Association Between Homocysteine and Vascular Calcification Incidence, Prevalence, and Progression in the MESA Cohort.

Background While elevated homocysteine has been associated with calcification in several studies, its importance as a cardiovascular risk factor remains unclear. This study examines the relationship between homocysteine and vascular and valve calcification in the MESA (Multi-ethnic Study of Atherosclerosis) cohort. Methods and Results MESA participants with baseline homocysteine measurements and cardiac computed tomography scans were included (N=6789). Baseline and follow-up assessment of vascular (coronary artery [CAC], descending thoracic aorta [DTAC]) and valve (aortic valve [AVC], mitral annular [MAC]) calcification was performed. Prevalence ratio/relative risk regression was used to assess the relationship of homocysteine with prevalent and incident calcification, and multivariable logistic regression was used to assess associations between homocysteine and calcification progression. Elevated homocysteine was associated with greater relative risk of prevalent and incident CAC and incident DTAC. We also identified a strong association between elevated homocysteine and CAC and DTAC progression. Elevated homocysteine was found to confer a >2-fold increased risk of severe CAC progression (defined as ΔCAC ≥100/year) and an ≈1.5-fold increased risk for severe DTAC progression (defined as ΔDTAC ≥100/year). Conclusions To our knowledge, this is the first study demonstrating an association between elevated homocysteine and both incidence and progression of coronary and extra-coronary vascular calcification. Our findings suggest a potential role for elevated homocysteine as a risk factor for severe vascular calcification progression. Future studies are warranted to further assess the utility of homocysteine as a biomarker for vascular calcification incidence and progression. Clinical Trial Registration https://www.clinicaltrials.gov/. Unique identifier: NCT00005487

Association between adiponectin and heart failure risk in the Physicians' Health Study

Limited data are available on the association between adiponectin and incident heart failure. In the current ancillary study to the Physicians' Health Study, we used a prospective nested-case control design to examine whether plasma adiponectin concentration was related to the risk of heart failure. We selected 787 incident heart failure cases and 787 matched controls for the current analysis. Each control was selected using a risk set sampling technique at the time of the occurrence of the index case and matched on year of birth, age at blood collection, and race. Adiponectin was measured using ELISA. Heart failure occurrence was self-reported in annual follow-up questionnaire. Validation of self-reported heart failure in this cohort has been published. The mean age was 58.7 years. In a conditional logistic regression adjusting for age, race, time of blood collection, year of birth, hypertension, atrial fibrillation, smoking, alcohol intake, and exercise, estimates of the relative risk (95% confidence interval) were 1.0 (ref), 0.74 (0.53–1.04), 0.67 (0.48–0.94), 0.70 (0.50–0.99), and 0.92 (0.65–1.30) from the lowest to the highest quintile of adiponectin, respectively, p for quadratic trend 0.004. Additional adjustment for potential mediating factors including diabetes, C-reactive protein, and body mass index led to the attenuation of the estimate of effect [1.0 (ref), 0.81 (0.57–1.15), 0.75 (0.53–1.06), 0.83 (0.58–1.18), and 1.26 (0.87–1.81) across consecutive quintiles of adiponectin]. Our data are consistent with a J-shaped association between total adiponectin and the risk of heart failure among US male physicians

Vitamin D Status during Pregnancy and the Risk of Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort

Aims Emerging evidence suggests that maternal vitamin D status may be associated with gestational diabetes (GDM). However, the temporal relation remains unclear due to the lack of longitudinal data on vitamin D over pregnancy. We aimed to prospectively and longitudinally investigate vitamin D status during early to mid‐pregnancy in relation to GDM risk. Methods In a nested case‐control study of 107 GDM cases and 214 controls within the Fetal Growth Studies‐Singleton Cohort, plasma levels of 25‐hydroxyvitamin D2 and D3 (25(OH)D) and vitamin D binding protein were measured at gestational weeks 10‐14, 15‐26, 23‐31, and 33‐39; we further calculated total, free, and bioavailable 25(OH)D. Conditional logistic regression models and linear mixed‐effects models were used. Results We observed a threshold effect for the relation of vitamin D biomarkers with GDM risk. Vitamin D deficiency (<50 nmol/L) at 10‐14 gestational weeks was associated with a 2.82‐fold increased risk for GDM [odds ratio (OR) =2.82, 95% confidence interval (CI): 1.15‐6.93]. Women with persistent vitamin D deficiency at 10‐14 and 15‐26 weeks of gestation had a 4.46‐fold elevated risk for GDM compared to women persistently non‐deficient (OR=4.46, 95% CI: 1.15‐17.3). Conclusions Maternal vitamin D deficiency as early as the first trimester of pregnancy was associated with an elevated risk of GDM. The association was stronger for women who were persistently deficient through the 2nd trimester. Assessment of vitamin D status in early pregnancy may be clinically important and valuable for improving risk stratification and developing effective interventions for the primary prevention of GDM

Lipoprotein(a) and the pooled cohort equations for ASCVD risk prediction: The Multi-Ethnic Study of Atherosclerosifs

