Importance of the lipid-related pathways in the association between statins, mortality and cardiovascular disease risk : the multi-ethnic study of atherosclerosis

PURPOSE: Estimating how much of the impact of statins on coronary heart diseases (CHD), cardiovascular disease (CVD), and mortality risk is attributable to their effect on low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglycerides. METHODS: A semi-parametric g-formula estimator together with data from the Multi-Ethnic Study of Atherosclerosis (a prospective multi-center cohort study) was utilized to perform a mediation analysis. A total of 5280 participants, men and women of various race/ethnicities from multiple sites across the United States, were considered in the current study. RESULTS: The adherence adjusted total relative risk reduction (RRR) estimate (95% confidence interval) of statins on CHD was 14% (-16%, 37%), and the indirect component through LDL was 23% (-4%, 58%). For CVD, the total RRR was 23% (2%, 40%), and the indirect component through LDL was 5% (-13%, 25%). The total RRR of mortality was 18% (-1%, 35%), and the indirect component through LDL was -4% (-17%, 12%). The estimated indirect components through HDL and triglycerides were close to zero with narrow confidence intervals for all 3 outcomes. CONCLUSIONS: The estimated effect of statins on mortality, CVD, and CHD appeared to be independent of their estimated effect on HDL and triglycerides. Our study provides evidence that the preventive effect of statins on CHD could be attributed in large part to their effect on LDL. Our g-formula estimator is a promising approach to elucidate pathways, even if it is hard to make firm conclusions for the LDL pathway on mortality and CV

Perceived access and barriers to care among illicit drug users and hazardous drinkers: findings from the Seek, Test, Treat, and Retain data harmonization initiative (STTR).

BACKGROUND: Illicit drug use (DU) and hazardous drinking (HD) among marginalized populations may be associated with greater barriers to care. METHODS: We used baseline data on the participants of the Seek, Test, Treat, and Retain data harmonization initiative. DU includes use of any illicit drugs within the past 6 months. HD was defined as scores ≥8 for men and ≥ 7 for women on Alcohol Use Disorders Identification Test within the past 12 months. Social support scores were assigned by summing scores from individual questions related to social support. Two outcomes for multivariable regression models and mediation analysis were perceived access to care and perceived barriers to care scores, calculated from summated points from individual questions within each domain. All models were adjusted for age, gender, race/ethnicity, and social support and stratified by HIV status. RESULTS: Among 1403 illicit drug users and 4984 non-drug users, the mean age was 39.6 ± 12.2 years old, 71% were male, 57% African Americans, and 39% Hispanic/Latinos. Over 25% reported difficulties in covering medical costs and finding transportation to health care facilities and greater proportions of drug users and hazardous drinkers reported these issues than non-DU/non-HD. In multivariable models, DU and HD were both independently associated with having greater barriers to care (β: 0.49 (95% confidence interval: 0.19 to 0.79) p \u3c 0.01; 0.31 (0.18 to 0.45) \u3c 0.01) in HIV-negative participants. Neither DU nor HD was strongly associated with barriers to care for HIV-positive participants. Social support was associated with better perceived access to care and fewer barriers to care in the HIV-negative participants. CONCLUSION: The current study found that financial burdens of care, logistical difficulties in accessing care, and low social support were common challenges among individuals using illicit drugs and/or drinking hazardously. Addressing structural barriers and strengthening social support may be important strategies to improve health care among marginalized populations, regardless of HIV status

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

Myocardial infarction and stroke associated with diuretic based two drug antihypertensive regimens: population based case-control study

Objective To examine the association of myocardial infarction and stroke incidence with several commonly used two drug antihypertensive treatment regimens

Comparison of the clinical and economic outcomes between open and minimally invasive appendectomy and colectomy: evidence from a large commercial payer database

Background: Appendectomy and colectomy are commonly performed surgical procedures. Despite evidence demonstrating advantages with the minimally invasive surgical (MIS) approach, open procedures occur with greater prevalence. Therefore, there is still controversy as to whether the MIS approach is safer or more cost effective. Methods: A retrospective analysis was performed using a large commercial payer database. The data included information on 7,532 appendectomies and 2,745 colectomies. Data on the distribution of patient demographic and comorbidity characteristics associated with the MIS and open approaches were reviewed. The corresponding complication rates and expenditures were analyzed. Summary statistics were compared using chi-square tests, and generalized linear models were constructed to estimate expenditures while controlling for patient characteristics. Results: The patients undergoing MIS and open colectomy showed no significant variations in age distribution or marginal age differences for appendectomy. Significantly more patients experienced an infection postoperatively, and procedure-specific complications were more common in the open group for both procedures (P < 0.05). The postsurgical hospital stay was longer for the patients treated using the open techniques, differing an average of half a day for appendectomies and significantly more (4 days) for colectomy (P < 0.05). Readmission rates differed little between the two approaches. Procedures performed through an MIS approach were associated with lower expenditures than for the open technique, with differences ranging from $700 for appendectomy patients (P < 0.05) to$15,200 for colectomy patients (P < 0.05). Conclusions: Minimally invasive appendectomy and colectomy were associated with lower infection rates, fewer complications, shorter hospital stays, and lower expenditures than open surgery

