Soluble Intercellular Adhesion Molecule Type Research Articles

Is analysis of inflammatory biomarkers and lymphocyte subpopulations useful in prediction of tuberculosis treatment outcomes?

Analysis of inflammatory biomarkers and lymphocytes during the treatment of tuberculosis (TB) could yield findings that influence the routine clinical practice and use of new anti-TB drugs. This study aimed to evaluate whether the selected biomarkers—soluble intercellular adhesion molecule type 1, soluble urokinase-type plasminogen activator receptor (suPAR), and C-reactive protein (CRP)—and T-cell subpopulations are useful for predicting culture conversion, treatment outcomes, and the extent of radiological lesions (calculated using X-ray score) in patients with drug-sensitive pulmonary TB. This study included 62 patients with drug-sensitive pulmonary TB. CRP and suPAR levels significantly decreased after 1 month of treatment. Before treatment initiation, CRP and suPAR levels were significantly higher in patients without culture conversion; however, none of the selected host biomarkers appeared to significantly influence the conversion status or treatment outcomes. Some lymphocyte subpopulations were correlated with X-ray scores before TB treatment initiation, but lung destruction, as determined using X-ray scores, showed the highest correlation with the baseline CRP value. We conclude that selected host biomarkers have a very limited role in predicting TB treatment outcomes and culture conversion and do not appear to be superior to CRP in monitoring TB treatment.

Prevalence of dynapenic obesity and sarcopenic obesity and their associations with cardiovascular disease risk factors in peritoneal dialysis patients.

BackgroundDynapenic obesity and sarcopenic obesity increase cardiovascular disease (CVD) and mortality in nonuremic patients. The present study was designed to determine the prevalence of dynapenic obesity and sarcopenic obesity and their associations with CVD risk factors in peritoneal dialysis (PD) patients.MethodsAll eligible PD patients in Tehran peritoneal dialysis centers were included in this cross-sectional study. Skeletal muscle mass and fat mass were assessed using bioelectrical impedance analysis. Muscle strength and physical performance were determined using hand grip strength and a 4-meter walk gait speed test, respectively. In addition, a 5-mL blood sample was obtained from each patient.ResultsThe prevalence of dynapenic obesity and sarcopenic obesity were 11.4% and 3.8% in PD patients, respectively. Serum high-sensitive C-reactive protein (hs-CRP), soluble intercellular adhesion molecule type 1, triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly higher in PD patients with dynapenic obesity than in dynapenic nonobese and nondynapenic nonobese patients. Similarly, serum concentrations of CVD risk factors in PD patients with sarcopenic obesity were higher than in nonsarcopenic nonobese patients, but these differences were statistically significant only for serum hs-CRP and triglyceride. In addition, muscle strength and skeletal muscle mass percentage were negatively associated with markers of inflammation and dyslipidemia, whereas body fat percentage was positively associated with these CVD risk factors.ConclusionThis study indicates that although the prevalence of dynapenic obesity and sarcopenic obesity are relatively low in PD patients, these disorders may be associated with CVD risk factors.

Effect of Synbiotic and Probiotic Supplementation on Serum Levels of Endothelial Cell Adhesion Molecules in Hemodialysis Patients: a Randomized Control Study.