Background and aimsLipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) but is not included in the Pooled Cohort Equations (PCE). We aimed to assess how well the PCE predict 10-year event rates in individuals with elevated Lp(a), and whether the addition of Lp(a) improves risk prediction.MethodsWe compared observed versus PCE-predicted 10-year ASCVD event rates, stratified by Lp(a) level and ASCVD risk category using Poisson regression, and evaluated the association between Lp(a)&nbsp;&gt;&nbsp;50&nbsp;mg/dL and ASCVD risk using Cox proportional hazards models in the Multi-Ethnic Study of Atherosclerosis (MESA). We evaluated the C-index and net reclassification improvement (NRI) with addition of Lp(a) to the PCE.ResultsThe study population included 6639 individuals (20%, n&nbsp;=&nbsp;1325 with elevated Lp(a)). The PCE accurately predicted 10-year event rates for individuals with elevated Lp(a) with observed event rates falling within predicted limits. Elevated Lp(a) was associated with increased risk of CVD events overall (HR 1.27, 95% CI 1.00-1.60), particularly in low (HR 2.45, 95% CI 1.40-4.31), and high-risk (HR 1.41, 95% CI 1.02-1.96) individuals. Continuous NRI (95% CI) with the addition of Lp(a) to the PCE for CVD was 0.0963 (0.0158-0.1953) overall, and 0.2999 (0.0876, 0.5525) among low-risk individuals.ConclusionsThe PCE performs well for event rate prediction in individuals with elevated Lp(a). However, Lp(a) is associated with increased CVD risk, and the addition of Lp(a) to the PCE improves risk prediction, particularly among low-risk individuals. These results lend support for increasing use of Lp(a) testing for risk assessment

Circulating and Dietary Omega‐3 and Omega‐6 Polyunsaturated Fatty Acids and Incidence of CVD in the Multi‐Ethnic Study of Atherosclerosis

Background: Dietary guidelines support intake of polyunsaturated fatty acids (PUFAs) in fish and vegetable oils. However, some controversy remains about benefits of PUFAs, and most prior studies have relied on self‐reported dietary assessment in relatively homogeneous populations. Methods and Results: In a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans), plasma phospholipid PUFAs were measured at baseline (2000–2002) using gas chromatography and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease (CVD) events (including coronary heart disease and stroke; n=189) were prospectively identified through 2010 during 19 778 person‐years of follow‐up. In multivariable‐adjusted Cox models, circulating n‐3 eicosapentaenoic acid and docosahexaenoic acid were inversely associated with incident CVD, with extreme‐quartile hazard ratios (95% CIs) of 0.49 for eicosapentaenoic acid (0.30 to 0.79; Ptrend=0.01) and 0.39 for docosahexaenoic acid (0.22 to 0.67; Ptrend<0.001). n‐3 Docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race/ethnicities (P‐interaction=0.01). No significant associations with CVD were observed for circulating n‐3 alpha‐linolenic acid or n‐6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self‐reported dietary PUFA were consistent with those of the PUFA biomarkers. All associations were similar across racial‐ethnic groups, except those of docosapentaenoic acid. Conclusions: Both dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, but not alpha‐linolenic acid or n‐6 PUFA, were inversely associated with CVD incidence. These findings suggest that increased consumption of n‐3 PUFA from seafood may prevent CVD development in a multiethnic population

Patient Navigators Connecting Patients to Community Resources to Improve Diabetes Outcomes

BACKGROUND: Despite the recognized importance of lifestyle modification in reducing risk of developing type 2 diabetes and in diabetes management, the use of available community resources by both patients and their primary care providers (PCPs) remains low. The patient navigator model, widely used in cancer care, may have the potential to link PCPs and community resources for reduction of risk and control of type 2 diabetes. In this study we tested the feasibility and acceptability of telephone-based nonprofessional patient navigation to promote linkages between the PCP office and community programs for patients with or at risk for diabetes. METHODS: This was a mixed-methods interventional prospective cohort study conducted between November 2012 and August 2013. We included adult patients with and at risk for type 2 diabetes from six primary care practices. Patient-level measures of glycemic control, diabetes care, and self-efficacy from medical records, and qualitative interview data on acceptability and feasibility, were used. RESULTS: A total of 179 patients participated in the study. Two patient navigators provided services over the phone, using motivational interviewing techniques. Patient navigators provided regular feedback to PCPs and followed up with the patients through phone calls. The patient navigators made 1028 calls, with an average of 6 calls per patient. At follow-up, reduction in HbA1c (7.8 ± 1.9% vs 7.2 ± 1.3%; P = .001) and improvement in patient self-efficacy (3.1 ± 0.8 vs 3.6 ± 0.7; P < .001) were observed. Qualitative analysis revealed uniformly positive feedback from providers and patients. CONCLUSIONS: The patient navigator model is a promising and acceptable strategy to link patient, PCP, and community resources for promoting lifestyle modification in people living with or at risk for type 2 diabetes

Visualizing Exotic Orbital Texture in the Single-Layer Mott Insulator 1T-TaSe2

Mott insulating behavior is induced by strong electron correlation and can lead to exotic states of matter such as unconventional superconductivity and quantum spin liquids. Recent advances in van der Waals material synthesis enable the exploration of novel Mott systems in the two-dimensional limit. Here we report characterization of the local electronic properties of single- and few-layer 1T-TaSe2 via spatial- and momentum-resolved spectroscopy involving scanning tunneling microscopy and angle-resolved photoemission. Our combined experimental and theoretical study indicates that electron correlation induces a robust Mott insulator state in single-layer 1T-TaSe2 that is accompanied by novel orbital texture. Inclusion of interlayer coupling weakens the insulating phase in 1T-TaSe2, as seen by strong reduction of its energy gap and quenching of its correlation-driven orbital texture in bilayer and trilayer 1T-TaSe2. Our results establish single-layer 1T-TaSe2 as a useful new platform for investigating strong correlation physics in two dimensions

The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation.

Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation