Association between pulse pressure and C-reactive protein among apparently healthy US adults

Elevated pulse pressure has been associated with an increased risk of cardiovascular disease, which is increasingly being seen as an inflammatory disease. Thus, the mechanism underlying the link between elevated pulse pressure and cardiovascular disease risk may be inflammation. However, investigators have not examined the relationship between pulse pressure and C-reactive protein, an inflammation marker that has been closely linked to cardiovascular risk. We examined the cross-sectional relationship between pulse pressure and C-reactive protein among 9867 healthy persons 17 years of age or older who participated in the Third National Health and Nutrition Examination Survey. The association between pulse pressure and the odds of having an elevated C-reactive protein level (> or = 0.66 mg/dL) was assessed by logistic regression. In a model that adjusted for systolic blood pressure, demographic factors, cholesterol, measures of obesity, smoking, alcohol consumption, physical activity, and antihypertensive medication use, a 10 mm Hg increase in pulse pressure was associated with a 15% increase in the odds of having an elevated C-reactive protein level (odds ratio, 1.15; 95% confidence interval, 1.01 to 1.31; P=0.04). When the same model was re-run adjusting for diastolic blood pressure instead of systolic blood pressure, a 10 mm Hg rise in pulse pressure was associated with a significant 12% increase in the odds of having an elevated C-reactive protein level. Systolic and diastolic blood pressure were unrelated to C-reactive protein once pulse pressure had been accounted for. Our results suggest that increases in pulse pressure are associated with elevated C-reactive protein levels among apparently healthy US adults, independent of systolic and diastolic blood pressure.     

Physical activity, C-reactive protein levels and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study.

BACKGROUND: Physical activity is inversely associated with the risk of future coronary artery disease. Whether this relationship is in part mediated by lower levels of systemic inflammation, as indicated by C-reactive protein concentrations, is unknown. METHODS: We performed a nested case-control study among apparently healthy men and women enrolled in the European Prospective Investigation into Cancer and Nutrition-Norfolk prospective population study, to investigate the relationship among habitual (work-related and leisure time) physical activity, cardiovascular risk factors and the risk of future coronary artery disease. RESULTS: Among men, those with an active lifestyle had a significantly lower risk of future coronary artery disease than those with an inactive lifestyle [odds ratio (OR) 0.65; 95% confidence interval (CI) 0.47-0.90; P for linearity, 0.008], after adjustment for smoking, systolic blood pressure, diabetes, body mass index and low-density lipoprotein and high-density lipoprotein cholesterol. Additional adjustment for C-reactive protein levels attenuated this relationship only slightly (OR 0.68; 95%CI 0.49-0.93; P for linearity, 0.02). Similarly, active women had an adjusted odds ratio of 0.48 (0.28-0.82; P for linearity <0.001) for future coronary artery disease compared with inactive women. Additional adjustment for C-reactive protein levels attenuated this relationship slightly (OR 0.51; 0.30-0.87; P for linearity, 0.003). CONCLUSIONS: We observed that people with an active lifestyle had a substantially lower risk of future coronary artery disease than people with an inactive lifestyle, and that this relationship was partly mediated through lower levels of established cardiovascular risk factors and in addition, C-reactive protein. This observation suggests that reduced systemic inflammation may be one of the mechanisms through which physical activity leads to reduced cardiovascular risk.     

Association between leisure time physical activity and markers of chronic inflammation related to coronary heart disease

