Data are limited regarding statin therapy for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults 75 years and older.
To evaluate the role of statin use for mortality and ...primary prevention of ASCVD in veterans 75 years and older.
Retrospective cohort study that used Veterans Health Administration (VHA) data on adults 75 years and older, free of ASCVD, and with a clinical visit in 2002-2012. Follow-up continued through December 31, 2016. All data were linked to Medicare and Medicaid claims and pharmaceutical data. A new-user design was used, excluding those with any prior statin use. Cox proportional hazards models were fit to evaluate the association of statin use with outcomes. Analyses were conducted using propensity score overlap weighting to balance baseline characteristics.
Any new statin prescription.
The primary outcomes were all-cause and cardiovascular mortality. Secondary outcomes included a composite of ASCVD events (myocardial infarction, ischemic stroke, and revascularization with coronary artery bypass graft surgery or percutaneous coronary intervention).
Of 326 981 eligible veterans (mean SD age, 81.1 4.1 years; 97% men; 91% white), 57 178 (17.5%) newly initiated statins during the study period. During a mean follow-up of 6.8 (SD, 3.9) years, a total 206 902 deaths occurred including 53 296 cardiovascular deaths, with 78.7 and 98.2 total deaths/1000 person-years among statin users and nonusers, respectively (weighted incidence rate difference IRD/1000 person-years, -19.5 95% CI, -20.4 to -18.5). There were 22.6 and 25.7 cardiovascular deaths per 1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -3.1 95 CI, -3.6 to -2.6). For the composite ASCVD outcome there were 123 379 events, with 66.3 and 70.4 events/1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -4.1 95% CI, -5.1 to -3.0). After propensity score overlap weighting was applied, the hazard ratio was 0.75 (95% CI, 0.74-0.76) for all-cause mortality, 0.80 (95% CI, 0.78-0.81) for cardiovascular mortality, and 0.92 (95% CI, 0.91-0.94) for a composite of ASCVD events when comparing statin users with nonusers.
Among US veterans 75 years and older and free of ASCVD at baseline, new statin use was significantly associated with a lower risk of all-cause and cardiovascular mortality. Further research, including from randomized clinical trials, is needed to more definitively determine the role of statin therapy in older adults for primary prevention of ASCVD.
Identification of individuals at highest risk of coronary artery disease (CAD)-ideally before onset-remains an important public health need. Prior studies have developed genome-wide polygenic scores ...to enable risk stratification, reflecting the substantial inherited component to CAD risk. Here we develop a new and significantly improved polygenic score for CAD, termed GPS
, that incorporates genome-wide association data across five ancestries for CAD (>269,000 cases and >1,178,000 controls) and ten CAD risk factors. GPS
strongly associated with prevalent CAD (odds ratio per standard deviation 2.14, 95% confidence interval 2.10-2.19, P < 0.001) in UK Biobank participants of European ancestry, identifying 20.0% of the population with 3-fold increased risk and conversely 13.9% with 3-fold decreased risk as compared with those in the middle quintile. GPS
was also associated with incident CAD events (hazard ratio per standard deviation 1.73, 95% confidence interval 1.70-1.76, P < 0.001), identifying 3% of healthy individuals with risk of future CAD events equivalent to those with existing disease and significantly improving risk discrimination and reclassification. Across multiethnic, external validation datasets inclusive of 33,096, 124,467, 16,433 and 16,874 participants of African, European, Hispanic and South Asian ancestry, respectively, GPS
demonstrated increased strength of associations across all ancestries and outperformed all available previously published CAD polygenic scores. These data contribute a new GPS
for CAD to the field and provide a generalizable framework for how large-scale integration of genetic association data for CAD and related traits from diverse populations can meaningfully improve polygenic risk prediction.
Multiple genetic loci have been convincingly associated with the risk of type 2 diabetes mellitus. We tested the hypothesis that knowledge of these loci allows better prediction of risk than ...knowledge of common phenotypic risk factors alone.
