Intrinsic and extrinsic epigenetic age acceleration are associated with hypertensive target organ damage in older African Americans

Abstract Background Epigenetic age acceleration, a measure of biological aging based on DNA methylation, is associated with cardiovascular mortality. However, little is known about its relationship with hypertensive target organ damage to the heart, kidneys, brain, and peripheral arteries. Methods We investigated associations between intrinsic (IEAA) or extrinsic (EEAA) epigenetic age acceleration, blood pressure, and six types of organ damage in a primarily hypertensive cohort of 1390 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. DNA methylation from peripheral blood leukocytes was collected at baseline (1996–2000), and measures of target organ damage were assessed in a follow-up visit (2000–2004). Linear regression with generalized estimating equations was used to test for associations between epigenetic age acceleration and target organ damage, as well as effect modification of epigenetic age by blood pressure or sex. Sequential Oligogenic Linkage Analysis Routines (SOLAR) was used to test for evidence of shared genetic and/or environmental effects between epigenetic age acceleration and organ damage pairs that were significantly associated. Results After adjustment for sex, chronological age, and time between methylation and organ damage measures, higher IEAA was associated with higher urine albumin to creatinine ratio (UACR, p = 0.004), relative wall thickness (RWT, p = 0.022), and left ventricular mass index (LVMI, p = 0.007), and with lower ankle-brachial index (ABI, p = 0.014). EEAA was associated with higher LVMI (p = 0.005). Target organ damage associations for all but IEAA with LVMI remained significant after further adjustment for blood pressure and antihypertensive use (p < 0.05). Further adjustment for diabetes attenuated the IEAA associations with UACR and RWT, and adjustment for smoking attenuated the IEAA association with ABI. No effect modification by age or sex was observed. Conclusions Measures of epigenetic age acceleration may help to better characterize the functional mechanisms underlying organ damage from cellular aging and/or hypertension. These measures may act as subclinical biomarkers for damage to the kidney, heart, and peripheral vasculature; however more research is needed to determine whether these relationships remain independent of lifestyle factors and comorbidities.https://deepblue.lib.umich.edu/bitstream/2027.42/152221/1/12920_2019_Article_585.pd

New Persistent Opioid Use after Outpatient Ureteroscopy for Upper Tract Stone Treatment.

OBJECTIVE: To measure the incidence of persistent opioid use following ureteroscopy (URS). Over 100 Americans die every day from opioid overdose. Recent studies suggest that many opioid addictions surface after surgery. METHODS: Using claims data, we identified adults who underwent outpatient URS for treatment of upper tract stones between January 2008 and December 2016 and filled an opioid prescription attributable to URS. We then measured the rate of new persistent opioid use-defined as continued use of opioids 91 to 180 days after URS among those who were previously opioid-naive. Finally, we fit multivariable models to assess whether new persistent opioid use was associated with the amount of opioid prescribed at the time of URS. RESULTS: In total, 27,740 patients underwent outpatient URS, 51.2% of whom were opioid-naïve. Nearly one in 16 (6.2%) opioid-naïve patients developed new persistent opioid use after URS. Six months following surgery, beneficiaries with new persistent opioid use continued to fill prescriptions with daily doses of 4.2 oral morphine equivalents. Adjusting for measured sociodemographic and clinical differences, patients in the highest tercile of opioids prescribed at the time of URS had 69% higher odds of new persistent opioid use compared to those in the lowest tercile (odds ratio, 1.69; 95% CI, 1.41 to 2.03). CONCLUSIONS: Nearly one in 16 opioid-naive patients develop new persistent opioid use after URS. New persistent opioid use is associated with the amount of opioid prescribed at the time of URS. Given these findings, urologists should re-evaluate their post-URS opioid prescribing patterns