BACKGROUND: Some markers of chronic inflammation have been recognized as predictors of cardiovascular risk in apparently healthy subjects and in patients with coronary heart disease (CHD). High sensitivity C-reactive protein (CRP) appears to be the most useful marker in clinical settings. Several studies reported associations between inflammatory markers and other cardiovascular risk factors, such as age, obesity, cholesterol levels, the presence of diabetes mellitus, physical activity, social level and smoking habits. We focussed on the association between C-reactive protein, serum amyloid A (SAA), fibrinogen and leisure time physical activity (LTPA). METHODS: This report deals with the results observed in a sub-sample of the BELSTRESS study. 892 male subjects, free from clinical CHD and major ECG abnormalities, working in the same environment, aged 35-59 years, were selected. A questionnaire was used to estimate the level of leisure time physical activity. Associations between CRP, SAA, fibrinogen and leisure time physical activity were evaluated through univariate and multivariate methods. Subjects taking statins or other lipid lowering medication were excluded from the study. RESULTS: Regular leisure time physical activity is associated with reductions of several cardiovascular risk factors, such as body mass index (BMI), waist hip ratio and the lipid profile. Smokers and low educated subjects had a lower physical activity status. Age adjustment did not alter the means of inflammatory parameters according to the levels of leisure time physical activity. After correction for personal characteristics (BMI, current smoking status, educational level, presence of diabetes and alcohol consumption) no significant relation was found between leisure time physical activity and levels of inflammatory markers. The differences of CRP and fibrinogen according to the level of physical activity, found in bivariate analysis, seem to be explained by linked differences in BMI, or related to current smoking habits. Leisure time physical activity, as reported in this study, is not significantly related to C-reactive protein, serum amyloid A or fibrinogen levels, after correction for other cardiovascular risk factors. CONCLUSION: These data indicate that leisure time physical activity, as reported in our study, is not an independent predictor of C-reactive protein, serum amyloid A or fibrinogen levels. Possible interactions of physical activity and other cardiovascular risk factors might explain the (indirect) relation we found in the bivariate analysis.     

Nontraditional risk factors for coronary heart disease incidence among persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND: Major risk factors explain much of the excess risk for coronary heart disease produced by diabetes, but nontraditional factors may also relate to incident coronary heart disease. OBJECTIVE: To examine the association of traditional and nontraditional risk factors with incidence of coronary heart disease in adults with diabetes. DESIGN: Prospective cohort study. SETTING: The Atherosclerosis Risk in Communities (ARIC) Study. PARTICIPANTS: 1676 middle-aged persons who had diabetes but no history of prevalent coronary heart disease. MEASUREMENTS: Multiple risk factors were recorded at baseline. Follow-up was from 1987 through 1995. RESULTS: 186 participants developed incident coronary heart disease events during follow-up. As expected, the incidence of coronary heart disease in participants with diabetes was associated positively with traditional risk factors (hypertension, smoking, total cholesterol level, and low high-density lipoprotein [HDL] cholesterol level). After adjustment for sex, age, ethnicity, and ARIC field center, incident coronary heart disease was also significantly associated with waist-to-hip ratio; levels of HDL3 cholesterol, apolipoproteins A-I and B, albumin, fibrinogen, and von Willebrand factor factor VIII activity; and leukocyte count. However, after adjustment for traditional risk factors for coronary heart disease, only levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count remained independently associated with coronary heart disease (P < 0.03). The relative risks associated with the highest compared with lowest groupings of albumin, fibrinogen, factor VIII, and von Willebrand factor values and leukocyte count were 0.64 (95% CI, 0.44 to 0.92), 1.75 (CI, 1.12 to 2.73), 1.58 (CI, 1.02 to 2.42), 1.71 (CI, 1.11 to 2.63), and 1.90 (CI, 1.16 to 3.13), respectively. Adjustment for diabetes treatment status attenuated these associations somewhat. CONCLUSIONS: Levels of albumin, fibrinogen, and von Willebrand factor; factor VIII activity; and leukocyte count were predictors of coronary heart disease among persons with diabetes. These associations may reflect 1) the underlying inflammatory reaction or microvascular injury related to atherosclerosis and a tendency toward thrombosis or 2) common antecedents for both diabetes and coronary heart disease.     

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.     

The interactions between cigarette smoking and reduced lung function on systemic inflammation

BACKGROUND: Low-grade systemic inflammation is commonly observed in conditions associated with reduced FEV(1). Active cigarette smoking, which is a leading risk factor for decreased FEV(1), can also independently induce systemic inflammation. STUDY OBJECTIVES: To determine the independent contributions of active cigarette smoking and reduced FEV(1) (as well as their potential interactions) on systemic inflammation. DESIGN: Cross-sectional survey. SETTING: The US general population. PARTICIPANTS: A total of 7,685 adult participants, >/= 40 years of age, in the Third National Health and Nutrition Examination Survey, who had acceptable data on spirometry and laboratory measurements such as serum C-reactive protein (CRP). MEASUREMENTS: The participants were stratified into four equal groups (quartiles) based on the percent predicted FEV(1) values. Each group was further categorized as active smokers or nonsmokers according to serum cotinine level (ie, >/= 10 or < 10 ng/mL). Serum levels of CRP, plasma fibrinogen, blood leukocytes, and platelets were compared across the predicted FEV(1) quartile groups and across smoking status using multiple logistic regression models. RESULTS: We found that active smoking by itself increased the odds of having elevated CRP levels by 63% (adjusted odds ratio [OR], 1.63; 95% confidence interval, 1.28 to 2.09). The adjusted OR for reduced FEV(1) was 2.27 (95% confidence interval, 1.92 to 2.70). Having both risk factors increased the OR to 3.31 (95% confidence interval, 2.73 to 4.02). Similar findings were observed for blood leukocytes and plasma fibrinogen. CONCLUSION: These findings suggest an additive effect of active smoking and reduced FEV(1) on markers of systemic inflammation and suggest their potential interactions in the pathogenesis of systemic complications observed in patients with poor lung function.     

Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease

BACKGROUND AND AIM: Leptin, an adipocyte-derived protein, regulating food intake and metabolism has been implicated in the development of coronary heart disease. We have examined the relationship between leptin and vascular risk factors including insulin resistance, metabolic, inflammatory and haemostatic risk factors. METHODS AND RESULTS: The study was carried out in 3640 non-diabetic men aged 60-79 years drawn from general practices in 24 British towns and who were not on warfarin. Leptin was strongly positively correlated with waist circumference (r=0.58; p<0.0001). Leptin concentrations decreased significantly with increasing physical activity and were lowered in cigarette smokers and elevated in men with pre-existing coronary heart disease and stroke; alcohol intake showed no association with leptin concentration. After adjustment for waist circumference and these lifestyle factors, increased leptin was independently associated with significant increases in insulin resistance, triglycerides, inflammatory markers (interleukin-6, C-reactive protein, fibrinogen, plasma viscosity), coagulation factor VIII, endothelial markers von Willebrand factor, tissue plasminogen activator, and fibrin D-dimer levels; and a decrease in HDL-cholesterol. No association was seen between leptin and blood pressure, total cholesterol, glucose or white cell count after adjusting for waist circumference. Further adjustment for insulin resistance abolished the relationships between leptin and triglycerides and HDL-cholesterol, weakened the associations with the haemostatic factors although they remained significant, but made minor differences to the associations with inflammatory markers. CONCLUSION: Plasma leptin is associated with insulin resistance, inflammation and disturbances in haemostasis independent of waist circumference, suggesting possible pathways by which leptin may influence risk of cardiovascular disease.     

Serum C-reactive protein and self-reported stroke: findings from the Third National Health and Nutrition Examination Survey

C-reactive protein may predict the risk of coronary heart disease, but its association with stroke has not been well studied. We used data from the Third National Health and Nutrition Examination Survey, conducted from 1988 to 1994, to examine the association between serum C-reactive protein concentrations and self-reported past history of stroke among 8850 US men and women aged >/=40 years. The unadjusted geometric mean of C-reactive protein concentration was higher among participants with stroke than those without stroke (0. 45+/-0.02 versus 0.32+/-0.01, P<0.001). After adjusting for age, sex, race or ethnicity, education, smoking status, systolic blood pressure, serum cholesterol, high density lipoprotein cholesterol, history of diabetes mellitus, body mass index, and physical activity, the odds ratio for stroke among participants with C-reactive protein concentrations >/=0.55 mg/dL compared with participants with concentrations 相似文献   

Inflammation, coagulation, and depressive symptomatology in cardiovascular disease-free people; the ATTICA study.

BACKGROUND: Depression is associated with an increase in cardiovascular disease, but the underlying mechanisms are not well understood. The aim of this study was to examine the associations of depressive symptoms with inflammation and coagulation factors related to cardiovascular risk in persons free of cardiovascular disease. METHODS: A random algorithm was developed and stratified by gender-age and multistage sampling was performed during 2001-2002. In this study, we analysed data from 453 men (19-89 years old) and 400 women (18-84 years old). Inflammation markers were C-reactive protein (CRP), serum amyloid A, white blood cell (WBC) and total platelet counts; and coagulation factors including homocysteine and fibrinogen. Depression was assessed with the Zung Self-Rating Depression Scale (ZDRS range 0-100) after validation for the study population. A ZDRS score of 50 or more classified a person as mildly depressive. Statistical adjustments were made for risk factors (age, gender, smoking, diabetes mellitus, and physical activity level). RESULTS: Women had significantly higher scores on the Zung depression scale than men (47 +/- 9 vs. 43 +/- 10, p<0.001). Thus, 21% of men and 27% of women had mild depression, while 4% of men and 6% of women had severe depressive symptomatology. The depression scale correlated positively with C-reactive protein levels (p<0.05), white blood cell count (p<0.05), and fibrinogen (p<0.05) in both genders after adjustment for control variables. CONCLUSION: This study revealed that depression was associated with inflammation and coagulation factors in cardiovascular disease-free people, suggesting a possible pathway leading to an increased frequency of events of coronary heart disease in depressive individuals.     

Role of novel markers of inflammation in patients with stable coronary heart disease

The role of novel markers of inflammation in patients with coronary heart disease (CHD) is still unclear. We conducted a case-control study to assess the association between various markers of inflammation and the presence and severity of chronic stable CHD. We included 312 clinically stable patients with angiographically documented CHD, aged 40 to 68 years. Voluntary blood donors (n = 479) matched for age and gender served as controls. High-sensitivity C-reactive protein, serum amyloid A, plasminogen activator inhibitor-1 activity, von Willebrand factor, fibrinogen, plasma viscosity, albumin, and neutrophils were determined. The severity of CHD was evaluated by 3 coronary scoring systems: the clinical 1- to 3-vessel disease score, the American Heart Association extension score (1 to 15 segments), and the Gensini score. All markers of inflammation were highly significantly elevated (all p <0.005) in patients with stable CHD compared with controls. After multivariable adjustment by means of logistic regression analysis, the association between CHD and fibrinogen, plasma viscosity, von Willebrand factor, and plasminogen activator inhibitor-1 activity remained substantial, whereas it decreased in high-sensitivity C-reactive protein, serum amyloid A, and neutrophils. The combination of > or = 2 markers of inflammation was associated with a strongly increased risk of CHD. No association between markers of inflammation and any of the coronary scores applied was found. These results document an independent association between most of the markers of inflammation and chronic CHD, even in clinically stable patients. The combination of several of these biochemical markers, i.e., the determination of an "inflammatory risk profile," may be useful to further stratify cardiovascular risk.     

Plasma fibrinogen explains much of the difference in risk of coronary heart disease between France and Northern Ireland. The PRIME study

The incidence of coronary heart disease is higher in Northern Ireland than in France. These differences have not been adequately explained. We have investigated the associations of plasma fibrinogen concentration and factor VII activity with the incidence of coronary heart disease in a prospective cohort study involving 10600 men aged 50-59 living in four regions (Lille, Strasbourg, and Toulouse in France, Belfast in Northern Ireland). Baseline fibrinogen and factor VII were measured in 9489 men free of coronary heart disease at entry (7167 in France and 2322 in Northern Ireland). Over 5 years of follow-up, 161 participants developed myocardial infarction (MI) or coronary death (100 in France and 61 in Belfast) and 151 developed angina pectoris (94 in France and 57 in Belfast). The risk of future coronary events was 1.9 times higher in Belfast than in France (95% confidence interval: 1.5-2.4). Baseline mean levels of fibrinogen were significantly higher in Belfast than in France and they were higher in participants who experienced coronary events compared with those who did not in both countries. The age-adjusted relative risk of coronary heart disease associated with a rise of one standard deviation in fibrinogen level was 1.56 (95% confidence interval: 1.29-1.95, P<0.0001) in the whole cohort. This association remained significant after adjustment for other cardiovascular risk factors (relative risk:1.36; 95% confidence interval: 1.14-1.68; P<0.0001). There was no clear geographical variation in factor VII and no significant association between factor VII levels and the risk of coronary events was observed. Classic risk factors explained 25% of the excess risk of coronary heart disease in Belfast compared with France, while fibrinogen alone accounted for 30%. These findings add to the epidemiological evidence that elevated fibrinogen is a major risk factor for coronary heart disease.     

Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease.