We genotyped single-nucleotide polymorphisms (SNPs) at 18 loci associated with diabetes in 2377 participants of the Framingham Offspring Study. We created a genotype score from the number of risk alleles and used logistic regression to generate C statistics indicating the extent to which the genotype score can discriminate the risk of diabetes when used alone and in addition to clinical risk factors.
There were 255 new cases of diabetes during 28 years of follow-up. The mean (+/-SD) genotype score was 17.7+/-2.7 among subjects in whom diabetes developed and 17.1+/-2.6 among those in whom diabetes did not develop (P<0.001). The sex-adjusted odds ratio for diabetes was 1.12 per risk allele (95% confidence interval, 1.07 to 1.17). The C statistic was 0.534 without the genotype score and 0.581 with the score (P=0.01). In a model adjusted for sex and self-reported family history of diabetes, the C statistic was 0.595 without the genotype score and 0.615 with the score (P=0.11). In a model adjusted for age, sex, family history, body-mass index, fasting glucose level, systolic blood pressure, high-density lipoprotein cholesterol level, and triglyceride level, the C statistic was 0.900 without the genotype score and 0.901 with the score (P=0.49). The genotype score resulted in the appropriate risk reclassification of, at most, 4% of the subjects.
A genotype score based on 18 risk alleles predicted new cases of diabetes in the community but provided only a slightly better prediction of risk than knowledge of common risk factors alone.
Context: Metabolic risk conferred by adiposity may be due to associated risk factor clustering.
Objective: The objective of this study was to assess risk for diabetes or cardiovascular disease (CVD) ...stratified by body mass index (BMI) and the presence or absence of metabolic syndrome (MetS) or insulin resistance (IR).
Design, Setting, and Participants: This was a community-based, longitudinal study of 2902 people (55% women, mean age 53 yr) without diabetes or CVD in 1989–1992 followed for up to 11 yr. We categorized subjects by normal weight (BMI < 25 kg/m2), overweight (25–29.9 kg/m2), or obese (>30 kg/m2) and by the National Cholesterol Education Program’s Adult Treatment Panel MetS or the top quartile of homeostasis model IR. We used proportional hazard models to estimate risk relative to normal weight and no MetS or IR.
Main Outcome Measure: Incident type 2 diabetes (treatment or fasting glucose ≥ 7 mmol/liter, 141 events) or CVD (myocardial infarction, stroke, or claudication, 252 events) were measured.
Results: Among 1056 normal-weight subjects, 7% had MetS and a risk factor-adjusted relative risk for diabetes of 3.97 (95% confidence interval, 1.35–11.6) and for CVD of 3.01 (1.68–5.41). Among 638 obese subjects, 37% did not have MetS or significantly increased risk. Obese subjects with MetS had an adjusted relative risk for diabetes of 10.3 (5.44–19.5) and for CVD of 2.13 (1.43–3.18). Results were similar in analyses of BMI-IR categories.
Conclusions: People with normal weight and MetS or IR or with obesity but no MetS or IR were not uncommon in our sample. Risk factor clustering or IR appear to confer much of the risk for diabetes or CVD commonly associated with elevated BMI.
Certain
strains residing in the human gut produce colibactin, a small-molecule genotoxin implicated in colorectal cancer pathogenesis. However, colibactin's chemical structure and the molecular ...mechanism underlying its genotoxic effects have remained unknown for more than a decade. Here we combine an untargeted DNA adductomics approach with chemical synthesis to identify and characterize a covalent DNA modification from human cell lines treated with colibactin-producing
Our data establish that colibactin alkylates DNA with an unusual electrophilic cyclopropane. We show that this metabolite is formed in mice colonized by colibactin-producing
and is likely derived from an initially formed, unstable colibactin-DNA adduct. Our findings reveal a potential biomarker for colibactin exposure and provide mechanistic insights into how a gut microbe may contribute to colorectal carcinogenesis.
