New and old cardiovascular risk factors: C-reactive protein, homocysteine, cysteine and von Willebrand factor increase risk, especially in smokers.

BACKGROUND: The relative importance of new risk factors for heart disease singly or in combination is uncertain. We assessed relationships between C-reactive protein, homocysteine, cysteine, von Willebrand factor, activated factor XII and stable heart disease, as well as interaction with established risk factors. METHODS: A case-control study of 260 cases of stable heart disease from the Irish component of the European Action on Secondary Prevention through Intervention to Reduce Events (EUROASPIRE) II cohort and 260 age, sex-matched controls. C-reactive protein, homocysteine, cysteine, von Willebrand factor, activated factor XII and conventional risk factors were assayed or recorded. Interaction effects between new and conventional factors were assessed using additive and multiplicative models. RESULTS: C-reactive protein, homocysteine, cysteine and von Willebrand factor were significantly higher in cases than controls. Comparing the top fifth with the bottom four-fifths showed independent associations between heart disease and C-reactive protein [odds ratio (OR) 1.79; 95% confidence interval (CI) 1.12-2.86; P = 0.01], cysteine (OR 2.00; 95% CI 1.25-3.20; P = 0.004), von Willebrand factor (OR, 3.0; 95% CI 1.9-4.8; P < 0.0001). For homocysteine, the association was independent comparing the top tenth to the bottom nine-tenths (OR 1.95; 95% CI 1.02-3.41; P = 0.04). Activated factor XII was not associated with risk. The association between C-reactive protein and disease was U-shaped and a graded association existed between homocysteine, cysteine, von Willebrand factor and disease. C-reactive protein, homocysteine, cysteine and von Willebrand factor considerably increased risk associated with other factors, particularly smoking. CONCLUSIONS: Independent associations exist between stable heart disease and C-reactive protein, homocysteine, cysteine and von Willebrand factor. Strong combined effects were observed between these and conventional risk factors, particularly smoking. Smoking cessation may profoundly reduce risk associated with other risk factors. We found no evidence of a relationship between activated factor XII and disease.     

Both vitamin B6 and total homocysteine plasma levels predict long-term atherothrombotic events in healthy subjects.

AIMS: The contribution of homocysteine and group B vitamins in determining cardiovascular risk is debated. We assessed the predictive value of total homocysteine (tHcy), vitamin B12, folate, and vitamin B6 on the long-term occurrence of coronary and cerebral atherothrombotic events in a nested case-control study. METHODS AND RESULTS: Within a cohort of 1021 healthy subjects (490 men and 531 women) recruited in 1987, 66 first-ever coronary and 43 first-ever cerebrovascular events were recorded at a 12-year follow-up (cases, n=109). A total of 109 control subjects (remaining free from events) were matched with cases according to age, sex, smoking, hypertension, dyslipidaemia, and body mass index. Serum samples obtained in 1987 at baseline were used to measure tHcy, folate, and vitamins B12 and B6, as well as C-reactive protein plasma concentrations. We found a significant graded association between tHcy levels and the risk of coronary and cerebrovascular events [odds ratio (OR) for uppermost vs. lowermost quartile=1.34, 95% CI 1.01-1.76)]. Folate and vitamin B12 did not significantly differ between cases and controls, but were negatively (P<0.01) correlated with tHcy. Vitamin B6 did not correlate with tHcy levels, but differed significantly between cases and controls: for subjects in the uppermost quartile vs. the lowermost quartile of vitamin B6, OR=0.69 (95% CI 0.49-0.98). For subjects in the lowermost quartile of vitamin B6 and the uppermost quartile of tHcy, OR=17.50 (95% CI 1.97, 155.59). Cases and controls were not different as to C-reactive protein. CONCLUSION: tHcy and plasma vitamin B6 are long-term independent risk factors for coronary and cerebrovascular events.     