AIM: Unstable coronary artery disease (CAD) is a multifactorial disease involving both thrombotic and inflammatory processes. We have assessed the time-course and the influence of thrombin inhibitors on changes in fibrinogen and C-reactive protein levels, and their relation to myocardial ischaemia in unstable CAD. METHODS AND RESULTS: Three hundred and twenty patients were randomized to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor, or unfractionated heparin. There were no significant differences between the treatment groups in fibrinogen or C-reactive protein levels. Overall, the fibrinogen levels were significantly increased in the first 24-96 h and still elevated at 30 days. The C-reactive protein levels showed a more pronounced increase during the first 24-96 h, but then markedly decreased over 30 days. Troponin-positive compared to troponin-negative patients had higher fibrinogen and C-reactive protein levels up to 96 h, although there was an increase compared to pre-treatment levels in both groups. A high fibrinogen level (pre-treatment top tertile) was associated with an increased rate of death or myocardial (re-)infarction at 30 days, 13% vs 5.6%, P=0.03, and increased long-term mortality. A high C-reactive protein level was related to increased 30-day mortality, 4% vs 0%, P=0.01. CONCLUSION: Myocardial cell injury was related to a high degree of inflammation, only some of which is an acutephase response due to tissue damage. The rise in fibrinogen was sustained, which might reflect low grade inflammation with long-term risk of thrombosis. The transient elevation of C-reactive protein levels might indicate a propensity to a pronounced inflammatory response and is associated with increased mortality.     

C-reactive protein gene haplotypes and risk of coronary heart disease: the Rotterdam Study.

AIMS: C-reactive protein is associated with risk of cardiovascular disease. However, whether C-reactive protein is a marker of severity of cardiovascular disease or actually is involved in its pathogenesis remains unknown. We investigated the relation between C-reactive protein haplotypes, representing the comprehensive variation of the C-reactive protein gene, and coronary heart disease. METHODS AND RESULTS: The Rotterdam Study is a prospective population-based study among men and women aged 55 years and older. C-reactive protein was associated with risk of coronary heart disease, with a multivariable adjusted hazard ratio of 1.9 (95% CI 1.5-2.4) for the highest vs. the lowest quartile. Four C-reactive protein haplotypes were present with overall frequencies of 32.8, 31.7, 29.5, and 5.9%. C-reactive protein serum levels were significantly different according to C-reactive protein haplotypes. C-reactive protein haplotypes were not associated with coronary heart disease. CONCLUSION: Steady-state C-reactive protein serum level is influenced by C-reactive protein gene haplotypes. Although elevated C-reactive protein level has lately been found to be a consistent and relatively strong risk factor for cardiovascular disease, our study does not support that the common variation in the C-reactive protein gene has a large effect on the occurrence of coronary heart disease.     

Acute-phase proteins and Chlamydia pneumoniae infection: which one is more important in acute coronary syndrome?

Elevated levels of acute-phase proteins, a systemic marker for inflammation, predict coronary events; Chlamydia pneumoniae (C. pneumoniae) infection is associated with coronary atherosclerosis. The present study investigated whether inflammation or infection is involved in the pathogenesis of acute coronary syndrome (ACS) and which one has the more important role. The study group comprised 49 patients with angiographically diagnosed ACS, 48 cases of chronic coronary heart disease (CCHD), and 44 subjects with a normal coronary profile. The levels of serum C-reactive protein (CRP), fibrinogen and anti-C. pneumoniae IgG antibody were measured. The IgG antibody against C. pneumoniae was higher in the ACS and CCHD groups compared with the control group after adjusting for age and gender. The levels of CRP and fibrinogen were significantly increased in patients with ACS compared with controls and CCHD patients. Multiple stepwise logistic regression analysis revealed that C. pneumoniae IgG antibody is an independent risk factor for both ACS and CCHD (odds ratio 2.3 and 2.1, respectively), but the CRP level is a risk factor only for ACS (odds ratio 6.9). The inflammatory response, as indicated by acute-phase proteins, especially CRP, rather than C. pneumoniae infection, may contribute more to the clinical course of ACS.     

Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the Women's Health Initiative Observational Study

