C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men.

BACKGROUND: There is much interest in reported associations between serum C-reactive protein and incident ischaemic heart disease. It is uncertain what this association represents. We aimed to assess the effect of confounding from a number of different sources in the Caerphilly Prospective Heart Disease Study and in particular whether the low grade inflammation indicated by C-reactive protein may be the mechanism whereby non-circulating risk factors may influence pathogenesis of ischaemic heart disease. Methods: Plasma specimens collected during 1979-83 from 1395 men with sufficient sample remaining were assayed for serum C-reactive protein by ELISA. Subsequent mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records and electrocardiographic changes at 5-yearly follow-up examinations. RESULTS: There was a positive association between C-reactive protein and incident ischaemic heart disease (P<0.005) mainly with fatal disease (P<0.002). There was also a positive association with all-cause mortality (P<0.0001). C-reactive protein was significantly associated with a number of non-circulating risk factors including body mass index (P<0.0001), smoking (P<0.0001), low forced expiratory volume in 1 s (P<0.0001), height (P=0.025), low childhood social class (P=0.014) and age (P=0.036). C-reactive protein was also associated positively with circulating risk factors including viscosity, leukocyte count, fibrinogen (all P<0.0001) and insulin (P=0.0058). After adjustment for non-circulating risk factors the association with all-incident ischaemic heart disease and ischaemic heart disease death became non-significant, but the association with all-cause mortality remained (P=0.033). Further adjustment for fibrinogen however removed any hint of an increasing trend in odds for all three outcomes. CONCLUSION: C-reactive protein levels are raised in association with a variety of established cardiovascular risk factors. Neither C-reactive protein nor the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease.     

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.     

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.     

Survey of C-reactive protein and cardiovascular risk factors in apparently healthy men

Several prospective studies have demonstrated a direct association between C-reactive protein (CRP) levels and the risks of developing cardiovascular disease. Few studies, however, have explored the interrelations between CRP levels and other risk factors for cardiovascular disease. We evaluated the relation of CRP with several cardiovascular risk factors in a cross-sectional survey of 1,172 apparently healthy men. There were significant positive associations between CRP levels and age, number of cigarettes smoked per day, body mass index, systolic and diastolic blood pressure, total cholesterol, triglycerides, lipoprotein(a), apolipoprotein B, tissue-type plasminogen activator antigen, D-dimers, total homocysteine, and fibrinogen (all p values <0.05). Significant inverse associations were observed for exercise frequency, high-density lipoprotein cholesterol, and apolipoprotein A-I and A-II (all p values <0.02). In multivariate analysis, age, smoking status, and serum levels of tissue-type plasminogen activator antigen, fibrinogen, lipoprotein(a), and total homocysteine were independent correlates of CRP levels. Finally, in an analysis controlled either for all the independent correlates or for several usual risk factors, we observed progressive increases in levels of CRP with increasing prevalence of risk factors (p for trend <0.001 for independent correlates and <0.01 for usual risk factors). In conclusion, in a large cohort of apparently healthy men, CRP levels were associated with several cardiovascular risk factors. These data are compatible with the hypothesis that CRP levels may be a marker for preclinical cardiovascular disease.     

C-reactive protein, adiposity and cardiovascular risk factors in a Mediterranean population

BACKGROUND: Understanding the distribution of high-sensitivity C-reactive protein (CRP) and its relations with classic cardiovascular risk factors in specific populations is important for further diagnostic use. METHODS: We studied 1,157 adult subjects (652 women and 505 men) participating in the Health Study of Catalonia. CRP concentrations were measured with a high-sensitivity turbidimetric assay. RESULTS: Median levels of CRP were 1.57 mg/l and 25% of both men and women had CRP values >3 mg/l. No differences were observed between men and women even after adjustment for age and body mass index (BMI). After patients with CRP values above the 97.5th percentile (n = 31) had been excluded, CRP concentrations increased significantly with increasing levels of cardiovascular risk factors in both men and women. Men and women with metabolic syndrome showed significantly higher levels of CRP than their counterparts, even after adjustment for BMI and age. In a multiple regression analysis, BMI, triglycerides and fasting glucose were independent predictors of CRP in women and together explained 42% of its variance. In men, CRP was independently and positively associated to waist circumference, smoking, diastolic blood pressure, uric acid and triglycerides, and negatively associated to HDL-cholesterol. Altogether these variables explained 51% of its variability. CONCLUSIONS: The present study describes, for the first time, CRP concentrations in a sample that is representative of a Spanish Mediterranean community. CRP distribution and correlates are very similar to those reported previously in spite of the different lifestyle and nutritional habits, and the lower rates of cardiovascular diseases in our population.     