Chlamydia pneumoniae,Helicobacter pylori and cytomegalovirus infections and the risk of peripheral arterial disease in young women

Sero-epidemiological case control studies have observed positive relations between infections with Chlamydia pneumoniae, Helicobacter pylori or cytomegalovirus (CMV) and the occurrence of coronary artery disease (CAD) and stroke. Moreover, positive relations between 'infection burden' and CAD and the role of inflammation have recently been described. However, the relations between infection, inflammation and the occurrence of peripheral arterial disease (PAD) have not been reported so far. We performed a multi-centre population-based case-control study, using serum samples of 228 young female PAD patients and 643 control women to determine IgG antibody titres and C-reactive protein. The odds ratios for PAD in women with serological evidence for infection with C. pneumoniae, H. pylori or CMV were 2.0 (95% CI; 1.3-3.1), 1.6 (95% CI; 1.1-2.2) and 1.6 (95% CI; 1.1-2.3), respectively. The cumulative number of infections was positively related to the risk of PAD; the odds ratio was 1.5 (95% CI; 1.0-2.4), 2.7 (95% CI; 1.6-4.4) and 3.5 (95% CI; 1.5-8.1) for women with one, two or three infections, respectively. This increased risk, related to the 'infection burden', was found again in the subgroup of women with a high CRP level, but not in the subgroup with a low CRP level. Infections might be a causal component in the development of PAD. The risk of PAD is not only related to a single pathogen in particular, but also to the cumulative number of infections. The positive relation between 'infection burden' and PAD was only found in women with a high CRP level, which indicates that inflammation might be involved in the process that leads to PAD.     

Underrecognized peripheral arterial disease in patients with acute coronary syndrome: prevalence of traditional and emergent cardiovascular risk factors

INTRODUCTION AND OBJECTIVES: Peripheral arterial disease (PAD) frequently coexists with coronary artery disease. Our objective was to determine the prevalence of traditional and emergent cardiovascular risk factors in patients with acute coronary syndrome (ACS), with or without PAD. PATIENTS AND METHOD: A prospective study of 141 consecutive patients (< 70 years old) admitted to our hospital with ACS was performed. PAD was diagnosed when the ankle-brachial index (ABI) was < or = 0.9. Traditional cardiovascular risk factors were evaluated. C-reactive protein, homocysteine, amyloid A, lipoprotein (a), fibrinogen, apolipoprotein A1, and apolipoprotein B100 serum levels, and microalbuminuria were measured. Specific genotypes were also determined. RESULTS: Patients were divided into two groups according to whether PAD was present (37 patients, 26% of total, ACS-PAD group) or absent (104 patients, ACS group). In the ACS-PAD group, patients were older, and diabetes and hypertension were significantly more common. Moreover, levels of C-reactive protein (3.1 mg/L vs 2.18 mg/L; P<.05), homocysteine (11.45 mmol/L vs 9.4 mmol/L; P<.01), amyloid A (5.2 mg/mL vs 3.7 mg/mL; P<.05), and microalbuminuria (4.89 mg/L vs 3.1 mg/L; P<.05) were significantly higher in this group. Logistic regression analysis showed that poorly controlled diabetes (OR = 6.3; 95% CI, 1.1-36.7), time-dependent tobacco exposure (OR = 1.5 per decade; 95% CI, 1.2-2.0), and high pulse pressure (OR = 1.9 per 10 mmHg; 95% CI, 1.3-2.7) were independent predictors of the presence of PAD. CONCLUSIONS: Several traditional and emergent cardiovascular risk factors were more prevalent in patients with acute coronary syndrome and peripheral arterial disease. Moreover, some factors were independent predictors of peripheral arterial disease.     

Relation of dietary fat and fiber to elevation of C-reactive protein

We examined the relation of dietary fiber, fat, and other dietary factors to levels of highly sensitive C-reactive protein (CRP) in 4,900 adult participants in the 1999 to 2000 National Health and Nutrition Examination Survey (NHANES 99-00), which was a cross-sectional study of a nationally representative sample of noninstitutionalized United States residents. After controlling for demographic factors, body mass index, smoking, alcohol consumption, exercise, and total caloric intake, subjects in the third and fourth highest quartiles of fiber consumption had a lower risk of elevated CRP (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.43 to 0.96; OR 0.58, 95% CI 0.38 to 0.88, respectively) compared with the lowest quartile. Saturated fat consumption was modestly associated with elevated CRP (third quartile: OR 1.58, 95% CI 1.02 to 2.44; fourth quartile 1.44, 95% CI 0.80 to 2.58). The findings suggest that inflammation may link dietary fiber and fat to cardiovascular disease.     

