Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial.

Background: Elevated levels of high-sensitivity C-reactive protein (hsCRP) are associated with higher risk of adverse outcomes in patients at risk for or with established coronary artery disease. Retrospective analyses suggest that this risk may be modified with statin therapy. However, a role for hsCRP in monitoring the success of therapy remains uncertain.

Common variants of the endothelial nitric oxide synthase gene and the risk of coronary heart disease among U.S. diabetic men.

Endothelial nitric oxide synthase (eNOS) gene represents a promising candidate gene for coronary heart disease (CHD) because of its impact on eNOS activity. We systematically examined the associations of eight variants of the eNOS gene (two potentially functional variants [-786T>C and Glu298Asp] and six tagging single nucleotide polymorphisms) with CHD risk in a large cohort of diabetic patients. Among 861 diabetic men (>97% Caucasian) from the Health Professionals Follow-Up Study, 220 developed CHD, and 641 men without cardiovascular disease were used as control subjects.

Associations of the apolipoprotein A1/C3/A4/A5 gene cluster with triglyceride and HDL cholesterol levels in women with type 2 diabetes.

The apolipoprotein gene cluster (APOA1/C3/A4/A5) was recently associated with triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) in non-diabetic population. Little is known whether the variations in these genes affect lipid homeostasis in patients with type 2 diabetes. We examined the associations of 10 polymorphisms at APOA1/C3/A4/A5 gene cluster with blood lipids among 902 diabetic women.

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.

Inflammation and changes in metabolic syndrome abnormalities in US adolescents: findings from the 1988-1994 and 1999-2000 National Health and Nutrition Examination Surveys.

Background: Understanding of C-reactive protein (CRP) in adult metabolic syndrome is increasing; however, this relationship in children is less clear.

Methods: We compared the prevalence of metabolic abnormalities and metabolic syndrome in fasting 12- to 19-year-olds from the 1999-2000 and 1988-1994 National Health and Nutrition Examination Survey (NHANES). In the more recent dataset we explored the relationship between metabolic abnormalities and CRP as measured by a high-sensitivity assay.

C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, and the risk of distal colorectal adenoma in women.

Background: Determinants of insulin secretion and insulin-like growth factors (IGF) have been directly associated with risk for colorectal cancer. However, few studies have evaluated whether these factors are also associated with risk of colorectal adenoma, the main precursor lesion to colorectal cancer.

Methods: We identified 380 distal colorectal adenoma cases diagnosed between 1989 and 1998 and 380 controls among nondiabetic women from the cohort of 32,826 women, nested in the Nurses' Health Study, who provided blood samples in 1989 to 1990.

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.

Cross-sectional relations of serum aldosterone and urine sodium excretion to urinary albumin excretion in a community-based sample.

Experimental models suggest that increased aldosterone and sodium intake are associated with renovascular damage and resultant proteinuria. We hypothesized that serum aldosterone and urinary sodium would be associated with urinary albumin excretion, an indicator of kidney damage. We evaluated 2700 participants (53% women, mean age 58 years) from the Framingham Offspring Study who attended a routine examination between 1995 and 1998, who were free of heart failure and renal failure, and underwent testing for serum aldosterone, spot urinary sodium, and urinary albumin excretion (urine albumin/creatinine ratio, UACR), the latter two indexed to urinary creatinine.

Frequency of clinically unsuspected myocardial injury at a children's hospital.

Background: Ill children are at risk but rarely screened for myocardial injury. The frequency of such injury in ill children is unknown. Elevated levels of plasma cardiac troponin I (cTnI) can detect subclinical myocardial injury.

Mechanisms and biomarkers of cardiovascular injury induced by phosphodiesterase inhibitor III SK&F 95654 in the spontaneously hypertensive rat.

The cardiovascular injury of the type III selective PDE inhibitor SK&F 95654 was investigated in SHR. Twenty-four hours after a single sc injection of 100 or 200 mg/kg of the drug, rats exhibited cardiomyocyte necrosis and apoptosis, interstitial inflammation, hemorrhage and edema, as well as mesenteric arterial hemorrhage and necrosis, periarteritis, EC and VSMC apoptosis, EC activation, and MC activation and degranulation. Elevated serum levels of cTnT and decreased cTnT immunoperoxidase staining on cardiomyocytes were detected in the drug-treated rats.

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.

Increased inflammatory markers in children with familial hypercholesterolaemia.

Background: While data are abundant on increased levels of inflammatory markers in adult patients with hypercholesterolaemia, such data in children are limited. Therefore, we sought to investigate the degree and character of inflammation in children with heterozygous familial hypercholesterolaemia (FH) by measuring levels of neopterin, high-sensitivity C-reactive protein (hsCRP), and soluble CD40 ligand (sCD40L).

Materials And Methods: In the present study, we compared the concentration of inflammatory markers in children suffering from heterozygous FH (n = 207) with those in unaffected siblings (n = 84).

The association of serum lipids and inflammatory biomarkers with renal function in men with type II diabetes mellitus.

Dyslipidemia and inflammation may promote renal disease via mechanisms of vascular endothelial cell dysfunction in type II diabetes mellitus (DM). Sparse data, however, are available on the relation of lipids and inflammatory biomarkers and glomerular filtration rate (GFR) in type II DM. We performed a cross-sectional study of 732 men with type II DM enrolled in the Health Professionals' Follow-Up Study.

Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men.

Background: Apolipoprotein B (apoB) plasma levels reflect the concentration of proatherogenic lipoproteins very low-density lipoprotein and low-density lipoprotein (LDL), whereas non-high-density lipoprotein cholesterol (non-HDL-C) levels reflect the concentration of cholesterol transported by these particles.

Methods And Results: The aim of our study was to compare apoB, non-HDL-C, LDL cholesterol (LDL-C), and other lipid markers as predictors of coronary heart disease (CHD) in a nested case-control study among 18 225 participants in the Health Professionals Follow-up Study. Among men who were free of diagnosed cardiovascular disease at the time of blood collection, 266 had nonfatal myocardial infarction or fatal CHD during 6 years of follow-up.

HFE genetic variability, body iron stores, and the risk of type 2 diabetes in U.S. women.

To determine whether the HFE gene variants H63D and C282Y are associated with body iron stores and the risk of type 2 diabetes, we conducted a nested case-control study of 714 incident cases of type 2 diabetes and 1,120 matching control subjects in a prospective cohort, the Nurses' Health Study. In both healthy control and diabetic case subjects, H63D homozygosity, C282Y, and the compound heterozygotes were associated with significantly higher levels of plasma ferritin and significantly lower ratios of transferrin receptors to ferritin. Such effects were independent of age, BMI, and lifestyle factors.

Mediating effects of inflammatory biomarkers on insulin resistance associated with obesity.

Objective: Obesity is associated with elevated levels of biomarkers of inflammation and endothelial dysfunction [including C-reactive protein (CRP), E-selectin, and intercellular adhesion molecule-1], as well as insulin resistance (IR) and type 2 diabetes. We tested the hypothesis that these biomarkers mediate associations among obesity, IR, and risk of diabetes.

Research Methods And Procedures: We stratified 510 initially non-diabetic women in the Nurses' Health Study cohort into four phenotypes above/below median BMI (27 kg/m2) and waist circumference (81 cm): low BMI-low waist (LBLW; N = 190), low BMI-high waist (LBHW; N = 74), high BMI-low waist (HBLW; N = 27), and high BMI-high waist (HBHW; N = 219).

Relationship between uncontrolled risk factors and C-reactive protein levels in patients receiving standard or intensive statin therapy for acute coronary syndromes in the PROVE IT-TIMI 22 trial.

Objectives: This study sought to evaluate what set of factors correlate with higher or lower C-reactive protein (CRP) levels in patients receiving standard and intensive statin therapy.

Background: C-reactive protein levels in blood are becoming recognized as a potential means of monitoring cardiovascular risk. Although statin therapy is known to reduce CRP levels, many patients have a high CRP level despite statin therapy.

D-dimer and inflammatory markers as predictors of functional decline in men and women with and without peripheral arterial disease.

Objectives: To determine whether higher circulating levels of inflammatory and thrombotic markers are associated with greater decline in lower extremity performance.

Design: Prospective cohort.

Setting: Academic medical center.

Tandem mass spectrometry method for the quantification of serum busulfan.

Busulfan, an alkylating agent, is most commonly used as a component of bone marrow transplantation preoperative regimens. Significant interpatient and intrapatient variations in pharmacokinetics require individualizing the dosage based on area under the time-versus-concentration curve. Timely result reporting is critical to dose adjustment to reduce morbidity and mortality associated with the regimen.

Hyperproinsulinaemia and risk of Type 2 diabetes mellitus in women.

Aims: Our objective was to examine prospectively the associations between fasting plasma proinsulin and the proinsulin/insulin ratio and the incidence of Type 2 diabetes in women.

Subjects And Methods: We designed a nested case-control study within the Nurses' Health Study, a cohort of 121,700 US women aged 30-55 years at study inception in 1976. Fasting plasma proinsulin, specific insulin and C-peptide levels were determined in 183 women with a new diagnosis of diabetes made after blood sampling between 1989 and 1990, and 369 control subjects without diabetes.

Moderate alcohol consumption and lower levels of inflammatory markers in US men and women.

Objective: Moderate alcohol consumption is associated with substantially lower risk of cardiovascular disease (CVD). We assessed the relationship between alcohol intake and inflammatory markers to partially explain this beneficial effect.

Methods And Results: From two large prospective studies, we sampled 959 healthy male and 473 healthy female health professionals with reported alcohol intake.

Alcohol consumption and high-density lipoprotein levels: the effect of ADH1C genotype, gender and menopausal status.

We previously demonstrated that a functional polymorphism in alcohol dehydrogenase type 1C (ADH1C, also known as ADH3) modifies the association between moderate alcohol consumption and high-density lipoprotein (HDL) levels and risk of myocardial infarction among older men. In this study, we investigated the effect of the ADH1C gamma(1) and gamma(2) alleles on the relationship between alcohol consumption and HDL levels among four populations with varied exposure to endogenous and exogenous estrogens: premenopausal women, middle-to-older aged men, postmenopausal women currently using postmenopausal hormones (PMH) and postmenopausal women not currently using PMH. We observed an interaction between moderate alcohol consumption and ADH1C genotype on HDL level that was similar among middle-to-older aged men and postmenopausal women not using PMH.