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。     

Carotid and femoral atherosclerosis, cardiovascular risk factors and C-reactive protein in relation to smokeless tobacco use or smoking in 58-year-old men

Objectives. To examine the associations between smokeless tobacco use, smoking, cardiovascular risk factors, inflammation and ultrasound-assessed measures of atherosclerosis in the carotid and femoral arteries. Subjects. The study was performed in a population-based sample of clinically healthy men (n = 391) all 58 years old. Exclusion criteria were cardiovascular or other clinically overt diseases or continuous medication with cardiovascular drugs. Methods. The habits of smoking and oral moist snuff use were assessed by questionnaires. C-reactive protein (CRP) was assessed by high sensitive enzyme-linked immunosorbent assay (ELISA). Intima-media thickness (IMT) in the carotid bulb, the common carotid artery and the common femoral artery and plaque occurrence were measured by ultrasound. Results. The use of oral moist snuff was associated with serum triglycerides and waist-hip ratio (WHR), but not with CRP or ultrasound-assessed measures of subclinical atherosclerosis. Smoking, on the other hand, was associated with CRP, the components in the metabolic syndrome and IMT as well as plaques in the carotid and femoral arteries. In comparison to never-smokers the current smokers had higher values of WHR, triglycerides, C-reactive protein and IMT in carotid bulb and femoral artery. Ex-smokers were in general more obese and had a femoral IMT that was in-between that of never-smokers and current smokers. Conclusions. Tobacco smoking, but not oral moist snuff use, was associated with carotid and femoral artery IMT, and increased levels of CRP. Current smoking was also associated with abdominal obesity. Ex-smokers though, are generally more obese. Smoking was also associated with hyperinsulinaemia, dyslipidaemia and high blood pressure, i.e. the metabolic syndrome. The inhaled smoke from the combustion of tobacco seems to be an important aetiological factor in the atherosclerotic process.     

The relationship between C-reactive protein and other cardiovascular risk factors in men and women

INTRODUCTION: C-reactive protein (CRP) has emerged as an important indicator of risk for cardiovascular disease. The impact of gender on the relationship between CRP and other cardiovascular risk factors, however, has not been thoroughly investigated. METHODS: Ninety men and 75 women participated in this study. Age, resting systolic and diastolic blood pressure, resting heart rate, body mass index, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and hs-CRP were ascertained. Maximal oxygen consumption was obtained via treadmill testing, and aortic stiffness was measured using magnetic resonance imaging. RESULTS: Log hs-CRP level was significantly higher in the female subjects compared with the males subjects (0.86 +/- 0.67 mg/L vs 0.63 +/- 0.44 mg/L, respectively; P = .003). In the male group, Pearson product moment correlation analysis showed that log hs-CRP was not significantly correlated (P > .10) with any of the other variables of interest. In the female group, however, log hs-CRP was significantly correlated (P < .05) with total cholesterol (r = 0.30), low-density lipoprotein (r = 0.27), tryglycerides (r = 0.51), and body mass index (r = 0.36). Linear regression analysis determined that triglycerides and body mass index explained 30% of the variability in log hs-CRP. CONCLUSIONS: These results indicate that the relationship between CRP and other cardiac risk factors is different between apparently healthy men and women. The prognostic characteristics of CRP and the impact of statin therapy on CRP may therefore differ between men and women. Future research should be directed toward resolving this issue.     

High-sensitivity C-reactive protein is only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors

BACKGROUND: The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors. METHODS: In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction]. RESULTS: Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001). CONCLUSION: After adjustment for traditional CV risk factors hsCRP was only associated with PWV and atherosclerotic plaques, indicating a possible effect of low-grade inflammation on macrovascular damage. The close relationship between traditional CV risk factors and hsCRP suggested that hsCRP was an integrated CV risk marker early in the development of atherosclerosis.     

Thromboxane biosynthesis and metabolism in relation to cardiovascular risk factors

Enhanced platelet biosynthesis of thromboxane A(2) is associated with several cardiovascular risk factors, as a consequence of a direct effect on platelet biochemistry and/or some form of endothelial dysfunction. Moreover, episodic increases in thromboxane biosynthesis occur in acute coronary and cerebral ischemic syndromes. Thromboxane-dependent platelet activation represents an important mechanism that amplifies the consequences of acute vascular lesions as well as those of longstanding metabolic or hemodynamic disturbances, and results in increased risk of vascular occlusive events.     

Dietary patterns,cardiovascular risk factors and C-reactive protein in a healthy Italian population

Background and aimsDietary habits have been associated with cardiovascular disease (CVD) risk factors. This study aimed at evaluating the association of non-predefined dietary patterns with CVD risk profile and C-reactive protein (CRP).Methods and resultsWe analyzed 7646 healthy subjects from the Moli-sani project, an on-going cross-sectional cohort study of men and women aged ≥35, randomly recruited from a general Italian population. The Italian EPIC food frequency questionnaire was used. Food patterns were generated using principal factor analysis (PFA) and reduced rank regression (RRR).Three dietary patterns were identified by PFA. The “Olive Oil and Vegetables” pattern, characterized by high intake of olive oil, vegetables, legumes, soups, fruits and fish, was associated with relatively lower values of glucose, lipids, CRP, blood pressure and individual global CVD risk score. The “Pasta and Meat” pattern, characterized by high intake of pasta, tomato sauce, red meat, animal fats and alcohol, was positively associated with glucose, lipids, CRP and CVD risk score. The “Eggs and Sweets” pattern, characterized by positive loadings of eggs, processed meat, margarines, butter, sugar and sweets, was associated with high values of CRP. The first RRR pattern was similar to the “Pasta and Meat” pattern both in composition and association with CVD risk profile.ConclusionsIn a large healthy Italian population, non-predefined dietary patterns including foods considered to be rather unhealthy, were associated with higher levels of cardiovascular risk factors, CRP and individual global CVD risk, whereas a “prudent–healthy” pattern was associated with lower levels.     

