Use Of Cholesterol-lowering Medications Research Articles

Abstract P540: Sleep Duration, Rapid Eye Movement Sleep, and Subclinical Myocardial Damage

Introduction: Sleep is strongly linked to clinical cardiovascular disease and was added in 2022 to the AHA’s Life’s Essential 8. Optimizing sleep duration and quality may reduce the risk of cardiovascular disease. Few studies have examined self-reported sleep duration and percent time in rapid eye movement (REM) sleep measured by single night in-home polysomnography with high sensitivity cardiac troponin T (hs-troponin T), a biomarker of subclinical cardiovascular disease. Methods: We conducted a cross-sectional study of adults without a history of cardiovascular disease who participated in both the Atherosclerosis Risk in Communities (ARIC) Study and the Sleep Heart Health Study (SHHS) in 1995-1998. We used linear regression with sleep duration and percentage time of REM sleep modeled as predictors with restricted cubic splines and examined associations with the outcome, hs-troponin T. We adjusted for age, sex, body mass index, waist-to-hip ratio, alcohol intake, smoking status, systolic blood pressure, hypertension medication use, diabetes, HDL- and LDL-cholesterol, and cholesterol-lowering medication use. Results: Among 1,587 participants (mean age 63, 54% female), the mean sleep duration was 7.3 hours, and mean % REM time was 20.7. Sleep duration was not associated with hs-troponin T ( Figure, Panel A ). However, percentage REM sleep was negatively associated with hs-troponin T, but with a threshold effect; there was a negative linear association of hs-troponin T with % REM sleep but only at values <15% ( Figure, Panel B ). Conclusion: While self-reported sleep duration was not associated with TnT levels, there was evidence that low % REM sleep, a specific neurophysiological sleep state, was associated with subclinical cardiovascular disease. These findings suggest that multiple sleep dimensions should be considered in efforts to optimize cardiovascular health.

EGG CONSUMPTION: TRENDS OVER TIME, PATTERNS ACROSS THE LIFESPAN, AND PREDICTORS OF INTAKE

Abstract Eggs are an excellent nutritional source. However, the historical association of dietary cholesterol with serum cholesterol and thus, cardiovascular disease, along with restrictive dietary guidelines may have served as a barrier to egg consumption. This study examines trends over time, and predictors and patterns of egg consumption in older individuals followed for over 45 years. Participants were 6326 men and women enrolled in the Rancho Bernardo Study in 1972-74 when they were asked about the number of eggs consumed/week. Subsequent egg intake information was collected with food frequency questionnaires from subsamples attending clinic visits in 1988-91 (N=1627) and 1992-96 (N=1385), and with the original question on a 2021 mailed survey (N=710). Mean(□SD) eggs consumed was 3.6□3.0 in 1972-74, 1.8□2.1 in 1988-91, 1.8□2.2 in 1992-96, and 3.4□3.5 in 2021. Comparisons within 5-year categories of baseline age (< 20, 20-24, 25-29, 30-34, 35-39, >40) showed no differences in egg intake between 1972-74 and when older in 2021. Men consumed more eggs than women at all timepoints (p’s< 0.0001). Those with higher education (p< 0.0001) and diabetes (p=0.0009) consumed more eggs; those with high cholesterol or taking cholesterol lowering medication consumed fewer eggs in 1972-74 (p’s< 0.0001), but there were no differences by these factors by 2021. Egg consumption appears responsive to dietary guidelines, decreasing over time then increasing by 2021 to levels similar to the early 1970s. Among those young and middle-aged at baseline, egg intake patterns were similar 45 years later, when older. Cholesterol and cholesterol-lowering medication use are no longer factors in egg intake.

