Predictors of lack of glycemic control in persons with type 2 diabetes.

Background: Professional guidelines recommend an HbA1c < 7% for most people with diabetes and < 8.5% for those with relaxed glycemic goals. However, many people with type 2 diabetes mellitus (T2DM) are unable to achieve the desired HbA1c goal.

Plasma arginine levels in arginase deficiency in the "real world".

Background: Deficiency of arginase-1, the final enzyme in the urea cycle, causes a distinct clinical syndrome and is characterized biochemically by a high level of plasma arginine. While conventional therapy for urea cycle disorders can lower these levels to some extent, it does not normalize them. Until now, research on plasma arginine levels in this disorder has primarily relied on data from specialized tertiary centers, which limits the ability to assess the natural history and treatment efficacy of arginase-1 deficiency due to the small number of patients in each center and technical variations in plasma arginine measurements among different laboratories.

Insulin resistance probability score and incident cardiovascular disease.

Background: Insulin resistance (IR) is associated with cardiovascular disease (CVD). However, insulin immunoassay variability and scarce research of the elderly have hindered the adoption of IR assessment for CVD prevention. We asked whether the probability of having IR [p(IR)]-derived from insulin and C-peptide mass-spectrometry assays-was associated with CVD in the elderly.

Concordance of Cardiovascular Risk Factors and Behaviors in a Multiethnic US Nationwide Cohort of Married Couples and Domestic Partners.

Importance: Married couples and domestic partners have been reported to share similar environmental exposures, adopt similar behavior patterns, and have similar transferable characteristics. However, the degree to which couples share similar levels of cardiovascular risk factors and behaviors is uncertain.

Objective: To assess within-couple concordance of the American Heart Association-defined Life's Simple 7 (LS7).

Gaps in Dyslipidemia Care Among Working-Aged Individuals With Employer-Sponsored Health Care.

Background The American Heart Association and American College of Cardiology guidelines defined patient-management groups that would benefit from lowering of low-density lipoprotein cholesterol (LDL-C). We assessed gaps in dyslipidemia care among employees and spouses with health benefits. Methods and Results We studied 17 889 employees and spouses who were covered by an employer-sponsored health plan and participated in an annual health assessment.

LDL subfractions are associated with incident cardiovascular disease in the Malmö Prevention Project Study.

Background And Aims: After assessing the risk for cardiovascular disease (CVD) based on traditional risk factors, decisions concerning lipid lowering therapy might remain uncertain. To investigate whether lipoprotein subfraction levels could aid these decisions, we assessed the association between lipoprotein subfractions and CVD, after adjustment for traditional risk factors including standard lipids.

Methods: Using a case-cohort design, participants were randomly drawn from the Malmö Prevention Project (MPP), a population-based prospective study of 18,240 participants, and supplemented with additional incident CVD events (5764 participants, 1784 CVD events).

Use of low density lipoprotein particle number levels as an aid in statin treatment decisions for intermediate risk patients: a cost-effectiveness analysis.

Background: The 2013 ACC/AHA guideline recommended either no statin therapy or moderate-intensity statin therapy (MST) for intermediate risk patients-those with 5-7.5% 10-year risk and without cardiovascular disease (CVD), hypercholesterolemia or diabetes. The guideline further suggested that the therapy choice be based on patient-clinician discussions of risks and benefits.

Genetic risk for atrial fibrillation could motivate patient adherence to warfarin therapy: a cost effectiveness analysis.

Background: Atrial fibrillation (AF) increases risk of stroke, and although this stroke risk can be ameliorated by warfarin therapy, some patients decline to adhere to warfarin therapy. A prospective clinical study could be conducted to determine whether knowledge of genetic risk for AF could increase adherence to warfarin therapy for patients who initially declined therapy. As a prelude to a potential prospective clinical study, we investigated whether the use of genetic information to increase adherence could be cost effective.

Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history.

Aims: Genetic risk scores (GRSs) have been associated with coronary heart disease (CHD) in large studies. We asked whether expanding an established 27-variant GRS (GRS27) to a 50-variant GRS (GRS50) improved CHD prediction and whether GRSs are independent of self-reported family history of CHD.

Methods And Results: The association between GRSs and incident CHD was assessed in Cox models adjusting for established risk factors in 23 595 participants of the Malmö Diet and Cancer study--a prospective, population-based study.

A gene variant in CERS2 is associated with rate of increase in albuminuria in patients with diabetes from ONTARGET and TRANSCEND.

Although albuminuria and subsequent advanced stage chronic kidney disease are common among patients with diabetes, the rate of increase in albuminuria varies among patients. Since genetic variants associated with estimated glomerular filtration rate (eGFR) were identified in cross sectional studies, we asked whether these variants were also associated with rate of increase in albuminuria among patients with diabetes from ONTARGET and TRANSCEND-randomized controlled trials of ramipril, telmisartan, both, or placebo. For 16 genetic variants associated with eGFR at a genome-wide level, we evaluated the association with annual rate of increase in albuminuria estimated from urine albumin:creatinine ratio (uACR).

Twelve-single nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke.