Evaluation of respondent-driven sampling in seven studies of people who use drugs from rural populations: findings from the Rural Opioid Initiative

Background Accurate prevalence estimates of drug use and its harms are important to characterize burden and develop interventions to reduce negative health outcomes and disparities. Lack of a sampling frame for marginalized/stigmatized populations, including persons who use drugs (PWUD) in rural settings, makes this challenging. Respondent-driven sampling (RDS) is frequently used to recruit PWUD. However, the validity of RDS-generated population-level prevalence estimates relies on assumptions that should be evaluated. Methods RDS was used to recruit PWUD across seven Rural Opioid Initiative studies between 2018-2020. To evaluate RDS assumptions, we computed recruitment homophily and design effects, generated convergence and bottleneck plots, and tested for recruitment and degree differences. We compared sample proportions with three RDS-adjusted estimators (two variations of RDS-I and RDS-II) for five variables of interest (past 30-day use of heroin, fentanyl, and methamphetamine; past 6-month homelessness; and being positive for hepatitis C virus (HCV) antibody) using linear regression with robust confidence intervals. We compared regression estimates for the associations between HCV positive antibody status and (a) heroin use, (b) fentanyl use, and (c) age using RDS-1 and RDS-II probability weights and no weights using logistic and modified Poisson regression and random-effects meta-analyses. Results Among 2,842 PWUD, median age was 34 years and 43% were female. Most participants (54%) reported opioids as their drug of choice, however regional differences were present (e.g., methamphetamine range: 4-52%). Many recruitment chains were not long enough to achieve sample equilibrium. Recruitment homophily was present for some variables. Differences with respect to recruitment and degree varied across studies. Prevalence estimates varied only slightly with different RDS weighting approaches, most confidence intervals overlapped. Variations in measures of association varied little based on weighting approach. Conclusions RDS was a useful recruitment tool for PWUD in rural settings. However, several violations of key RDS assumptions were observed which slightly impacts estimation of proportion although not associations

Assessing and Refining Myocardial Infarction Risk Estimation Among Patients With Human Immunodeficiency Virus: A Study by the Centers for AIDS Research Network of Integrated Clinical Systems

Persons with human immunodeficiency virus (HIV) treated with antiretroviral therapy (ART) have improved longevity but are at elevated risk for myocardial infarction (MI) due to common MI risk factors and HIV-specific factors. Despite these elevated MI rates, optimal methods to predict MI risks for HIV-infected persons remain unclear

Selective Serotonin Reuptake Inhibitor Use Is Associated with Right Ventricular Structure and Function: The MESA-Right Ventricle Study

PURPOSE:Serotonin and the serotonin transporter have been implicated in the development of pulmonary hypertension (PH). Selective serotonin reuptake inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use on right ventricular (RV) structure and function are unknown. We hypothesized that SSRI use would be associated with RV morphology in a large cohort without cardiovascular disease (N = 4114). METHODS:SSRI use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were assessed via cardiac magnetic resonance imaging. The cross-sectional relationship between SSRI use and each RV measure was assessed using multivariable linear regression; analyses for RV mass and end-diastolic volume (RVEDV) were stratified by sex. RESULTS:After adjustment for multiple covariates including depression and left ventricular measures, SSRI use was associated with larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48-5.02 mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08 g, 95% CI 0.19-1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02-12.40 mL, p = 0.001). SSRI use may have been associated with larger RVEDV among women and larger RV end-systolic volume in both sexes. CONCLUSIONS:SSRI use was associated with higher RVSV in cardiovascular disease-free individuals and, among men, greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at risk for) RV dysfunction and the role of sex in modifying this relationship warrant further study

A gene-centric association scan for Coagulation Factor VII levels in European and African Americans: the Candidate Gene Association Resource (CARe) Consortium

Polymorphisms in several distinct genomic regions, including the F7 gene, were recently associated with factor VII (FVII) levels in European Americans (EAs). The genetic determinants of FVII in African Americans (AAs) are unknown. We used a 50 000 single nucleotide polymorphism (SNP) gene-centric array having dense coverage of over 2 000 candidate genes for cardiovascular disease (CVD) pathways in a community-based sample of 16 324 EA and 3898 AA participants from the Candidate Gene Association Resource (CARe) consortium. Our aim was the discovery of new genomic loci and more detailed characterization of existing loci associated with FVII levels. In EAs, we identified three new loci associated with FVII, of which APOA5 on chromosome 11q23 and HNF4A on chromosome 20q12–13 were replicated in a sample of 4289 participants from the Whitehall II study. We confirmed four previously reported FVII-associated loci (GCKR, MS4A6A, F7 and PROCR) in CARe EA samples. In AAs, the F7 and PROCR regions were significantly associated with FVII. Several of the FVII-associated regions are known to be associated with lipids and other cardiovascular-related traits. At the F7 locus, there was evidence of at least five independently associated SNPs in EAs and three independent signals in AAs. Though the variance in FVII explained by the existing loci is substantial (20% in EA and 10% in AA), larger sample sizes and investigation of lower frequency variants may be required to identify additional FVII-associated loci in EAs and AAs and further clarify the relationship between FVII and other CVD risk factors