Independent determinants of second derivative of the finger photoplethysmogram among various cardiovascular risk factors in middle-aged men.

The second derivative of the finger photoplethysmogram (SDPTG) has been used as a non-invasive examination for arterial stiffness. The present study sought to elucidate independent determinants of the SDPTG among various cardiovascular risk factors in middle-aged Japanese men. The SDPTG was obtained from the cuticle of the left-hand forefinger in 973 male workers (mean age: 44+/-6 years) during a medical checkup at a company. The SDPTG indices (b/a and d/a) were calculated from the height of the wave components. Multiple logistic regression analyses revealed that the independent determinants of an increased b/a (highest quartile of the b/a) were age (odds ratio [OR]: 1.12 per 1-year increase, 95% confidence interval [CI]: 1.09-1.15), hypertension (OR: 1.65, 95% CI: 1.03-2.65), dyslipidemia (OR: 1.51, 95% CI: 1.09-2.09), impaired fasting glucose/diabetes mellitus (OR: 2.43, 95% CI: 1.16-5.07), and a lack of regular exercise (OR: 2.00, 95% CI: 1.29-3.08). Similarly, independent determinants of a decreased d/a (lowest quartile of the d/a) were age (OR: 1.11 per 1-year increase, 95% CI: 1.08-1.14), hypertension (OR: 3.44, 95% CI: 2.20-5.38), and alcohol intake 6 or 7 days per week (OR: 2.70, 95% CI: 1.80-4.06). No independent association was observed between the SDPTG indices and blood leukocyte count or serum C-reactive protein levels. In conclusion, the SDPTG indices reflect arterial properties affected by several cardiovascular risk factors in middle-aged Japanese men. The association between inflammation and the SDPTG should be evaluated in further studies.     

Procoagulant factors and the risk of myocardial infarction in young women

Abstract:  Objectives:  We investigated whether elevated levels of factor VIII, IX and XI is associated with myocardial infarction (MI) in young women. In addition, we studied ABO blood group, von Willebrand factor (VWF) and C-reactive protein (CRP). Methods and results:  We compared 200 women with MI before age 49 years with 626 controls from a population-based case–control study. Mean levels of factor VIII activity (VIII), von Willebrand factor antigen (VWF), factor IX activity (IX) were higher in patients (133, 134 and 132 IU/dL) than in controls (111, 107 and 120 IU/dL, respectively). Mean levels of factor XI (XI) were equal in patients (114 IU/dL) and controls (113 IU/dL). The odds ratio (OR) for MI for blood group non-O vs. O was 1.6 [95% confidence interval (CI) 1.1–2.3]. The OR adjusted for age, index year and area of residence for the highest quartile >150 IU/dL of factor VIII was 2.7 (95% CI 1.6–4.6), of VWF 4.7 (95% CI 2.3–9.7), of factor IX 2.6 (95% CI 1.3–5.4) and of factor XI 0.9 (95% CI 0.5–1.4), all compared with the lowest quartile <100 IU/dL. Conclusions:  Non-O blood group, high VWF, factor VIII and factor IX levels are associated with an increased risk of MI in young women, while high factor XI levels are not.     

Relationship of beta2-microglobulin to arterial stiffness in Japanese subjects.

Beta2-Microglobulin (beta2m) is related to inflammatory diseases, but there have been few reports of a relationship between beta2m and atherosclerosis. We have examined the influence of beta2m on brachial-ankle pulse wave velocity (baPWV) to clarify whether it is related to arterial stiffness. baPWV, beta2m, C-reactive protein (CRP), and conventional risk factors were measured in 614 males and 158 females. The adjusted means of baPWV were compared with the quartiles of beta2m, and significant differences in baPWV were observed across the quartiles of beta2m (p = 0.037). After being adjusted for potential confounders, quartile 4 of beta2m, quartile 4 of CRP, and the combination of high beta2m plus high CRP were significantly associated with a high value of PWV (quartile 4 of beta2m: odds ratio [OR] 2.53, 95% confidence interval [CI], 1.31-4.89; quartile 4 of CRP: OR 2.27, 95% CI, 1.18-4.34; high beta2m plus high CRP: OR 5.60, 95% CI, 2.38-13.2). These results suggest that beta2m is associated with an increase of arterial stiffness. Further studies are needed to clarify whether beta2m is related to atherosclerotic diseases, and whether the combination of beta2m and CRP measurement is a useful predictor for the development of atherosclerosis.     