The aim of this study was to investigate the effect of synbiotic and probiotic supplementation on serum vascular dysfunction and necrosis markers in hemodialysis (HD) patients. In this randomized, double-blind, placebo-controlled trial, 75 HD patients were randomly assigned to either the synbiotic or probiotic or placebo group. The patients in the synbiotic group received 15g of prebiotics and 5g probiotic powder containing Lactobacillus acidophilus strain T16 (IBRC-M10785), Bifidobacterium bifidum strain BIA-6, Bifidobacterium lactis strain BIA-6, Bifidobacterium longum strain LAF-5 (2.7 × 107CFU/g each) in sachets (n = 25), whereas the probiotic group received 5g probiotics same to the first group with 15g of maltodextrin powder in sachets (n = 25) and the placebo group received 20g of maltodextrin powder in sachets (n = 25) for 12weeks. At baseline and the end of the study, serum concentrations of soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), cytokeratin 18 (CK-18) as the necrosis marker, uric acid, and phosphate levels were measured. Feces also were collected for microbiota colony counting. Serum ICAM-1 level reduced significantly in the synbiotic group after the intervention period (P = 0.02), and this reduction was significantly different in the synbiotic group in comparison to the placebo group (P = 0.03). Serum levels of VCAM-1 and CK-18 were not significantly different between the groups. However, the reduction in serum levels of VCAM-1 in the synbiotic group was significantly higher in comparison to the placebo group (P = 0.01). Multivariate linear regression analysis revealed that ∆ phosphate was the sole independent determinant of ∆ICAM-1 (P = 0 < 001). The study indicated that synbiotic supplementation reduced serum ICAM-1 level, which is a risk factor for cardiovascular diseases in HD patients, but has no effect on the necrosis marker. Trial registration: www.irct.ir (IRCT2017041233393N1).

Pomegranate Juice Increases Sirtuin1 Protein in Peripheral Blood Mononuclear Cell from Patients with Type 2 Diabetes: A Randomized Placebo Controlled Clinical Trial.

Few studies have examined anti-inflammatory effects of pomegranate juice (PJ). The present study aimed to evaluate the effect of PJ on nuclear factor kappa B (NF-κB) p65 and sirtuin1 in peripheral blood mononuclear cell (PBMC), and plasma vascular inflammation biomarkers. Patients with type 2 diabetes were randomly assigned to either the PJ (n = 22) or the placebo group (n = 22). The patients in the PJ group received 250 mL of PJ daily for 12 weeks, whereas the placebo group received corresponding control beverages of similar color and energy content. At baseline and at the end of week 12, fasting plasma concentrations of soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and soluble E-selectin (sE-selectin) were measured. NF-κB p65 and SIRT1 were measured in the PBMC. Plasma sE-selectin concentration decreased significantly in the PJ group at the end of week 12 compared to baseline (P < 0.001 for treatment effect), and the reduction was significant in comparison with the placebo group (P < 0.05 for treatment effect). There were no significant differences between the two groups in plasma sICAM-1 and sVCAM-1. At the end of the study, compared with the placebo group, NF-κB p65 in PBMC was significantly lower (P < 0.01 for treatment effect) and SIRT1 was significantly higher (P < 0.0001 for treatment effect) in the PJ group. This study supports the PJ consumption as a food with potential benefits in individuals with type 2 diabetes as evidenced by improvements in NF-κB and SIRT1 levels in PBMC of study participants.

Effects of ginger on serum glucose, advanced glycation end products, and inflammation in peritoneal dialysis patients

ObjectiveThe aim of this study was to investigate the effects of ginger supplementation on serum glucose, advanced glycation end products, oxidative stress, and systemic and vascular inflammatory markers in patients on peritoneal dialysis (PD). MethodsIn this randomized, double-blind, placebo-controlled trial, 36 patients on PD were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 1000 mg/d ginger for 10 wk, whereas the placebo group received corresponding placebos. At baseline and the end of week 10, serum concentrations of glucose, carboxymethyl lysine, pentosidine, malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and sE-selectin were measured after a 12- to 14-h fast. ResultsSerum fasting glucose decreased significantly up to 20% in the ginger group at the end of week 10 compared with baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum carboxymethyl lysine, pentosidine, MDA, hs-CRP, sICAM-1, sVCAM-1, and sE-selectin. ConclusionThis study indicated that daily administration of 1000 mg ginger reduces serum fasting glucose, which is a risk factor for hyperinsulinemia, dyslipidemia, peritoneal membrane fibrosis, and cardiovascular disease, in patients on PD.

