Lack of Association Between Genetic Variation in 9 Innate Immunity Genes and Baseline CRP Levels.

It is well-known that baseline levels of C-reactive protein (CRP) are an independent cardiovascular risk factor. We hypothesized that genetic variation with significant influence on CRP levels might be found in genes of the innate immunity system. We performed a candidate gene association study examining common single nucleotide polymorphisms in 9 innate immunity genes (CARD15, IRAK1, IRAK4, LBP, LY86, MEFV, TLR2, TLR4 and NFKB1) in relation to CRP levels.

Lack of association between genetic variation in 9 innate immunity genes and baseline CRP levels.

It is well-known that baseline levels of C-reactive protein (CRP) are an independent cardiovascular risk factor. We hypothesized that genetic variation with significant influence on CRP levels might be found in genes of the innate immunity system. We performed a candidate gene association study examining common single nucleotide polymorphisms in 9 innate immunity genes (CARD15, IRAK1, IRAK4, LBP, LY86, MEFV, TLR2, TLR4 and NFKB1) in relation to CRP levels.

Additive value of immunoassay-measured fibrinogen and high-sensitivity C-reactive protein levels for predicting incident cardiovascular events.

Background: Current guidelines suggest measuring high-sensitivity C-reactive protein (hs-CRP) as an aid to coronary risk assessment in adults without cardiovascular disease (CVD). Whether other inflammatory biomarkers, such as fibrinogen, add further prognostic information is uncertain.

Methods And Results: In a prospective study of 27,742 initially healthy middle-aged women, the associations of baseline immunoassay fibrinogen and hs-CRP measurements with incident CVD were examined over a 10-year follow-up period.

Polymorphisms of the phosphodiesterase 4D, cAMP-specific (PDE4D) gene and risk of ischemic stroke: a prospective, nested case-control evaluation.

Background And Purpose: In an Icelandic population, gene variants of the phosphodiesterase 4D, cAMP-specific (PDE4D) gene were reported to be risk predictors for ischemic stroke. Case-control studies in other populations have yielded mixed evidence for association. A recent analysis in a prospective, non-Icelandic study found an association with stroke after stratification by hypertension.

The effect of including C-reactive protein in cardiovascular risk prediction models for women.

Background: While high-sensitivity C-reactive protein (hsCRP) is an independent predictor of cardiovascular risk, global risk prediction models incorporating hsCRP have not been developed for clinical use.

Objective: To develop and compare global cardiovascular risk prediction models with and without hsCRP.

Design: Observational cohort study.

Cholesterol, C-reactive protein, and cerebrovascular events following intensive and moderate statin therapy.

Background: While statins have been shown to reduce cerebrovascular events (CVE), the relationship between cholesterol, C-reactive protein (CRP), and CVE in patients treated with different statin strategies is still being explored.

Methods: PROVE IT-TIMI 22 was a randomized trial of intensive (atorvastatin 80 mg/day) and moderate (pravastatin 40 mg/day) statin therapy in 4,162 patients with acute coronary syndromes followed for an average of 24 months; serial biomarkers allowed for an assessment of the lipid and non-lipid effects of statins as they relate to CVE.

Results: In this study, 45 patients on intensive statin therapy and 40 patients on moderate statin therapy had a CVE during the study period (2.

Genetic variants of arachidonate 5-lipoxygenase-activating protein, and risk of incident myocardial infarction and ischemic stroke: a nested case-control approach.

Background And Purpose: Recent findings have implicated specific gene polymorphisms of arachidonate 5-lipoxygenase-activating protein (ALOX5AP), and 2 at-risk haplotypes (HapA, HapB) in myocardial infarction and stroke. To date, no prospective data are available.

Methods: We evaluated 10 specific Icelandic ALOX5AP gene variants among 600 male participants with incident atherothrombotic events (myocardial infarction [MI] or ischemic stroke) and among 600 age- and smoking-matched male participants, all white, who remained free of reported cardiovascular disease during follow-up within the Physicians' Health Study cohort.

Risk factors for progression of peripheral arterial disease in large and small vessels.

Background: Data on the natural history of peripheral arterial disease (PAD) are scarce and are focused primarily on clinical symptoms. Using noninvasive tests, we assessed the role of traditional and novel risk factors on PAD progression. We hypothesized that the risk factors for large-vessel PAD (LV-PAD) progression might differ from small-vessel PAD (SV-PAD).

Polymorphisms in the advanced glycosylation end product-specific receptor gene and risk of incident myocardial infarction or ischemic stroke.

Background And Purpose: Recent findings of an association between polymorphisms of advanced glycosylation end product-specific receptor (AGER) and risk of diabetic vasculopathy have generated great interest. However, to date, no genetic-epidemiological data are available on risk of atherothrombotic events among nondiabetic populations.

Methods: Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated 3 AGER genetic variants: -429T>C, -374T>A, and Gly82Ser, among 600 white individuals who subsequently developed atherothrombotic event (incident myocardial infarction or ischemic stroke) and among 600 age- and smoking-matched white individuals who remained free of reported vascular disease during follow-up (controls).

A prospective assessment of the Y402H variant in complement factor H, genetic variants in C-reactive protein, and risk of age-related macular degeneration.