Protective effects of serum bilirubin on peripheral vascular disease

Background: Bilirubin, with recently recognized antioxidant and anti-inflammatory activity, has emerged as a candidate for atheroprotection. We hypothesized that higher levels of bilirubin would reduce susceptibility to peripheral arterial disease (PAD). Methods and results: We analyzed 7,075 adults with data available on the ankle brachial index, serum total bilirubin level, and PAD risk factors in the National Health and Nutrition Examination Survey (1999 to 2004), a nationally representative cross-sectional examination of the United States population. A 0.1 mg/dL increase in bilirubin level was associated with a 6% reduction in the odds of PAD (OR 0.94 [95% CI 0.90 to 0.98]) after adjustment for age, gender, race/ethnicity, smoking status, diabetes, hypertension, hypercholesterolemia, chronic kidney disease, CRP, and homocysteine. This result was not dependent on bilirubin levels above the reference range, liver disease, or alcohol intake. The inverse association of bilirubin with PAD tended to be stronger among men (OR 0.90 [95% CI 0.85 to 0.96]) compared with women (OR 0.97 [95% CI 0.91 to 1.04]; P (interaction) = 0.05), and was stronger among active smokers (OR 0.81 [95% CI 0.73 to 0.90]) compared with non-smokers (OR 0.97 [95% CI 0.93 to 1.02]; P (interaction) < 0.01). Conclusions: Increased serum total bilirubin level is associated with reduced PAD prevalence. This result is consistent with the hypothesis that bilirubin is protective from PAD.     

The relation of C-reactive protein levels to total and cardiovascular mortality in older U.S. women

PURPOSE: To determine whether serum C-reactive protein levels, a sensitive indicator of inflammation, are associated with the risk of cardiovascular mortality among older women. METHODS: We conducted a case-cohort study within the Study of Osteoporotic Fractures, a population-based study involving 9,704 women aged > or = 65 years from four U.S. centers. We randomly selected 400 women from the entire cohort plus an additional random sample of 92 women from the 1,125 women in the cohort who had died during the first 6 years of follow-up. Baseline serum C-reactive protein levels were measured using a high-sensitivity immunoassay. Cause-specific mortality was ascertained by review of death certificates and hospitalization records. Multivariable Cox proportional hazards regression was used to determine the association between C-reactive protein levels and cardiovascular mortality. RESULTS: During 6 years of follow-up, 150 of the 492 women died, including 52 who died of cardiovascular disease. After adjusting for potential confounders, women with C-reactive protein levels in the highest quartile (>3.0 mg/L) had a 8.0-fold (95% confidence interval [CI]: 2.2 to 29) greater risk of cardiovascular mortality than those in the lowest quartile (< or = 1.0 mg/L). The association remained strong in women who did not smoke or take estrogen, and when early deaths were excluded. Women who smoked and whose C-reactive protein levels were above the first quartile had a very high risk of cardiovascular mortality (relative risk [RR] = 13; 95% CI: 3.4 to 47). C-reactive protein levels were not associated with noncardiovascular mortality (RR = 0.92; 95% CI: 0.4 to 2.1). CONCLUSION: C-reactive protein level was an independent predictor of cardiovascular mortality in older women.     

C-reactive protein levels and coronary artery disease incidence and mortality in apparently healthy men and women: the EPIC-Norfolk prospective population study 1993-2003

INTRODUCTION: Measurement of C-reactive protein (CRP) levels has been proposed as a useful marker to improve the prediction of future coronary artery disease (CAD) risk, but this notion has been challenged recently. METHODS AND RESULTS: We performed a prospective case-control study among apparently healthy men and women. The odds ratio (OR) for future CAD incidence was 2.49 (95% CI=2.02-3.08, p for linearity <0.0001) unadjusted, and 1.66 (95% CI=1.31-2.12, p for linearity <0.0001), after adjustment for classical cardiovascular risk factors, for top versus bottom quartile of the CRP distribution. Notably, the risk factor adjusted predictive value was substantially stronger for fatal CAD (OR=2.92, 95% CI=1.83-4.67, p for linearity <0.0001) than for non-fatal CAD (OR=1.25, 95% CI=0.93-1.66, p for linearity=0.06). CRP levels were among the strongest predictors of CAD incidence and mortality. CRP levels remained a statistically significant predictor of future CAD, even after adjustment for the Framingham risk score. CONCLUSIONS: In this British cohort with risk factor levels representative of a contemporary Western population, CRP concentration was among the strongest predictors of CAD incidence and mortality. We suggest that current guidelines on CRP measurement in clinical practice should be based on contemporary and representative populations.     