Relationship Between Diet Quality and Statin Use Among Adults With Metabolic Syndrome From the CARTaGENE Cohort

BackgroundIn metabolic syndrome (MetS), cardiovascular disease (CVD) risk reduction relies on the complementary use of diet and lipid-lowering medication. Evidence suggests that initiating such medication may impede diet quality. The objective of this study was to evaluate the relationship between diet quality and statin use among adults with MetS and free of CVD from the Province of Québec. MethodsThis cross-sectional study included 2481 adults with MetS (40-69 years of age) from the CARTaGENE Québec population-based cohort, of whom 463 self-reported using statin monotherapy. Diet was assessed using the Canadian Dietary History Questionnaire II, a food- frequency questionnaire, and diet quality was assessed using the Alternative Healthy Eating Index (AHEI). ResultsIn multivariable-adjusted linear regression models, statin users had lower AHEI (%) compared with nonusers (users: 40.0; 95% confidence interval [CI], 38.9, 41.2 vs nonusers: 41.2; 95% CI, 40.4, 42.0; P = 0.03] because of a lower consumption of vegetables and whole grains. Stratified interaction analyses showed that the lower diet quality among statin users was mostly prevalent among men aged ≥ 50 years and women aged ≥ 60 years, among individuals with annual household incomes of < $50,000 and persons who self-reported history of high blood pressure. ConclusionsIn this cohort of adults with MetS from Quebéc, the use of statin monotherapy in primary prevention of CVD was associated with a slightly lower diet quality. These data suggest suboptimal complementarity between diet quality and use of cholesterol-lowering medication in primary prevention of CVD in MetS.

Former long-term use of combined hormonal contraception and glucose metabolism disorders in perimenopausal women: A prospective, population-based cohort study.

Current use of combined hormonal contraceptives worsens glucose tolerance and increases the risk of type 2 diabetes mellitus at late fertile age, but the impact of their former use on the risk of glucose metabolism disorders is still controversial. This was a prospective, longitudinal birth cohort study with long-term follow-up consisting of 5889 women. The cohort population has been followed at birth, and at ages of 1, 14, 31 and 46. In total, 3280 (55.7%) women were clinically examined and 2780 also underwent a 2-h oral glucose tolerance test at age 46. Glucose metabolism indices were analyzed in former combined hormonal contraceptive users (n = 1371) and former progestin-only contraceptive users (n = 52) and in women with no history of hormonal contraceptive use (n = 253). Compared with women with no history of hormonal contraceptive use, those who formerly used combined hormonal contraceptives for over 10 years had an increased risk of prediabetes (odds ratio [OR] 3.9, 95% confidence interval [CI]: 1.6-9.2) but not of type 2 diabetes mellitus. Former progestin-only contraceptive use was not associated with any glucose metabolism disorders. The results persisted after adjusting for socioeconomic status, smoking, alcohol consumption, parity, body mass index and use of cholesterol-lowering medication. Former long-term use of combined hormonal contraceptives was associated with a significantly increased risk of prediabetes in perimenopausal women, which potentially indicates a need of screening for glucose metabolism disorders in these women.

#5650 METABOLIC BLOOD BIOMARKER PROFILING FOR CHRONIC KIDNEY DISEASE PREDICTION – EVIDENCE FROM 275,000 INDIVIDUALS IN THE UK BIOBANK

Abstract Background and Aims Early identification of individuals at high risk of developing chronic kidney disease and other chronic conditions is essential for targeted prevention. Here, we assess the utility of metabolic blood biomarkers in predicting the onset of chronic kidney disease in over 250,000 individuals from UK Biobank, beyond established risk factors and polygenic risk scores. Method Circulating blood biomarkers, including lipids, fatty acids, amino acids, glycolysis metabolites and inflammation markers were measured by a low-cost nuclear magnetic resonance (NMR) metabolomics assay in around 275,000 plasma samples from the UK Biobank. During a prospective 10-year follow-up, over 6000 incident chronic kidney disease events were obtained from national health registries. Using multivariable regression modelling, we derived a 10-year risk score for chronic kidney disease onset. We assessed the predictive performance of the biomarker risk score in comparison to standard risk factors (age, sex, prevalent diabetes, body mass index, systolic and diastolic blood pressure, smoking status and use of cholesterol lowering medication), clinical chemistry measurements (HbA1c, LDL and HDL cholesterol, total cholesterol and eGFR) and polygenic risk scores. We evaluated the performance of the risk score in two practical scenarios: in a general population screening setting and in a clinical use case of stratifying kidney disease risk among prevalent type 2 diabetics. We further illustrate applications of the biomarker risk scores in predicting the risk of other chronic diseases, such as cardiovascular outcomes, in general population settings. Results In the general population screening setting, adding the metabolic biomarkers to a simple model of standard risk factors substantially improved the predictive performance, with area under the receiver operating characteristic curve (AUC) increasing from 0.74 to 0.82. When compared to more comprehensive model including also clinical chemistry measurements and polygenic risk scores, the improvements were also significant, albeit more modest, with the AUC increasing from 0.81 to 0.83. Even more substantial gains were observed in a clinical use case scenario of stratifying risk of chronic kidney disease onset among prevalent type 2 diabetics. Among diabetics with mildly to moderately decreased kidney function at the time of blood sampling (eGFR 60-90), adding the metabolic biomarkers in a comprehensive model including standard risk factors, clinical chemistry measurements and polygenic risk scores increased the AUC from 0.60 to 0.70. Conclusion Circulating metabolic biomarkers enhanced the prediction of chronic kidney disease onset beyond standard risk factors and polygenic risk scores. From a translational perspective, this may complement the identification of high-risk individuals in both general population and clinical settings beyond current risk factor assessment, while simultaneously informing on the risk of other chronic diseases.

Selected Articles from This Issue

Highlights| April 03 2023 Selected Articles from This Issue Author & Article Information Online ISSN: 1538-7755 Print ISSN: 1055-9965 ©2023 American Association for Cancer Research2023American Association for Cancer Research Cancer Epidemiol Biomarkers Prev (2023) 32 (4): 463. https://doi.org/10.1158/1055-9965.EPI-32-4-HI Related Content A commentary has been published: Risk of Renal or Urinary Related Hospitalization in Survivors of Childhood Cancer: Results from the French Childhood Cancer Survivor Study A commentary has been published: Serum Lipid Profiles and Cholesterol-Lowering Medication Use in Relation to Subsequent Risk of Colorectal Cancer in the UK Biobank Cohort A commentary has been published: The Intersectionality between Race, Ethnicity, and Residential-Level Socioeconomic Status in Disparities of Head and Neck Cancer Outcomes: A SEER Study View more A commentary has been published: Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma View less Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Article Versions Icon Versions Version of Record April 3 2023 Citation Selected Articles from This Issue. Cancer Epidemiol Biomarkers Prev 1 April 2023; 32 (4): 463. https://doi.org/10.1158/1055-9965.EPI-32-4-HI Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest Search Advanced Search Head and Neck cancer mortality differs by race/ethnicity and socioeconomic status (SES). In this study of 76,095 patients, Karanth and colleagues examined the joint association of race/ethnicity and census-tract-level SES with relative survival rates, all-cause and cause-specific mortality. The five-year survival rates differed by race/ethnicity and SES, with non-Hispanic (NH)-Black patients having the lowest. Compared to NH-White patients, NH-Black patients had a higher risk of all-cause and cause-specific mortality, regardless of the SES group. NH-Asian/Pacific Islander and Hispanic patients had higher risk of cause-specific mortality in some SES groups. More research is needed to understand the causes of persistent disparities in head and neck cancer mortalities Most previous epidemiologic studies evaluating the associations of blood lipids with colorectal cancer risk did not consider the use of cholesterol-lowering medications at the time of lipid measurements, which could bias findings. Leveraging data from the UK Biobank, Yuan and colleagues showed that high... You do not currently have access to this content.

Genetic and clinical factors underlying a self-reported family history of heart disease.

