with hsCRP >10 mg/L. Instead, hsCRP was correlated to the measures of obesity (waist circumference and BMI), indicating its role as a marker of adipose tissue–driven inflammation. hsCRP does not seem to be a suitable screening method for peripheral arterial disease.     

High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease

Inflammation plays a major role in atherothrombosis, and measurement of inflammatory markers such as high-sensitivity C-reactive protein (HSCRP) may provide a novel method for detecting individuals at high risk of plaque rupture. Several large-scale prospective studies demonstrate that HSCRP is a strong independent predictor of future myocardial infarction and stroke among apparently healthy men and women and that the addition of HSCRP to standard lipid screening may improve global risk prediction among those with high as well as low cholesterol levels. Because agents such as aspirin and statins seem to attenuate inflammatory risk, HSCRP may also have utility in targeting proven therapies for primary prevention. Inexpensive commercial assays for HSCRP are now available; they have shown variability and classification accuracy similar to that of cholesterol screening. Risk prediction algorithms using a simple quintile approach to HSCRP evaluation have been developed for outpatient use. Thus, although limitations inherent to inflammatory screening remain, available data suggest that HSCRP has the potential to play an important role as an adjunct for global risk assessment in the primary prevention of cardiovascular disease.     

High-sensitivity C-reactive protein is quite low in Japanese men at high coronary risk.

BACKGROUND: Although numerous studies have demonstrated a positive association of high-sensitivity C-reactive protein (CRP) with the incidence of coronary heart disease (CHD), little information exists regarding this issue in Japanese. METHODS AND RESULTS: The association between CRP and the Framingham Risk Score (FRS) was investigated in 2,523 middle-aged Japanese men without a medical history of CHD. CRP was significantly associated with this score obtained from all FRS factors. After dividing subjects into 4 categories of relative risk estimate for CHD, the geometric mean of CRP (mg/L) increased gradually with the CHD risk (below average: 0.39 [95% confidence interval, 0.37-0.41], average: 0.58 [0.50-0.67], moderately above average: 0.70 [0.57-0.86], high: 0.79 [0.58-1.09], trend p<0.001). However, it should be noted that the mean CRP concentration of the high-risk group was only 0.79 mg/L and a greater proportion (63.8%) of the high-risk subjects was in the low-risk range of CRP (<1 mg/L). CONCLUSIONS: Circulating CRP well reflect the estimated CHD risk, indicating that CRP may be useful for coronary risk stratification in Japanese also. However, the details of the CRP level in Japanese must be investigated further by prospective studies to determine the Japanese-specific cutoff points for CHD risk evaluation.     

血清超敏C反应蛋白与心血管危险因素的关系

目的：探讨血清超敏C反应蛋白（hs—CRP）与心血管危险因素的关系。方法：对,388例健康成人（男223例,女165例,年龄47～53岁）的身高、体重、血压、心电图、血糖、血脂及血清hs～CRP等进行测定。结果：由低至高的血清hs—CRP四等分组（〈2．1mg／L,2．1～5．0mg／L,5．1～8．0mg／L,〉8．0mg／L）的心血管危险因素体重指数、血压、空腹血糖、高密度脂蛋白-胆固醇（HDL—C）组间差异非常显著（F=7．63～22．46,P均〈0．001）,总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白-胆固醇（LDL—c）的组间差异有显著性（F=2．89～8．88,P分别为0．031,0．022,0．015）,四组心血管危险因素聚集检出率分别为32．3％,48．9％,58．0％,79．4％．差异有显著性（x^2=28．12,P〈0．001）。结论：血清hs—CRP与心血管危险因素（体重指数、血压、血糖和血脂）有关。     

High-sensitivity C-reactive protein: a novel cardiovascular risk predictor in type 2 diabetics with normal lipid profile

Background

India is the diabetic capital of the world. Coronary heart disease is a major cause of morbidity and mortality among diabetics. Type 2 diabetes mellitus and atherosclerosis are complex diseases sharing common antecedents like inflammation. High-sensitivity C-reactive protein (hs-CRP), an acute phase reactant protein, is a proinflammatory atherogenic circulating marker which can prove to be an independent cardiac risk predictor.

Aim

The aim of the present study was to evaluate the role of hs-CRP as an independent cardiovascular risk marker among Indians with type 2 diabetes with normal lipid profile.

Settings and Design

This was a case control study including 60 type 2 diabetics with normal lipid profile and 60 age- and sex-matched healthy controls.

Materials and Methods

Twelve-hour fasting blood samples were collected from all the participants. Serum was assayed for hs-CRP and lipid profile.

Statistical Analysis

Results were analyzed by unpaired t test.