Dietary Glycemic Index and Glycemic Load in Relation to Atherosclerotic Stenosis of Carotid and Cardiovascular Risk Factors in Ischemic Stroke Patients

Aim: Glycemic index (GI) and glycemic load (GL) influence postprandi al glucose concentrations and insulin responses. This study aims to ascertain the connection between GI, GL, and carotid atherosclerotic stenosis and cardiovascular disease (CVD) risk factors.Methods: A total of 669 patients with ischemic stroke within 7 days were enrolled. GI and GL were assessed with a validated food frequency questionnaire from patients. Computed tomography angiography (CTA) was used for the evaluation of carotid atherosclerotic stenosis. Traditional risk factors such as total cholesterol, triglycerides, LDL-C, HDL-C, C-reactive protein, homocysteine, neutrophil to lymphocyte ratio (NLR), fasting plasma glucose, and hemoglobin A1c were measured. GI/GL and its association with CVD risk factors and carotid stenosis were explored with Spearman analysis and multivariable logistic regression, respectively.Results: The prevalence of carotid stenosis was 63.2% of all 669 participants. The mean value of GI/GL was 49.3/137. Spearman test did not detect significant relationships between GI/GL and CVD risk factors. In multivariable regression models, GI (4^th vs. 1^st quartile, OR = 2.11; 95% CI, 1.30–3.42) and GL (4^th vs. 1^st quartile, OR = 1.82; 95% CI, 1.12–2.96) were observed a significant association with carotid stenosis after adjustment for major confounding factors. The association between GL and carotid stenosis became more pronounced among yo ungers (4^th vs. 1^st quartile, OR = 2.42; 95% CI, 1.13–4.76) and women (4^th vs. 1^st quartile, OR = 3.81; 95% CI, 1.45–5.05).Conclusion: Higher GI and GL were positively associated with a higher degree of carotid stenosis in these Chinese cerebral infarction patients, especially in younger patients and women.     

Homocysteine, the cholesterol of the 21st century. Impact of hyperhomocysteinemia on patency and amputation-free survival after intervention for critical limb ischemia

PURPOSE: To assess the prevalence of hyperhomocysteinemia and determine any correlation to the clinical and technical outcome of peripheral arterial revascularization for critical limb ischemia (CLI). METHODS: Between October 1, 2002, and December 31, 2006, 953 revascularization procedures were performed for CLI in a high-volume tertiary referral vascular/endovascular unit. Fasting plasma homocysteine was accurately measured preoperatively in 225 patients (124 men; mean age 75.8 years, range 45-98), who formed the basis for the study. All patients had multilevel disease (TASC II C and D lesions), and 73% had single vessel runoff. Composite primary endpoints included primary, assisted primary, and secondary patency; amputation-free survival; and all-cause mortality. RESULTS: The prevalence of hyperhomocysteinemia was 30% [69 patients (36 men; mean age 78.2 years, range 53-93)]; most (88%) of the patients showed a mild elevation in homocysteine (13-20 micromol/L). Patients with hyperhomocysteinemia had significantly lower primary, assisted primary, and secondary patency rates at all intervals to 36 months (3.3%, 10.8%, and 11.2%, respectively; p<0.001) after the intervention compared to patients with normal homocysteine levels (50.8%, 54.6%, and 57.1%, respectively). The mean amputation-free survival was significantly lower for patients with hyperhomocysteinemia (54.8% versus 81.0%, p=0.008). Overall, 27% of the normal homocysteine group progressed to vessel occlusion compared to 65% of the hyperhomocysteinemia group (p<0.0001). There was no significant difference between groups with respect to 4-year cumulative all-cause mortality (p=0.331). In a multivariate logistic regression analysis, only a homocysteine level >13.0 micromol/L was found to be significantly associated with adverse outcomes, such as amputation (OR=3.4, 95% CI 1.27 to 9.01; p=0.015) and graft occlusion (OR=7.97, 95% CI 3.63 to 17.5; p<0.0001). CONCLUSION: Hyperhomocysteinemia appears to be an independent risk factor for the progression of vascular disease and is an adverse prognostic factor for CLI patients undergoing peripheral arterial revascularization.     