To estimate how much information conveyed by self-reported family history of heart disease (FHHD) is already explained by clinical and genetic risk factors. Cross-sectional analysis of UK Biobank participants without pre-existing coronary artery disease using a multivariable model with self-reported FHHD as the outcome. Clinical (diabetes, hypertension, smoking, apolipoprotein B-to-apolipoprotein AI ratio, waist-to-hip ratio, high sensitivity C-reactive protein, lipoprotein(a), triglycerides) and genetic risk factors (polygenic risk score for coronary artery disease [PRSCAD], heterozygous familial hypercholesterolemia [HeFH]) were exposures. Models were adjusted for age, sex, and cholesterol-lowering medication use. Multiple logistic regression models were fitted to associate FHHD with risk factors, with continuous variables treated as quintiles. Population attributable risks (PAR) were subsequently calculated from the resultant odds ratios. Among 166 714 individuals, 72 052 (43.2%) participants reported an FHHD. In a multivariable model, genetic risk factors PRSCAD (OR 1.30, CI 1.27-1.33) and HeFH (OR 1.31, 1.11-1.54) were most strongly associated with FHHD. Clinical risk factors followed: hypertension (OR 1.18, CI 1.15-1.21), lipoprotein(a) (OR 1.17, CI 1.14-1.20), apolipoprotein B-to-apolipoprotein AI ratio (OR 1.13, 95% CI 1.10-1.16), and triglycerides (OR 1.07, CI 1.04-1.10). For the PAR analyses: 21.9% (CI 18.19-25.63) of the risk of reporting an FHHD is attributed to clinical factors, 22.2% (CI% 20.44-23.88) is attributed to genetic factors, and 36.0% (CI 33.31-38.68) is attributed to genetic and clinical factors combined. A combined model of clinical and genetic risk factors explains only 36% of the likelihood of FHHD, implying additional value in the family history.

Abstract P629: Influenza Vaccine Uptake is Associated With Cholesterol Treatment Adherence: An Analysis of the Behavioral Risk Factor Surveillance System Survey

Introduction: Misinformation, distrust, and other sociocultural factors that influence vaccine uptake may also influence adherence to cholesterol treatment. Hypothesis: Among American adults with hyperlipidemia, individuals who receive influenza vaccination are more likely to report use of cholesterol lowering medication. Methods: We pooled 2017 and 2019 survey data from the Behavioral Risk Factor Surveillance System (BRFSS). Our sample included all respondents aged 40 to 75 years with self-reported high cholesterol. We used logistic regression models adjusted for potential confounders to examine the association between influenza vaccine uptake and use of cholesterol medication. We also evaluated whether the association was different among those with and without established atherosclerotic cardiovascular disease (ASCVD). All analyses accounted for survey weighting. Results: Of 228,338 (weighted = 107,893,277) participants with hyperlipidemia, 51% reported influenza vaccination and 61% reported taking cholesterol medication. Vaccine uptake was associated with cholesterol medication use (OR 2.08, 95% CI 2.00-2.16, p &lt;0.001). Although slightly attenuated, this association persisted after adjustment for socio-demographics, access to care, comorbidities, and adherence to hypertension treatment (OR 1.53, 95% CI 1.42-1.65, p-value &lt;0.001). The association was similar in those with ASCVD (OR 1.63, 95% CI 1.32-2.03, p-value &lt;0.001) and those without ASCVD (OR 1.52, 95% CI 1.40-1.64, p-value &lt;0.001), p-value for interaction = 0.89. Conclusions: Influenza vaccine uptake is associated with cholesterol medication use among American adults with high cholesterol, including those with ASCVD. The sociocultural factors affecting vaccine avoidance, such as misinformation and distrust, merit investigation as potential targets of cardiovascular prevention efforts.

Serum Lipid Profiles and Cholesterol-Lowering Medication Use in Relation to Subsequent Risk of Colorectal Cancer in the UK Biobank Cohort.

Dyslipidemia is closely associated with metabolic syndrome, a known risk factor for colorectal cancer. However, the association of dyslipidemia with colorectal cancer risk is controversial. Most previous studies did not consider cholesterol-lowering medication use at the time of lipid measurements, which could bias findings. We analyzed data from 384,862 UK Biobank participants to disentangle the associations between blood lipids and colorectal cancer risk. Serum levels of total cholesterol, high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglyceride were measured at study baseline. Multivariable-adjusted Cox models were used to estimate HRs and 95% confidence intervals (CI). During a median follow-up time of 8.2 years, 3,150 incident primary colorectal cancer cases were identified. Triglyceride levels were positively, while HDL-C levels were inversely associated with colorectal cancer risk (both Ptrend < 0.005). No significant associations were found for total cholesterol and LDL-C. However, among nonusers of cholesterol-lowering medications, a high total cholesterol level (> 6.7 mmol/L, HR = 1.11; 95% CI, 1.00-1.24) and LDL-C level (>4.1 mmol/L, HR = 1.11; 95% CI, 0.99-1.23) was associated with an increased colorectal cancer risk compared with the referent group (5.2-6.2 mmol/L and 2.6-3.4 mmol/L for total and LDL cholesterol, respectively). Compared with nonusers, cholesterol-lowering medication users had 15% increased colorectal cancer risk (HR = 1.15; 95% CI, 1.04-1.26). Circulating total cholesterol, LDL-C, HDL-C and triglyceride were modestly associated with colorectal cancer risk. Our findings call for careful consideration of cholesterol-lowering medication use in future studies of blood lipid-colorectal cancer associations.