Association of malnutrition-inflammation score, dialysis-malnutrition score and serum albumin with novel risk factors for cardiovascular diseases in hemodialysis patients

Background: This study was designed to investigate the associations between malnutrition-inflammation score (MIS), dialysis-malnutrition score (DMS) and serum albumin with novel risk factors for cardiovascular diseases (CVD) in hemodialysis (HD) patients. Methods: In this cross-sectional study, 291 HD patients were randomly selected from among 2302 adult HD patients in Tehran HD centers. The MIS and DMS were determined during one of the dialysis sessions in these patients. In addition, 4 mL blood was obtained before dialysis and analyzed for serum albumin and novel risk factors for CVD, including C-reactive protein (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), endothelin-1 and lipoprotein (a) [Lp (a)]. Results: MIS and DMS were significantly positively correlated with serum CRP (p < 0.01) and sICAM-1 (p < 0.01), whereas serum albumin concentration was significantly negatively correlated with serum CRP (p < 0.01) and sICAM-1 (p < 0.01). There were no significant correlations between MIS, DMS and serum albumin with serum concentrations of sVCAM-1, sE-selectin, MDA, NO, endothelin-1 and Lp (a). Conclusion: This study indicates that protein-energy wasting indicators in HD patients are associated with serum CRP and sICAM-1, as two CVD risk factors.

Genetic Determinism of the Functional Condition of the Endothelium in Patients with Chronic Diffuse Liver Diseases and Disorders of Thyroid Homeostasis

Patients with chronic diffuse of liver disease have a violation of thyroid homeostasis in the form of reduction of free triiodothyronine in the blood serum, as well as thyroid stimulating hormone increasing content and of free thyroxin.In patients with chronic diffuse liver diseases there is a relation between the expression of Pro197Leu polymorphism of GPX1 gene and indices of cellular adhesion, which is revealed by a reliably higher content of soluble intercellular adhesion molecule type 1 in the blood serum in homozygotic carriers of Leu-allele. Changes of the endothelial functional state in patients with chronic diffuse liver diseases are associated with Pro197Leu polymorphism of GPX1 gene, which is proved by a reliably higher index of desquamated endotheliocytes amount and lower level of nitric oxide metabolites in the carriers of LeuLeu-genotype.

RELATIONSHIP BETWEEN SERUM SOLUBLE CELLULAR ADHESION MOLECULES CONCENTRATION AND CHOLESTEROL AND LIPOPROTEINS IN PATIENTS REFERRED TO ATHEROSCLEROSIS

ObjectivesEvidence is emerging that serum soluble cellular adhesion molecules contributes to the development and progression of atherosclerosis and cardiovascular disease. Little is known, however, regarding an association between soluble cellular...

Effects of Marine Omega-3 Fatty Acids on Serum Systemic and Vascular Inflammation Markers and Oxidative Stress in Hemodialysis Patients

Background and Aims: High concentrations of serum inflammation markers, especially vascular inflammation markers, are an important risk factor for cardiovascular diseases in hemodialysis patients. The present study was designed to investigate the effects of marine omega-3 fatty acids on serum systemic and vascular inflammation markers and oxidative stress in hemodialysis patients. Methods: Thirty-four hemodialysis patients were randomly assigned to either the marine omega-3 fatty acid or the placebo group. Patients in the omega-3 fatty acid group received 2,080 mg marine omega-3 fatty acids daily for 10 weeks, whereas the placebo group received a corresponding placebo.At baseline and the end of week 10, 5 ml blood was collected after a 12- to 14-hour fast. Results: Mean serum soluble intercellular adhesion molecule type 1 (sICAM-1) decreased significantly in the omega-3 fatty acid group at the end of week 10 compared to baseline (p < 0.05) and this reduction was significant in comparison with the placebo group (p < 0.05). No significant differences were observed between the two groups in mean changes in serum soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, C-reactive protein, interleukin-6, tumor necrosis factor-α, malondialdehyde and total antioxidant capacity. Conclusion: The results of the present study indicate that marine omega-3 fatty acids can reduce serum sICAM-1, a risk factor for cardiovascular diseases, but it has no effect on serum systemic inflammation markers and oxidative stress in hemodialysis patients.