Homocysteine as a predictive factor for hip fracture in elderly women with Parkinson's disease

Purpose

Incidence of hip fractures among elderly patients with Parkinson’s disease is high. Recent studies have found that levodopa induces hyperhomocysteinemia in Parkinson’s disease. Hyperhomocysteinemia is considered to be a risk factor for osteoporotic fractures in elderly men and women. Very high plasma homocysteine levels are a feature of homocystinuria, characterized by the early onset of osteoporosis. To determine the association between plasma homocysteine concentration and the risk of hip fracture in Parkinson’s disease patients receiving levodopa, we prospectively studied a cohort of elderly women with Parkinson’s disease.

Methods

We studied 199 elderly women with Parkinson’s disease receiving levodopa therapy, from whom blood samples had been obtained to measure plasma homocysteine. Age-adjusted incidence rates of hip fractures were calculated for quartiles of plasma homocysteine concentrations. Cox proportional-hazard regression was used to calculate hazard ratios for quartiles of homocysteine values.

Results

The mean duration of follow-up was 4.9 years. Hip fractures occurred in 66 patients. The age-adjusted incidence rates per 1000 person-years for hip fractures, from the lowest to the highest quartile of plasma homocysteine levels, were 1.59 (95% confidence interval [CI], 1.01-2.24), 1.57 (95% CI, 0.98-2.19), 1.21 (95% CI, 0.61-1.72), and 26.98 (95% CI, 16.48-37.24). The risk of hip fractures was greater in the highest quartile than that in the lowest, and the risk was almost 2.4 times higher.

Conclusion

These findings suggest that the homocysteine concentration is an important risk factor for hip fractures in Parkinson’s disease patients receiving levodopa.     

Delayed hypersensitivity skin testing to mumps and Candida albicans antigens is normal in middle-aged HTLV-I- and-II-infected U.S. cohorts

It has been reported that human T cell lymphotropic virus (HTLV)-I-infected persons in Japan have decreased delayed hypersensitivity skin test reactivity to tuberculin purified protein derivative (PPD), but HTLV-I- or -II-infected persons do not generally develop opportunistic infections. We administered standardized intradermal testing with PPD, mumps, and Candida albicans antigens to 31 HTLV-I, 48 HTLV-II, and 143 seronegative subjects in the United States. Reactivity at 48 hr was compared among the three groups. Response rates to PPD were very low in all subjects. Fifty-five percent of seronegative subjects did not react to mumps antigen, compared with 55% of HTLV-I [adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.27-2.33] and 38% of HTLV-II (OR = 0.73, 95% CI 0.33-1.64). Fifty-one percent of seronegatives did not react to Candida albicans antigen, compared with 34% of HTLV-I (OR = 0.37, 95% CI 0.15-0.93) and 46% of HTLV-II (OR = 0.71, 95% CI 0.34-1.52). Anergy was present in 33% of seronegatives, 28% of HTLV-I (OR = 0.60, 95% CI 0.20-1.78), and 19% of HTLV-II (OR = 0.56, 95% CI 0.22-1.44). HTLV-I- and -II-infected persons appear to have intact delayed hypersensitivity skin test responses to mumps and Candida albicans antigens.     