Association between sociodemographic factors and cholesterol-lowering medication use in U.S. adults post-myocardial infarction.

Cholesterol-lowering medications offer effective secondary prevention after myocardial infarction (MI). Our objective was to evaluate the association between sociodemographic factors and cholesterol-lowering medication use in high-risk adults. We conducted an analysis using weighted data from 31,408 participants in the 2017 and 2019 Behavioral Risk Factor Surveillance Systems cross-sectional surveys, who had a self-reported history of MI and high blood cholesterol. The sociodemographic factors evaluated were sex, age, race and ethnicity, annual household income, education level, relationship status, and reported healthcare coverage. We estimated the weighted prevalence of medication use, and weighted prevalence differences (with 95% confidence intervals) across categories, adjusting for sex, age group, healthcare coverage, smoking status, hypertension, and diabetes. Overall, 83% of survey participants with a self-reported history of both MI and high blood cholesterol reported currently using a cholesterol-lowering medication. The prevalence of use was only 61% in those without self-reported healthcare coverage, compared to 85% of those with healthcare coverage (adjusted prevalence difference of -20%; 95% CI: -25% to -14%). Use of cholesterol-lowering medication was relatively low in younger adults and higher in older adults, leveling off after age 65 years. The proportion of Native Hawaiian or Pacific Islanders who were using a cholesterol-lowering medication was relatively low, but otherwise there was little variation by race and ethnicity. Household income, education level, and relationship status were weakly or not associated with medication use. Knowledge of characteristics of persons who are relatively less likely to be adherent with cholesterol-lowering medications for secondary prevention may be useful to policymakers and healthcare providers involved in the long-term treatment of MI patients. Policy makers might consider a reduced cost prescription coverage for persons without current healthcare coverage who have sustained an MI to reduce future cardiovascular morbidity and mortality.

Incidence of erectile dysfunction treatment after radical prostatectomy by Statin use in Finnish Nationwide Cohort Study

Background Erectile dysfunction (ED) is common after radical prostatectomy (RP) due to cavernous nerve damage. Risk of ED is also affected by vascular function. Statins prevent vascular events but their association with post-prostatectomy ED is unclear. We explored the likelihood of starting ED treatment after RP by statin use at the population level. Methods The study cohort included 14,295 prostate cancer (PCa) patients with no ED treatment prior to diagnosis of PCa treated with RP in Finland during 1995–2013. Information on use of cholesterol-lowering drugs and ED medication during 1995–2014 and penile prosthesis implantation during 1996–2014 were gathered from national registries. Risk of ED treatment initiation after RP was analyzed by pre-diagnostic and post-diagnostic statin and non-statin cholesterol lowering (NSCL) drug use with Cox regression model. Results Pre-diagnostic statin use or NSCL drug use overall had no association with risk of ED treatment initiation after RP. Post-diagnostic statin use was associated with a slightly increased risk of initiation of any ED treatment (HR = 1.07; 95% CI = 1.01–1.14). Patients with the longest duration of post-diagnostic statin use had a significantly decreased risk of PDE5 inhibitor initiation compared to non-users (HR = 0.43; 95% CI = 0.20–0.94). Among patients with no cardiovascular comorbidities, pre-diagnostic statin users had a significantly increased risk of initiation of injectable ED drugs (HR = 1.27; 95% CI = 1.04–1.55), however, no association with risk of any other ED treatment was observed. Conclusion Statin users have a slightly increased risk of ED treatment initiation after RP, which probably reflects the effect of the underlying vascular insufficiency.