BACKGROUND: Increasing evidence supports a role for inflammation in the atherosclerotic process. The role of the leukocyte count as an independent predictor of risk of a first cardiovascular disease (CVD) event remains uncertain. Our objective was to describe the relation between the baseline white blood cell (WBC) count and future CVD events and mortality in postmenopausal women. METHODS: In this prospective cohort study set in 40 US clinical centers, the study population comprised 72 242 postmenopausal women aged 50 to 79 years, free of CVD and cancer at baseline, enrolled in the Women's Health Initiative Observational Study. Main outcome measures included incident fatal coronary heart disease (CHD), nonfatal myocardial infarction, stroke, and total mortality. RESULTS: At baseline, the mean +/- SD age of the women was 63 +/- 7.3 years, 84% were white, 4% had diabetes, 35% had hypertension, and 6% were current smokers. The mean WBC count was 5.8 +/- 1.6 x 10(9) cells/L. During a mean of 6.1 years of follow-up, there were 187 CHD deaths, 701 nonfatal myocardial infarctions, 738 strokes, and 1919 deaths from all causes. Compared with women with WBC counts in the first quartile (2.5-4.7 x 10(9) cells/L), women in the fourth quartile (6.7-15.0 x 10(9) cells/L) had over a 2-fold elevated risk for CHD death (hazard ratio, 2.36; 95% confidence interval, 1.51-3.68), after multivariable adjustment for age, race, diabetes, hypertension, smoking, hypercholesterolemia, body mass index, alcohol intake, diet, physical activity, aspirin use, and hormone use. Women in the upper quartile of the WBC count also had a 40% higher risk for nonfatal myocardial infarction, a 46% higher risk for stroke, and a 50% higher risk for total mortality. In multivariable models adjusting for C-reactive protein, the WBC count was an independent predictor of CHD risk, comparable in magnitude to C-reactive protein. CONCLUSIONS: The WBC count, a stable, well-standardized, widely available and inexpensive measure of systemic inflammation, is an independent predictor of CVD events and all-cause mortality in postmenopausal women. A WBC count greater than 6.7 x 10(9) cells/L may identify high-risk individuals who are not currently identified by traditional CVD risk factors.     

Inflammation and coagulation factors in persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia

Depression is associated with increased cardiovascular disease, but the underlying mechanisms are not well understood. This study examines associations of depressive symptoms with inflammation and coagulation factors in persons aged > 65 years. Blood samples were obtained from 4,268 subjects free of cardiovascular disease (age 72.4 +/- 5.5 years, 2,623 women). Inflammation markers were C-reactive protein (CRP), white blood cell (WBC) count, total platelet count, and albumin; coagulation factors included factors VIIc and VIIIc and fibrinogen. Depression was assessed with the Center for Epidemiologic Studies Depression scale, and states of energy depletion with a validated exhaustion index. Statistical adjustments were made for risk factors (age, sex, race, systolic blood pressure, smoking status, diabetes mellitus) and physical measures of frailty (isometric handgrip, timed 15-feet walk test, activity level). Depression was associated with elevated CRP (3.31 +/- 0.10 vs 3.51 +/- 0.21 mg/L), WBC (6.14 +/- 0.03 vs 6.43 +/- 0.11 10(6)/L), fibrinogen (319 +/- 1 vs 326 +/- 3 mg/dl), and factor VIIc (124.6 +/- 0.6% vs 127.2 +/- 1.3%; all p <0.05). Exhaustion also was related to elevated inflammation and coagulation markers (p < 0.05). Exhausted men had markedly elevated CRP levels (6.82 +/- 2.10 mg/L) versus nonexhausted men (3.05 +/- 0.16: p = 0.007). After adjustment for control variables, exhaustion remained associated with albumin (p = 0.033), fibrinogen (p = 0.017), CRP (p = 0.066), and WBC (p = 0.060), whereas associations of depressive symptoms with biochemistry measures lost statistical significance. Thus, depression and exhaustion are associated with low-grade inflammation and elevated coagulation factors in persons aged > 65 years.     

Relation of markers of inflammation (C-reactive protein, fibrinogen, von Willebrand factor, and leukocyte count) and statin therapy to long-term mortality in patients with angiographically proven coronary artery disease

We evaluated a possible interaction between statins and inflammation in 1,246 patients with angiographically diagnosed coronary artery disease. Four different inflammatory markers were determined: high, sensitive C-reactive protein (hs-CRP) (p = 0.001), fibrinogen (p = 0.006), von Willebrand factor (p = 0.006), and leukocyte count (p = 0.03); these levels were significantly higher among the 88 patients who died of cardiac causes during follow-up (median 2.9 years) than among survivors. In a multivariate backward stepwise Cox regression mode, only hs-CRP was evaluated to be a significant predictor of death from coronary artery disease. This prediction was lost in statin-treated patients. Compared with patients receiving statin medication, patients without statins did not have increased cardiac mortality (even when low-density lipoprotein [LDL] levels were >125 mg/dl) when hs-CRP levels were not elevated. In contrast, patients without statins and elevated hs-CRP (top quartile) had a 2.3-fold increase in risk for fatal coronary events, independent of LDL levels. In conclusion, only elevated hs-CRP was selected as an independent predictor of death. Statin therapy is associated with elevated hs-CRP, with a risk reduction for fatal coronary events, independent of LDL levels; this, in part, may be explained by the anti-inflammatory effects on atherosclerosis.     