Background Diabetes mellitus is a risk factor for cardiovascular disease ( CVD ) and has been associated with 2- to 4-fold higher mortality. Diabetes mellitus-related mortality has not been ...reassessed in individuals receiving routine care in the United States in the contemporary era of CVD risk reduction. Methods and Results We retrospectively studied 963 648 adults receiving care in the US Veterans Affairs Healthcare System from 2002 to 2014; mean follow-up was 8 years. We estimated associations of diabetes mellitus status and hemoglobin A1c (HbA1c) with all-cause and CVD mortality using covariate-adjusted incidence rates and multivariable Cox proportional hazards regression. Of participants, 34% had diabetes mellitus. Compared with nondiabetic individuals, patients with diabetes mellitus had 7.0 (95% CI , 6.7-7.4) and 3.5 (95% CI, 3.3-3.7) deaths/1000-person-years higher all-cause and CVD mortality, respectively. The age-, sex-, race-, and ethnicity-adjusted hazard ratio for diabetes mellitus-related mortality was 1.29 (95% CI, 1.28-1.31), and declined with adjustment for CVD risk factors (hazard ratio, 1.18 95% CI, 1.16-1.19) and glycemia (hazard ratio, 1.03 95% CI, 1.02-1.05). Among individuals with diabetes mellitus, CVD mortality increased as HbA1c exceeded 7% (hazard ratios, 1.11 95% CI, 1.08-1.14, 1.25 95% CI, 1.22-1.29, and 1.52 95% CI, 1.48-1.56 for HbA1c 7%-7.9%, 8%-8.9%, and ≥9%, respectively, relative to HbA1c 6%-6.9%). HbA1c 6% to 6.9% was associated with the lowest mortality risk irrespective of CVD history or age. Conclusions Diabetes mellitus remains significantly associated with all-cause and CVD mortality, although diabetes mellitus-related excess mortality is lower in the contemporary era than previously. We observed a gradient of mortality risk with increasing HbA1c >6% to 6.9%, suggesting HbA1c remains an informative predictor of outcomes even if causality cannot be inferred.
Ice repellent coatings have been studied and keenly sought after for many years, where any advances in the durability of such coatings will result in huge energy savings across many fields. Progress ...in creating anti-ice and anti-frost surfaces has been particularly rapid since the discovery and development of slippery, liquid infused porous surfaces (SLIPS). Here we use SLIPS-coated differential scanning calorimeter (DSC) pans to investigate the effects of the surface modification on the nucleation of supercooled water. This investigation is inherently different from previous studies which looked at the adhesion of ice to SLIPS surfaces, or the formation of ice under high humidity conditions. Given the stochastic nature of nucleation of ice from supercooled water, multiple runs on the same sample are needed to determine if a given surface coating has a real and statistically significant effect on the nucleation temperature. We have cycled supercooling to freezing and then thawing of deionized water in hydrophilic (untreated aluminum), hydrophobic, superhydrophobic, and SLIPS-treated DSC pans multiple times to determine the effects of surface treatment on the nucleation and subsequent growth of ice. We find that SLIPS coatings lower the nucleation temperature of supercooled water in contact with statistical significance and show no deterioration or change in the coating performance even after 150 freeze-thaw cycles.
Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 17% of national health expenditures. As the population ages, these costs are expected to ...increase substantially.
To prepare for future cardiovascular care needs, the American Heart Association developed methodology to project future costs of care for hypertension, coronary heart disease, heart failure, stroke, and all other CVD from 2010 to 2030. This methodology avoided double counting of costs for patients with multiple cardiovascular conditions. By 2030, 40.5% of the US population is projected to have some form of CVD. Between 2010 and 2030, real (2008$) total direct medical costs of CVD are projected to triple, from $273 billion to $818 billion. Real indirect costs (due to lost productivity) for all CVD are estimated to increase from $172 billion in 2010 to $276 billion in 2030, an increase of 61%.
These findings indicate CVD prevalence and costs are projected to increase substantially. Effective prevention strategies are needed if we are to limit the growing burden of CVD.
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