Associations between mercury exposure with blood pressure and lipid levels: A cross-sectional study of dental professionals

Mercury (Hg) exposure is a public health problem worldwide that is now being addressed through the Minamata Convention on Mercury. Fish containing methylmercury and dental amalgam containing elemental Hg are the major sources of exposure for most populations. There is some evidence that methylmercury impacts cardiovascular and metabolic health, primarily in populations with high exposure levels. Studies of elemental Hg and these outcomes are relatively rare. We aimed to examine associations between Hg exposure (both elemental and methylmercury) and blood pressure, as well as cholesterol and triglyceride levels. In 2012, we recruited dental professionals attending the Health Screening Program at the American Dental Association (ADA) Annual Session in California. Total Hg levels in hair and blood samples were analyzed as indicators of methylmercury exposure and in urine as an indicator of primarily elemental Hg exposure (n = 386; mean ± sd age 55 ± 11 years). We measured blood pressure (systolic and diastolic) and lipid profiles (total cholesterol, high-density lipoprotein cholesterol [HDL], low-density lipoprotein cholesterol [LDL] and triglycerides). The geometric means (geometric standard deviations) for blood, hair, and urine Hg were 3.64 (2.39) μg/L, 0.60 (2.91) μg/g, and 1.30 (2.44) μg/L, respectively. For every one μg/L increase in specific gravity-adjusted urine Hg, LDL increased by 2.31 mg/dL (95% CI = 0.09, 4.54), in linear regression adjusting for BMI, race, sex, polyunsaturated fatty acid intake from fish consumption, smoking status, and use of cholesterol-lowering medication. No significant associations between Hg biomarkers and blood pressure or hair or blood Hg with lipid levels were observed. Results suggest that elemental Hg exposure may influence LDL concentrations in adults with low-level exposure, and this relationship merits further study in other populations.

Total protein intake and subsequent risk of chronic kidney disease: the Circulatory Risk in Communities Study.

Whether dietary protein intake worsens renal function in the general population has been discussed but not yet determined. We aimed to examine the longitudinal association between dietary protein intake and risk of incident chronic kidney disease (CKD). We conducted a 12-year follow-up study with 3,277 Japanese adults (1,150 men and 2,127 women) aged 40-74 years, initially free from CKD, who participated in cardiovascular risk surveys from two Japanese communities under the Circulatory Risk in Communities Study. The development of CKD was defined by the estimated glomerular filtration rate (eGFR) during the follow-up period. Protein intake was measured at baseline by using the brief-type self-administered diet history questionnaire. We estimated sex-, age-, community- and multivariate-adjusted hazard ratios (HR) for incident CKD were calculated using the Cox proportional hazards regression models according to quartiles of percentage of energy (%energy) from protein intake. During 26,422 person-years of follow-up, 300 participants developed CKD (137 men and 163 women). The sex-, age-, and community-adjusted HR (95% confidence interval, CI) for the highest (≥16.9%energy) versus lowest (≤13.4%energy) quartiles of total protein intake was 0.66 (0.48-0.90), p for trend = 0.007. The multivariable HR (95%CI) was 0.72 (0.52-0.99), p for trend = 0.016 after further adjustment for body mass index, smoking status, alcohol drinking status, diastolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol levels, cholesterol-lowering medication use, total energy intake, and baseline eGFR. The association did not vary by sex, age, and baseline eGFR. When examining animal and vegetable protein intake separately, the respective multivariable HRs (95%CIs) were 0.77 (0.56-1.08), p for trend = 0.036, and 1.24 (0.89-1.75), p for trend = 0.270. Higher protein intake, more specifically animal protein intake was associated with a lower risk of CKD.

What should be the goal of cholesterol-lowering treatment? A quantitative evaluation dispelling guideline myths.