Ischemic cardiopathy: inflammation markers and the cardiovascular risk

In recent years it has been established that inflammation is a key mechanism in the pathogenesis of atherosclerosis and in coronary artery disease progression. Inflammation is a host response to a wide variety of tissue injuries. A persistent or continually repeated insult will lead to chronic inflammation which may result in tissue destruction and/or loss of normal organ function. Atherosclerosis and other pathologies involving inflammation are associated with increased levels of cytokines, which in turn raise acute-phase proteins levels in blood (acute inflammation markers, i.e. fibrinogen and C-reactive protein). It has been shown recently that concentrations of these proteins are higher in individuals at increased risk of developing cardiac events in the years to come. This is true both in apparently healthy men and women and in ischaemic heart disease patients. CRP is currently the inflammatory marker which appears to have captured the investigators' attention around the globe. In this report we review the current data on the relationship between atherosclerosis and inflammation, with special attention to cytokines and acute phase reactants. The use of acute phase reactants as prognostic risk markers in ischaemic heart disease is also discussed.     

Joint effects of C-reactive protein and other risk factors on acute coronary events

BACKGROUND: Elevated serum C-reactive protein (CRP) is a predictor of coronary heart disease in population samples. We studied the contribution of the simultaneous presence (joint effects) of elevated CRP and the classic as well as some new risk factors on acute coronary events. METHODS: With a nested case-control design and logistic regression analyses, we measured baseline and pre-event CRP levels in patients who had myocardial infarction or coronary death (cases) during an 8.5-year follow-up in the Helsinki Heart Study, a coronary primary prevention trial in dyslipidemic middle-aged men. The control patients were participants remaining free of coronary events. RESULTS: Baseline and pre-event CRP levels were higher in cases than in control patients (4.4 vs 2.0 mg/L, P <.001 and 6.0 vs 3.6 mg/L, P <.001). The relative risk attributed to elevated CRP was 40% higher with chronic elevation (odds ratio [OR], 3.34) compared with high baseline (OR, 2.24) or pre-event (OR, 2.26) level only. Hypertension, low high-density lipoprotein cholesterol, and high leukocyte count increased the risk only marginally without simultaneous occurrence of high CRP, whereas the joint effects of CRP and these classic risk factors suggested additive effects on coronary risk. In contrast, high levels of immunoglobulin G-class antibodies to oxidized low-density lipoprotein and antiprothrombin antibodies as well as high total immunoglobulin G level increased the risk irrespective of CRP. CONCLUSIONS: Elevated CRP enhances the risks attributed to classic coronary risk factors.     

Erythrocyte sedimentation rate: a possible marker of atherosclerosis and a strong predictor of coronary heart disease mortality.

AIMS: Since atherosclerosis is a chronic inflammation and the erythrocyte sedimentation rate is an appropriate test for monitoring chronic inflammatory responses, we wanted to investigate whether the erythrocyte sedimentation rate might carry prognostic information on the risk of sustaining coronary heart disease events. METHOD: The erythrocyte sedimentation rate was determined in 2014 apparently healthy men aged 40-60 years during an extensive cardiovascular survey in 1972-75, and the test was repeated in an identical follow-up examination 7 years later. Cause-specific mortality and rates of non-fatal myocardial infarction were followed for 23 years. RESULTS: The erythrocyte sedimentation rate was strongly correlated with age, haemoglobin level, smoking status, total cholesterol level and systolic blood pressure. After adjusting for all these associations in multivariate Cox regression analyses, the erythrocyte sedimentation rate emerged as a strong short- and long-term predictor of coronary heart disease mortality, particularly in men who had developed angina pectoris and/or had a positive exercise ECG test at the second survey. Increases in non-coronary heart disease deaths and in non-fatal myocardial infarctions were only seen in the upper erythrocyte sedimentation rate range. CONCLUSIONS: The erythrocyte sedimentation rate is a strong predictor of coronary heart disease mortality, and appears to be a marker of aggressive forms of coronary heart disease. The erythrocyte sedimentation rate probably gives substantial information in addition to that given by fibrinogen on the risk of coronary heart disease death.