Results

We found elevated hs-CRP levels (4.8±0.2, P<.0001) among cases compared to controls (0.9±0.1). According to hs-CRP levels, seven cases were in the low-risk (<1 mg/l), 32 in the moderate-risk (1–3 mg/l), and 21 in the high-risk (3–10 mg/l) group with mean values of hs-CRP of 0.7±0.2, 1.75±0.7, and 5.8±1.4, respectively. Relative risk was 4.75 with odds ratio of 10.23 (95% confidence interval 8.8–11.23).

Conclusion

The study suggests that hs-CRP is an independent cardiac risk predictor even with normal lipid profile and can help measure additional risk. The American Heart Association stated that patients in the intermediate- and high-risk group may benefit from therapeutic lifestyle change and that cardiovascular event may be prevented.     

High-sensitivity C-reactive protein level is a significant risk factor for silent cerebral infarction in patients on hemodialysis

In patients with chronic renal failure on hemodialysis (HD), silent cerebral infarctions (SCIs) are associated with high mortality. The levels of high-sensitivity C-reactive protein (HSCRP), a marker of inflammation and atherosclerosis, elevate with increasing renal dysfunction. We tested the hypothesis that increased HSCRP levels correlate with the occurrence of SCI in HD patients. By brain magnetic resonance imaging findings, we divided 54 patients undergoing HD into a with-SCI group (61 +/- 8 years, n = 30) and a without-SCI group (60 +/- 7 years, n = 24). We compared sex, body mass index, metabolic profiles, HSCRP levels, and smoking habits in Japanese patients on HD with and without SCI. We made the following observations: (1) The number of patients with diabetes or hypertension did not differ between the 2 groups. (2) The levels of HSCRP were higher in the with-SCI group in comparison with the without-SCI group (P < .0001). (3) The proportion of smokers was higher in the with-SCI group than in the without-SCI group (P < .05). (4) Plasma levels of high-density lipoprotein cholesterol were lower, whereas uric acid was higher, in the with-SCI group than in the without-SCI group (P < .05 and P < .0001, respectively). (5) Multivariate logistic analysis identified HSCRP levels as being significantly associated with the presence of SCI (odds ratio, 1.61; 95% confidence interval, 1.17-2.85; P < .001). This study indicates that patients in chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI and that HSCRP is significantly associated with the presence of SCI in HD patients.     

Elevated C-reactive protein is related to cognitive decline in older adults with cardiovascular disease

OBJECTIVES: To prospectively relate C‐reactive protein (CRP), a systemic marker of inflammation, to cognitive change over a 1‐year follow‐up period. DESIGN: Prospective 1‐year follow‐up. SETTING: Outpatient university medical setting. PARTICIPANTS: Seventy‐eight adults (aged 56–84; 39% female) with cardiovascular disease. MEASUREMENTS: CRP levels were measured using a high‐sensitivity assay, and participants completed a neuropsychological battery at study entry. Neuropsychological assessment was repeated 1 year later. RESULTS: The association between CRP and change in cognition over the 1‐year follow‐up was examined using hierarchical linear regression modeling for five cognitive domains (global cognition, language, memory, visuospatial abilities, and attention‐executive‐psychomotor). High CRP levels were associated with subtle declines in attention‐executive‐psychomotor performance (CRP β=?0.22, P=.04) after adjusting for the effects of age and cognitive performance at study entry. CRP was not significantly associated with change in language, memory, or visuospatial performance. CONCLUSION: These data provide preliminary evidence that inflammation, potentially contributing to atherosclerotic processes, may underlie the association between high CRP and changes in attention‐executive‐psychomotor performance.     

C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors

Whether or not C-reactive protein (CRP) predicts heart disease in adults because it is a marker of damage or atherosclerosis is difficult to assess. In children, there is no confounding with coronary disease or active smoking. We measured CRP in 699 children aged 10-11 years. CRP levels were 47% higher in girls than boys, and rose with age by 15%/year. CRP levels were 270% (95% CI, 155-439%) higher in the top fifth than the bottom fifth of Ponderal index (weight/height(3)). After adjustment, CRP levels remained 104% (95% CI, 23-236%) higher in the 56 children of South Asian origin. CRP was unrelated to: birth weight, height, social class, Helicobacter pylori infection or passive smoke exposure. CRP was correlated with several cardiovascular risk factors, but only fibrinogen (r = 0.33, P = 0.0001), HDL-cholesterol (r = -0.13, P = 0.0006), heart rate (r = 0.12, P = 0.002) and systolic blood pressure (r = 0.08, P = 0.02) remained statistically significant after adjustment. We conclude that adiposity is the major determinant of CRP levels in children while physical fitness has a small independent effect. The strong relationships with fibrinogen and HDL-cholesterol suggest a role for inflammation throughout life in the development of atherosclerosis and cardiovascular disease. Longitudinal studies are needed to determine whether these associations reflect long term elevations of these risk factors in some individuals, or short term fluctuations in different individuals.