Effects of l-carnitine Supplement on Serum Amyloid A and Vascular Inflammation Markers in Hemodialysis Patients: A Randomized Controlled Trial

We studied the effects of l-carnitine supplement on serum amyloid A (SAA), a systemic inflammation marker, and vascular inflammation markers in hemodialysis patients. This was a randomized, double-blind, placebo-controlled trial. The study was performed in Soodeh Hemodialysis Center in Islamshahr, Iran. We included 36 hemodialysis patients (15 men and 21 women). The patients on hemodialysis were randomly assigned to either a carnitine or a placebo group. Patients in the carnitine group received 1,000 mg/day oral l-carnitine for 12 weeks, whereas patients in the placebo group received a corresponding placebo during the study. Serum free carnitine, SAA, soluble intercellular adhesion molecule type 1, soluble intercellular adhesion molecule type 2, soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, and oxidized low-density lipoprotein were measured at baseline and at the end of week 12 of the study. Mean serum free carnitine concentration increased significantly to 150% of baseline in the carnitine group at the end of week 12 (P < .001), whereas serum SAA showed a significant 32% decrease (P < .001). No significant changes were observed in the serum concentrations of free carnitine and SAA in the placebo group during the study. There were no significant differences between the two groups in mean changes in serum soluble intercellular adhesion molecule type 1, soluble intercellular adhesion molecule type 2, soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, and oxidized low-density lipoprotein concentrations. The study indicates that l-carnitine supplement reduces serum SAA, which is a risk factor for cardiovascular diseases in hemodialysis patients, but has no effect on vascular inflammation markers.

Correlação entre mediadores inflamatórios na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior por vírus sincicial respiratório e a gravidade da doença

To determine whether the concentrations of inflammatory mediators (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-alpha, IL-6 and IL-10) in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) correlate with the clinical markers of disease severity. Between July of 2004 and December of 2005, 30 children less than three months of age, diagnosed with LRTI caused by RSV and admitted to a neonatal ICU, were included in this study. The severity of disease at hospital admission, as determined with a modified clinical scoring system, presented a significant positive correlation with sICAM-1 and IL-10 concentrations in the nasopharyngeal secretion, as well as with IL-6 concentrations in the serum, of the patients. In addition, serum IL-6 concentrations presented a significant positive correlation with the duration of oxygen therapy and with the length of hospital stay. At hospital admission, the concentrations of sICAM-1 and IL-10 in the nasopharyngeal secretion, as well as the concentration of IL-6 in the serum, could be used as markers of severity in patients with LRTI caused by RSV. The serum levels of IL-6 determined at admission could also be used to predict prolonged oxygen supplementation and hospital stay.

Inhibition of tumour necrosis factor alpha in idiopathic membranous nephropathy: a pilot study

Tumour necrosis alpha has been implicated in the pathogenesis of autoimmune disorders was to evaluate the safety, tolerability and potential efficacy of the tumour necrosis factor alpha (TNF-alpha) inhibitor, etanercept (ET), in patients with idiopathic membranous nephropathy (MN). Patients with biopsy-proven MN, nephrotic-range proteinuria and clearance of creatinine 50 ml/min or more were included in the study. Exclusion criteria were treatment with steroids or cyclosporine during the previous 3 months, or cytotoxic agents within 6 months prior to entry. ET was administered subcutaneously, 25 mg twice per week for 3 months. Plasma levels of TNF-alpha, interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), soluble intercellular adhesion molecule type 1 (sICAM-1), E-selectin, and the soluble form of tumour necrosis factor receptor-55 (sTNFR-55) were measured on entry and at Months 3, 6, and 9 after commencing therapy. Twelve patients were entered in the study (four females/eight males, mean time from diagnosis 8.3 months). The therapy was well tolerated; no infections or other adverse events were recorded by the end of follow-up. Two patients exhibited complete remission of proteinuria for at least 4 years. No significant change was found in the levels of TNF-alpha, IL-1, IL-6, IL-8 and IL-10 during the study. Similarly the levels of E-selectin and sICAM-1 were not significantly altered by therapy. Although we found no change in sTNFR-55 at 3 and 6 months, the levels of sTNFR-55 were found significantly decreased 9 months after therapy (mean difference from baseline: 334 +/- 527 pg/ml, P = 0.028). Short-term use of ET in a small series of patients reduced sTNFR-55 levels but did not exhibit any significant clinical effect in the majority of patients.