C-reactive protein, cardiovascular risk factors and the association with myocardial infarction in men

OBJECTIVES: This study had three objectives: first, to investigate the association of C-reactive protein levels and myocardial infarction amongst men; secondly, to study the associations of C-reactive protein levels with cardiovascular risk factors; and thirdly, to adjust the risk of myocardial infarction for such factors. DESIGN AND SUBJECTS: A case-control study including 560 patients with a first myocardial infarction who had survived at least 6 months, plus 646 control subjects. RESULTS: Patients had significantly higher levels of C-reactive protein (mean 2.2 mg L-1) than control subjects (mean 1.7 mg L-1; P < 0.001). Persons in the highest quintile of C-reactive protein had an unadjusted 1.9-fold increased risk of myocardial infarction compared with persons in the lowest quintile (odds ratio 1.9, 95% CI: 1.3-2.7). C-reactive protein was, in addition to smoking, associated with several cardiovascular risk factors: age, obesity, diabetes, blood pressure, triglycerides and inversely associated to HDL cholesterol. Adjustment for these variables, especially for total cholesterol, HDL cholesterol and triglycerides, substantially decreased the risk of myocardial infarction for persons in the highest quintile of C-reactive protein, compared to those in the lowest quintile, to 1.3 (95% CI: 0.9-1.9). CONCLUSIONS: Our findings confirm previous reports that C-reactive protein predicts the risk of myocardial infarction. However, this association does not appear to be causal, since the increase in risk can to a large extent be explained by the presence of other cardiovascular risk factors.     

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.     

Relationships among changes in C-reactive protein and cardiovascular disease risk factors with lifestyle interventions

Background and aimsInflammation plays a role in the development of cardiovascular disease (CVD). Elevated levels of the inflammatory marker, C-reactive protein (CRP), are cross-sectionally associated with traditional CVD risk factors and are being considered as an emerging CVD risk factor. In a secondary data analysis, we examined changes in CRP and several CVD risk factors after one-year diet and physical activity interventions to assess whether CRP changed concurrently with other risk factors, or was independent of the traditional risk factors.Methods and resultsData were analyzed from 143 men and 133 women with dyslipidemia who were randomized to one-year interventions of low-fat diet only, physical activity only, diet plus physical activity, or control. Plasma high-sensitivity CRP, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (TG), fasting and 2-hr blood glucose and insulin, blood pressure (BP), and waist circumference were obtained at baseline and follow-up. Multiple linear regression models were used to predict CRP change based on other risk factor changes, controlling for age, race, alcohol intake, and hormone replacement therapy. Treatment groups were combined for analysis. Baseline mean (SD) CRP levels were 1.3 ± 1.3 (men) and 1.9 ± 1.8 mg/L (women), with mean changes of ?0.11 ± 1.3 and ?0.17 ± 1.5 mg/L, respectively. Plasma CRP change was negatively associated with TG change in men (p = 0.003) and women (p = 0.05), positively associated with change in systolic BP in men (p = 0.01), but was not associated with changes in the other risk factors.ConclusionDietary and/or physical activity induced changes in CRP may be largely independent of traditional CVD risk factors in persons with dyslipidemia.     

Serum cholesterol, other risk factors, and cardiovascular disease in a Japanese cohort

The relationship of serum cholesterol and other risk factors to cardiovascular disease was investigated in a 16-year cohort of 16,711 residents of Hiroshima and Nagasaki. Examined in detail were the relationship of serum cholesterol, and the joint relationships of serum cholesterol, systolic blood pressure, diastolic blood pressure, and other risk factors to coronary heart disease (CHD), cerebral infarction (CI), and cerebral hemorrhage (CH). Baseline and biennially collected risk factor data were analyzed. The latter type of measurement permitted separate investigation of both the short-term and long-term effects of cholesterol measurements. In both types of analyses, both serum cholesterol and blood pressure showed strong associations with CHD incidence. In particular, there were strong associations with short-term and delayed CHD incidence. Furthermore, the association of cholesterol with short-term CHD incidence could not be explained by its association with delayed CHD incidence, or vice versa. Multivariate analyses that also included several other risk factors (smoking habits, clinical diagnosis of diabetes mellitus, left ventricular hypertrophy or strain on electrocardiogram, relative body weight, hematocrit, and proteinuria) for which data were available showed such risk factors to be of lesser, but generally non-negligible, importance in this population. In the case of CH and CI, serum cholesterol was found to be weakly or not at all related to incidence of either disease while blood pressure remained a strong correlate. For CI some suggestion of a statistical interaction between blood pressure and serum cholesterol was found. Discussed are implications for theories of disease pathogenesis for CHD, CI and CH.