Relationship of C-reactive protein levels with angiographic findings and markers of necrosis in non-ST-segment elevation acute coronary syndrome

INTRODUCTION AND OBJECTIVES: The mechanism responsible for elevated C-reactive protein levels (inflammation of the ruptured atherosclerotic plaque or myocardial necrosis) in acute coronary syndromes is controversial. The aim of this study was to investigate the relationship between C-reactive protein levels and angiographic complexity of the culprit lesion and troponin elevation in patients with non-ST elevation acute coronary syndromes. PATIENTS AND METHOD: The study group consisted of 125 patients with single-vessel disease. Troponin-I and C-reactive protein were measured, and the complexity of the culprit lesion was analyzed (TIMI flow and thrombus). Information on age, sex, smoking habit, hypertension, hypercholesterolemia and diabetes was obtained from the medical record. RESULTS: The quartile distribution of C-reactive protein showed more patients with TIMI flow < 3 (31%, 28%, 18%, and 55%; P=.02), thrombus (3%, 6%, 7%, and 28%; P=.007) and troponin-I elevation (19%, 44%, 50%, and 66%; P=.003) in the fourth quartile. Multivariate analysis showed both thrombus (OR = 4.1; 95% CI, 1.2-14.3; P=.03) and troponin elevation (OR = 2.6; 95% CI, 1.1-6.3; P=.03) to be associated with C-reactive protein > 18 mg/L (fourth quartile cut-off). When treated as a continuous variable, higher levels of C-reactive protein were also associated with thrombus (P=.02) and troponin elevation (P=.003). No other clinical variables were related with C-reactive protein levels. CONCLUSIONS: Both angiographic complexity of the culprit lesion and elevated troponin level are related with increased C-reactive protein levels in non-ST elevation acute coronary syndromes.     

Relation of inflammation to peripheral arterial disease in the national health and nutrition examination survey, 1999-2002

The relation between inflammation and peripheral arterial disease (PAD) is not well characterized. This study examined this relation and its consistency across important subgroups in a cross-sectional, nationally representative sample of the adult United States population. C-reactive protein (CRP), fibrinogen, leukocyte count, and PAD were assessed in a sample of 4,787 participants aged>or=40 years in the National Health and Nutrition Examination Survey 1999-2002. PAD was defined as an ankle-brachial blood pressure index <0.9. Graded relations were present between inflammatory markers and PAD. The multivariate adjusted odds ratios of PAD associated with the highest versus the lowest quartile of CRP, fibrinogen, and leukocyte count were 2.14 (95% confidence interval [CI] 1.41 to 3.25), 2.49 (95% CI 1.27 to 4.85), and 1.67 (95% CI 0.84 to 3.31), respectively (each p trend<0.05 across quartiles). Associations between inflammation and PAD were similar across gender, obesity, and diabetic subgroups. However, the odds ratios of PAD for the highest CRP quartile versus the 3 lowest quartiles were 3.10 (95% CI 1.76 to 5.45) for non-Hispanic blacks versus 1.50 (95% CI 0.98 to 2.28) for non-Hispanic whites and 1.11 (95% CI 0.57 to 2.17) for Mexican Americans (p interaction=0.049) and 5.59 (95% CI 1.82 to 17.17) for patients aged 40 to 54 years versus 2.01 (95% CI 1.13 to 3.58) for patients aged 55 to 69 years and 0.98 (95% CI 0.65 to 1.48) for patients aged>or=70 years (p interaction=0.018). Odds ratios of PAD for the highest fibrinogen quartile versus the lowest 3 quartiles were 3.26 (95% CI 1.69 to 6.28) for current smokers versus 0.83 (95% CI 0.51 to 1.35) for never smokers (p interaction=0.006). In conclusion, in the general United States adult population, inflammation is independently associated with PAD.     

Hyperhomocysteinemia is an independent risk factor in young patients with coronary artery disease in southern China

Background

Elevated plasma homocysteine (Hcy) is considered to be a risk factor of coronary artery disease (CAD), although this is still controversially discussed. This study investigated the role of Hcy in young patients with CAD in southern China.

Methods

A total of 146 consecutive patients (aged ≤?55 years) with angiographically proven CAD were enrolled in the study and 138 age-matched non-CAD individuals were included as the control group. Hcy levels were measured by enzymatic assay. Hyperhomocysteinemia (HHcy) was defined as Hcy ≥?15 µmol/l. A 10-year CAD risk was calculated using the Framingham risk score (FRS) modified according to the National Cholesterol Education Program Adult Treatment Panel III.