Circulating Markers of Endothelial Dysfunction Interact With Proteinuria in Predicting Mortality in Renal Transplant Recipients

Proteinuria is associated with endothelial dysfunction (ED) and increased mortality. We investigated whether urinary protein excretion (UPE) is correlated with markers of ED and whether these markers affect the association of proteinuria with mortality in renal transplant recipients (RTR). Six hundred four RTR with a functioning graft for more than 1 year were included. RTR were divided according to UPE: less than 0.3, 0.3 to 1.0, and more than 1.0 g/24 hr. Soluble intercellular adhesion molecule type 1 (sICAM-1) and soluble vascular cellular adhesion molecule type 1 (sVCAM-1) were measured using ELISA. UPE (0.2 [0.0-0.5] g/24 hr), sICAM-1 (603 (514-721) ng/mL), and sVCAM-1 (952 [769-1196] ng/mL) were measured at 6.0 (2.6-11.4) years posttransplant. During follow-up for 5.3 (4.7-5.7) years, 94 (16%) RTR died. UPE was correlated with sVCAM-1 (standardized beta=0.13, P=0.001) but not with sICAM-1 (standardized beta=0.04, P=0.3). RTR with UPE more than 1.0 g/24 hr and high sICAM-1 (hazard ratio=4.7, 95% confidence interval 2.3-9.7, P<0.0001) or sVCAM-1 (hazard ratio=4.2, 95% confidence interval 2.0-8.6, P=0.0001) concentrations were at increased risk for death, whereas RTR with UPE more than 1.0 g/24 hr and low concentrations of sICAM-1 and sVCAM-1 were not. In RTR, UPE is correlated with sVCAM-1 but not with sICAM-1. Furthermore, RTR with proteinuria and high concentrations of sICAM-1 or sVCAM-1 have an increased risk for death, compared with RTR without proteinuria, whereas this is not the case in RTR with proteinuria but low concentrations of sICAM-1 and sVCAM-1. These results suggest that ED plays a role in the association of proteinuria with mortality after renal transplantation.

Tu-P7:105 Selected markers of inflammation, past chlamydia pneumoniae infection in patients with stable angina pectoris, without traditional risk factors

The aim of this study was to investigate the effects of ginger supplementation on serum glucose, advanced glycation end products, oxidative stress, and systemic and vascular inflammatory markers in patients on peritoneal dialysis (PD).In this randomized, double-blind, placebo-controlled trial, 36 patients on PD were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 1000 mg/d ginger for 10 wk, whereas the placebo group received corresponding placebos. At baseline and the end of week 10, serum concentrations of glucose, carboxymethyl lysine, pentosidine, malondialdehyde (MDA), high-sensitivity C-reactive protein (hs-CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and sE-selectin were measured after a 12- to 14-h fast.Serum fasting glucose decreased significantly up to 20% in the ginger group at the end of week 10 compared with baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum carboxymethyl lysine, pentosidine, MDA, hs-CRP, sICAM-1, sVCAM-1, and sE-selectin.This study indicated that daily administration of 1000 mg ginger reduces serum fasting glucose, which is a risk factor for hyperinsulinemia, dyslipidemia, peritoneal membrane fibrosis, and cardiovascular disease, in patients on PD.