Purpose: Two biologically related factors, complement factor H (CFH) and C-reactive protein (CRP), have been associated with AMD. The Y402H variant of CFH is located within the binding site of CFH for CRP. Although plasma CRP levels have been related to AMD and plasma CRP levels are partly determined by genetic variation, there is no information on whether genetic variants in CRP are associated with AMD.

Valsartan, blood pressure reduction, and C-reactive protein: primary report of the Val-MARC trial.

Increased levels of high-sensitivity C-reactive protein (hsCRP) are associated with incident hypertension as well as cardiovascular events, and angiotensin II is a potent proinflammatory mediator. However, whether angiotensin receptor blockade lowers hsCRP is uncertain. We performed a randomized trial in which 1668 patients with stage 2 hypertension were treated with 160 mg valsartan or 160/12.

Reported outcomes in major cardiovascular clinical trials funded by for-profit and not-for-profit organizations: 2000-2005.

Context: In surveys based on data available prior to 2000, clinical trials funded by for-profit organizations appeared more likely to report positive findings than those funded by not-for-profit organizations. Whether this situation has changed over the past 5 years or whether similar effects are present among jointly funded trials is unknown.

Objective: To determine in contemporary randomized cardiovascular trials the association between funding source and the likelihood of reporting positive findings.

Platelet expression profiling and clinical validation of myeloid-related protein-14 as a novel determinant of cardiovascular events.

Background: Platelets participate in events that immediately precede acute myocardial infarction. Because platelets lack nuclear DNA but retain megakaryocyte-derived mRNAs, the platelet transcriptome provides a novel window on gene expression preceding acute coronary events.

Methods And Results: We profiled platelet mRNA from patients with acute ST-segment-elevation myocardial infarction (STEMI, n=16) or stable coronary artery disease (n=44).

Oxidized low-density lipoprotein in children with familial hypercholesterolemia and unaffected siblings: effect of pravastatin.

Objectives: To assess the role of oxidized phospholipids (OxPLs) in children with familial hypercholesterolemia (FH) and the effect of pravastatin.

Background: Oxidized phospholipids are a major component of oxidized low-density lipoprotein (OxLDL) and are bound to lipoprotein (a) [Lp(a)]. The significance of OxPL markers in children is unknown.

Polymorphism in the beta2-adrenergic receptor and lipoprotein lipase genes as risk determinants for idiopathic venous thromboembolism: a multilocus, population-based, prospective genetic analysis.

Background: Candidate genes in inflammation, thrombosis, coagulation, and lipid metabolism pathways have been implicated in venous thromboembolism (VTE).

Methods And Results: Using DNA samples collected at baseline in the Physicians' Health Study cohort, we genotyped 92 polymorphisms from 56 candidate genes among 304 individuals who subsequently developed VTE (144 idiopathic, 156 secondary cases) and among 2070 individuals who remained free of reported vascular disease over a mean follow-up of 13.2 years to prospectively determine whether these gene polymorphisms contribute to the risk of VTE.

C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients.

Several emerging plasma biomarkers may ultimately prove useful in risk stratification and prognosis of cardiovascular disease. The clinical utility of these biomarkers will depend on their ability to provide a reflection of the underlying atherosclerotic burden or activity; the ability to provide reliable, accurate, and cost-effective information; and the ability to predict future events. High-sensitivity C-reactive protein (hs-CRP) fulfills many, if not all, of these criteria, and blood levels of hs-CRP are now commonly used in clinical practice to improve vascular risk prediction in primary and secondary prevention across all levels of low-density lipoprotein-cholesterol (LDL-C), all levels of the Framingham Risk Score, and all levels of metabolic syndrome.

Functional decline in patients with and without peripheral arterial disease: predictive value of annual changes in levels of C-reactive protein and D-dimer.

Background: Inflammation may be a potential mechanism of aging-related functional decline. We determined whether greater annual increases in levels of high sensitivity C-reactive protein (hsCRP) and D-dimer predicted greater decline in functioning among persons with and without lower extremity peripheral arterial disease (PAD).

Methods: We prospectively studied 296 men and women with PAD and 191 without PAD.

Association of physical activity and body mass index with novel and traditional cardiovascular biomarkers in women.

Context: There are few data directly comparing the effects of physical activity and body weight on cardiovascular biomarkers.

Objective: To examine the association of physical activity and body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) alone and in combination with cardiovascular biomarkers.

Design, Setting, And Participants: Cross-sectional analysis of 27,158 apparently healthy US women (mean age, 54.

A prospective study of hemoglobin A1c concentrations and risk of breast cancer in women.

Impaired glucose metabolism and hyperinsulinemia have been hypothesized to increase breast cancer risk. However, findings from observational studies relating blood concentrations of hyperinsulinemia markers to breast cancer risk have been inconsistent. We prospectively evaluated whether hemoglobin A1c (HbA1c) concentrations predict breast cancer risk in a large female cohort.

High-sensitivity C-reactive protein and cognitive function in older women.

Background: Inflammatory processes may be involved in the development of dementia, although findings from epidemiologic studies directly examining inflammatory markers and dementia or its precursor, impaired cognitive function, are inconsistent.

Methods: We measured plasma levels of the inflammatory marker, C-reactive protein, using a high-sensitivity assay (hs-CRP) in 4,231 older participants of the Women's Health Study, who provided blood samples between 1992 and 1996 when they were age 60 to 90 years. From 1998 to 2000, we administered a battery of 5 cognitive tests measuring general cognition, verbal memory, and category fluency.