Results

There were significant differences between the CAD and control groups with regard to male sex (P?<?0.01), smoking history (P?<?0.05), and triglyceride levels (TG, P?<?0.05), but no remarkable difference in other conventional risk factors (all P?>?0.05). Hcy and high-sensitivity C-reactive protein (hs-CRP) levels were significantly higher in the CAD group than those in the control group (both P?<?0.05). The FRS and estimated 10-year absolute CAD event risk were low in both groups and did not show a statistical difference. Multivariate logistic regression showed that male sex (odds ratio, OR, 3.68; 95?% confidence interval, 95?% CI, 1.54–10.01), smoking (OR, 2.54; 95?% CI, 1.15–5.36), TG (OR, 1.30; 95??% CI, 1.08–3.06), hs-CRP (OR, 3.74; 95?% CI, 1.72–12.21), and HHcy (OR, 2.03; 95?% CI, 1.26–5.83) were independently correlated with CAD in young patients.

Conclusion

HHcy is an important independent risk factor for CAD in young patients in southern China after adjusting for other risk factors.     

Plasma N-terminal pro-B-type natriuretic peptide for prediction of death or nonfatal myocardial infarction following percutaneous coronary intervention

B-type natriuretic peptide (BNP) and the N-terminus of pro-BNP (NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of baseline NT-pro-BNP alone or in combination with C-reactive protein (CRP) for clinical outcome after percutaneous coronary intervention (PCI). Within a single center registry of contemporaneous PCI, we investigated the prognostic value of baseline plasma NT-pro-BNP and CRP concentrations for the prediction of death or nonfatal myocardial infarction (MI) during 12 to 14 months of follow-up. Among 1,172 consecutive patients, the occurrence of death or MI increased significantly with baseline NT-pro-BNP before PCI (first quartile 0 of 294, second quartile 6 of 291 [2.1%], third quartile 4 of 294 [1.4%], fourth quartile 22 of 293 [7.5%)]; p <0.0001). NT-pro-BNP in the top quartile significantly predicted death (odds ratio [OR] 13.37, 95% confidence interval [CI] 4.50 to 40.38, p <0.0001) and was associated with nonfatal MI (OR 2.53, 95% CI 0.77 to 8.34, p = 0.22) An abnormal CRP was significantly associated with death (OR 3.47, 95% CI 1.26 to 9.54, p = 0.019). Stepwise multivariate logistic regression analysis identified age >65 years and NT-pro-BNP as independent significant predictors of death/MI (age OR 3.18, 95% CI 1.32 to 7.67, p = 0.01; NT-pro-BNP OR 4.57, 95% CI 2.07 to 10.10, p = 0.0001). Baseline NT-pro-BNP before PCI provides important, independent prognostic information for the occurrence of death or nonfatal MI during long-term follow-up.     

Lipoprotein-associated phospholipase A2, hormone use, and the risk of ischemic stroke in postmenopausal women

Few studies have investigated the role of elevated lipoprotein-associated phospholipase A2 (Lp-PLA(2)) with stroke risk, and those that have are based on small numbers of strokes. No study has evaluated the effect of hormone therapy use on the association of Lp-PLA(2) and stroke. We assessed the relationship between Lp-PLA(2) and the risk of incident ischemic stroke in 929 stroke patients and 935 control subjects in the Hormones and Biomarkers Predicting Stroke Study, a nested case-control study from the Women's Health Initiative Observational Study. Mean (SD) levels of Lp-PLA(2) were significantly higher among case subjects (309.0 [97.1]) than control subjects (296.3 [87.3]; P<0.01). Odds ratio for ischemic stroke for the highest quartile of Lp-PLA(2), compared with lowest, controlling for multiple covariates, was 1.08 (95% CI: 0.75 to 1.55). However, among 1137 nonusers of hormone therapy at baseline, the corresponding odds ratio was 1.55 (95% CI: 1.05 to 2.28),whereas there was no significant association among 737 hormone users (odds ratio: 0.70; 95% CI: 0.42 to 1.17; P for interaction=0.055). Moreover, among nonhormone users, women with high C-reactive protein and high Lp-PLA2 had more than twice the risk of stroke (odds ratio: 2.26; 95% CI: 1.55 to 3.35) compared with women low levels in both biomarkers. Furthermore, different stroke cases were identified as high risk by Lp-PLA(2) rather than by C-reactive protein. Lp-PLA(2) was associated with incident ischemic stroke independently of C-reactive protein and traditional cardiovascular risk factors among nonusers of hormone therapy with highest risk in those who had both high C-reactive protein and high Lp-PLA(2).