Effect of Intensive Glycemic Control on Levels of Markers of Inflammation in Type 1 Diabetes Mellitus in the Diabetes Control and Complications Trial

Type 1 diabetes mellitus is associated with an increased risk of cardiovascular disease (CVD) that is not fully explained by conventional risk factors. The Diabetes Control and Complications Trial (DCCT) showed that intensive diabetes therapy reduced levels of LDL cholesterol and triglycerides but increased the risk of major weight gain, which might adversely affect CVD risk. The present study examined the effect of intensive therapy on levels of several markers of inflammation that have been linked to risk of CVD. We measured levels of inflammatory biomarkers in stored baseline and 3-year follow-up serum specimens from a random sample of 385 participants in the DCCT, a multicenter trial in which 1441 subjects aged 13 to 39 years with type 1 diabetes mellitus were randomized to intensive or conventional diabetes treatment. The markers included high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), and the 55-kDa soluble tumor necrosis factor-alpha receptor 1 (sTNF-R1). We examined the effect of intensive therapy on the change in levels of the inflammatory markers. In unadjusted analyses, levels of hsCRP and sTNF-R1 increased in both treatment groups after 3 years of follow-up, with no significant difference between groups for hsCRP (P=0.53) but with a greater increase of sTNF-R1 in the intensive therapy group (P=0.002). In contrast, mean levels of sICAM-1 and sVCAM-1 decreased among participants assigned to intensive therapy, whereas they did not change among those in the conventional treatment group (P=0.03 for sICAM-1; P=0.03 for sVCAM-1). After adjustment for baseline levels and other factors, intensive therapy remained associated with a significant decrease in sICAM-1 (P=0.02) and an increase in sTNF-R1 (P=0.03). For hsCRP, there was a significant interaction between the top third of weight gain and treatment assignment (P=0.03). In subgroup analyses among subjects undergoing intensive therapy, hsCRP levels increased among those who gained the most weight, whereas it decreased among those in the bottom third of weight gain (P=0.0004). Intensive therapy in patients with type 1 diabetes mellitus reduced levels of sICAM-1 and increased levels of sTNF-R1 and of hsCRP among those who gained weight. These data demonstrate that the effect of intensive therapy on inflammation is complex and, to the extent that hsCRP is a risk factor, suggest that the risk of atherosclerosis among diabetic patients may be influenced by the degree of weight gain while undergoing intensive therapy.

Relation between markers of systemic vascular inflammation and smoking in women

Relation between markers of systemic vascular inflammation and smoking in women

C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.

Since inflammation is believed to have a role in the pathogenesis of cardiovascular events, measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events. We conducted a prospective, nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation. The markers included high-sensitivity C-reactive protein (hs-CRP), serum amyloid A, interleukin-6, and soluble intercellular adhesion molecule type 1 (sICAM-1). We also studied homocysteine and a variety of lipid and lipoprotein measurements. Cardiovascular events were defined as death from coronary heart disease, nonfatal myocardial infarction or stroke, or the need for coronary-revascularization procedures. Of the 12 markers measured, hs-CRP was the strongest univariate predictor of the risk of cardiovascular events; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 (95 percent confidence interval, 2.2 to 8.9). Other markers significantly associated with the risk of cardiovascular events were serum amyloid A (relative risk for the highest as compared with the lowest quartile, 3.0), sICAM-1 (2.6), interleukin-6 (2.2), homocysteine (2.0), total cholesterol (2.4), LDL cholesterol (2.4), apolipoprotein B-100 (3.4), HDL cholesterol (0.3), and the ratio of total cholesterol to HDL cholesterol (3.4). Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone (P<0.001). The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter (3.4 mmol per liter), the target for primary prevention established by the National Cholesterol Education Program. In multivariate analyses, the only plasma markers that independently predicted risk were hs-CRP (relative risk for the highest as compared with the lowest quartile, 1.5; 95 percent confidence interval, 1.1 to 2.1) and the ratio of total cholesterol to HDL cholesterol (relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.9). The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events.