Background And Purpose: Atrial fibrillation (AF) is prevalent and there is a clinical need for biomarkers to identify individuals at higher risk for AF. Fixed throughout a life course and assayable early in life, genetic biomarkers may meet this need. Here, we investigate whether multiple single nucleotide polymorphisms together as an AF genetic risk score (AF-GRS) can improve prediction of one's risk for AF.

Genome-wide study of gene variants associated with differential cardiovascular event reduction by pravastatin therapy.

Statin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin.

The contribution of a 9p21.3 variant, a KIF6 variant, and C-reactive protein to predicting risk of myocardial infarction in a prospective study.

Background: Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD) in prospective and case-control studies.

Single variants can explain the association between coronary heart disease and haplotypes in the apolipoprotein(a) locus.

Objective: LPA encodes apolipoprotein(a), and a CCTC haplotype in the LPA locus is associated with CHD. The 4399Met variant (rs3798220) of LPA has a risk estimate for CHD similar to that of the CCTC haplotype. We asked whether co-incidence with the 4399Met variant explained the association of the haplotype with CHD.

Effect of pravastatin therapy on coronary events in carriers of the KIF6 719Arg allele from the cholesterol and recurrent events trial.

A previous genetic analysis of the Cholesterol and Recurrent Events (CARE) trial found that carriers of the 719Arg allele of the kinesin family member 6 gene (KIF6) (rs20455), but not noncarriers, received significant event reduction from pravastatin therapy. However, that previous analysis of CARE included only Caucasian patients and was limited to the myocardial infarction components of the primary end point. Therefore, the aim of this study was to investigate whether pravastatin therapy reduced primary end point events in KIF6 719Arg carriers and noncarriers, separately, in the combined ethnic groups of CARE.

GOSR2 Lys67Arg is associated with hypertension in whites.

Background: Hypertension is a risk factor for coronary heart disease (CHD), but the causes of hypertension remain largely unknown. Genetic variation is thought to contribute to the etiology of hypertension. We tested a single-nucleotide polymorphism (SNP) (Lys67Arg, rs197922) in the Golgi SNAP Receptor Complex Member 2 (GOSR2) gene for association with hypertension and blood pressure (BP).

Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy.

Objective: A minor allele variant (rs3798220) of apolipoprotein(a) has been reported to be associated with elevated plasma lipoprotein(a) [Lp(a)] and increased cardiovascular risk. We investigated whether this allele was associated with elevated Lp(a) and cardiovascular risk in the Women's Health Study, a randomized trial of low-dose aspirin, and whether aspirin reduced cardiovascular risk in minor allele carriers.

Methods And Results: Genotypes of rs3798220 were determined for 25,131 initially healthy Caucasian participants.

Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction.

Myocardial infarction (MI) is a common complex disease with a genetic component. While several single nucleotide polymorphisms (SNPs) have been reported to be associated with risk of MI, they do not fully explain the observed genetic component of MI. We have been investigating the association between MI and SNPs that are located in genes and have the potential to affect gene function or expression.

A kinesin family member 6 variant is associated with coronary heart disease in the Women's Health Study.

Objectives: We asked if carriers of the 719Arg allele of kinesin family member 6 (KIF6) have increased risk of coronary heart disease (CHD) in a cohort of initially healthy Caucasian American women.

Background: The 719Arg allele of KIF6 (rs20455) has been reported to be associated with increased risk of CHD in a large population-based prospective study, ARIC (Atherosclerosis Risk in Communities), and in the placebo arms of 2 statin trials, CARE (Cholesterol and Recurrent Events) and WOSCOPS (West of Scotland Coronary Prevention Study). However, this KIF6 variant was not specifically investigated in the female subgroup in the ARIC study, and the CARE and WOSCOPS trials included only a small number of female patients.

Association of gene variants with incident myocardial infarction in the Cardiovascular Health Study.

Objective: We asked whether single nucleotide polymorphisms (SNPs) that had been nominally associated with cardiovascular disease in antecedent studies were also associated with cardiovascular disease in a population-based prospective study of 4522 individuals aged 65 or older.

Methods And Results: Based on antecedent studies, we prespecified a risk allele and an inheritance model for each of 74 SNPs. We then tested the association of these SNPs with myocardial infarction (MI) in the Cardiovascular Health Study (CHS).

Asp92Asn polymorphism in the myeloid IgA Fc receptor is associated with myocardial infarction in two disparate populations: CARE and WOSCOPS.

Objective: Statins reduce inflammation and risk of myocardial infarction (MI). Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we hypothesized that the FCAR Asp92Asn polymorphism is associated with risk of MI and that this risk would be modified by pravastatin.

Methods And Results: In the placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.

Gene variants of VAMP8 and HNRPUL1 are associated with early-onset myocardial infarction.

Objective: Identify gene variants associated with early-onset myocardial infarction (MI).

Methods And Results: We tested 11 647 single-nucleotide polymorphisms (SNPs) for association with early-onset MI in a case-control study (study 1 200 cases, 262 controls). To reduce the number of false positives among the 666 SNPs that were nominally associated with early-onset MI (P<0.