Guidelines for cholesterol-lowering treatment generally include extensive review of epidemiological and clinical trial evidence. However, the next logical step, the translation of evidence into clinical advice, occurs not entirely by reasoning, but by a form of consensus in which the prejudices and established beliefs of the societies with interests in cardiovascular disease convened to interpret the evidence are prominent. Methods, which are the subject of this review, have, however, been developed by which clinical trial evidence can be translated objectively into best practice. Guidelines differ in their recommended goals for cholesterol-lowering treatment in the prevention of atherosclerotic cardiovascular disease (ASCVD). Proposed goals are LDL-cholesterol 2.6 mmol/l (100 mg/dl) or less in lower risk, LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less in higher risk, non-HDL-cholesterol decrease of at least 40% or LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less or decreased by at least 50% whichever is lower. Evidence from clinical trials of statins, ezetimibe and proprotein convertase subtilisin/kexin type 9-inhibitors can be expressed in simple mathematical terms to compare the efficacy on ASCVD incidence of clinical guidance for the use of cholesterol-lowering medication. The target LDL-cholesterol of 2.6 mmol/l (100 mg/dl) is ineffective and lacks credibility. Cholesterol-lowering medication is most effective in high-risk people with raised LDL-cholesterol. The best overall therapeutic target is LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less or decreased by at least 50% whichever is lower. The use of non-HDL-cholesterol as a therapeutic goal is less efficacious. Aiming for LDL-cholesterol 1.4 mmol/l (55 mg/dl) or less as opposed to 1.8 mmol/l produces only a small additional benefit. Evidence for apolipoprotein B targets in hypertriglyceridaemia and in very high ASCVD risk should be more prominent in future guidelines. The LDL-cholesterol goal of 2.6 mmol/l or less should be abandoned. Percentage decreases in LDL-cholesterol or non-HDL-cholesterol concentration are better in people with initial concentrations of less than 3.6 mmol/l. The LDL-cholesterol target of 1.8 mmol/l is most effective when initial LDL-cholesterol is more than 3.6 mmol/l in both primary and secondary prevention.

LDL cholesterol is associated with higher AD neuropathology burden independent of APOE

ObjectiveAPOE is a strong risk factor for Alzheimer’s disease (AD) and associated with higher low-density lipoprotein cholesterol (LDL-C) levels. Moreover, LDL-C is associated with the development of clinically ascertained AD;...

Cholesterol-Lowering Medication Use Prior to Ischemic Strokes Secondary to Large Artery Atherosclerosis or Small Vessel Disease: A Single Center Study (S35.009)

Cholesterol-Lowering Medication Use Prior to Ischemic Strokes Secondary to Large Artery Atherosclerosis or Small Vessel Disease: A Single Center Study (S35.009)

Clinical and Lifestyle-Related Prognostic Indicators among Esophageal Adenocarcinoma Patients Receiving Treatment at a Comprehensive Cancer Center.

Simple SummaryEsophageal adenocarcinoma (EAC) is a highly lethal cancer with rising incidence in Western countries. Despite diagnostic and therapeutic advances, average 5-year EAC survival remains poor (~20%), with tumor stage and treatment the strongest prognostic factors. The role of lifestyle-related exposures remains uncertain. To address this gap, we analyzed survival associations among EAC patients treated at a tertiary cancer center. Importantly, this study is among the first to assess survival relationships by disease stage for several key lifestyle-related exposures (e.g., physical activity, medications, and diet), enabling us to identify associations which may have been obscured in past analyses. Our findings suggest that lifestyle interventions such as smoking cessation, exercise regimens, and use of cholesterol-lowering (statin) or anti-inflammatory (NSAID) medications may represent promising avenues to improve outcomes in this deadly cancer.Purpose: The incidence of esophageal adenocarcinoma (EAC) has risen substantially in recent decades, while the average 5-year survival remains only ~20%. Disease stage and treatment are the strongest prognostic factors. The role of lifestyle factors in relation to survival remains uncertain, with a handful of studies to date investigating associations with obesity, smoking, physical activity, diet, or medications. Methods: This study included patients diagnosed with primary adenocarcinoma of the esophagus, gastroesophageal junction, or cardia (N = 371) at Roswell Park Comprehensive Cancer Center between 2003 and 2019. Leveraging extensive data abstracted from electronic medical records, epidemiologic questionnaires, and a tumor registry, we analyzed clinical, behavioral, and environmental exposures and evaluated stage-specific associations with survival. Survival distributions were visualized using Kaplan–Meier curves. Cox proportional hazards regression models adjusted for age, sex, stage, treatment, and comorbidities were used to estimate the association between each exposure and all-cause or cancer-specific mortality. Results: Among patients presenting with localized/regional tumors (stages I–III), current smoking was associated with increased overall mortality risk (HR = 2.5 [1.42–4.53], p = 0.002), while current physical activity was linked to reduced risk (HR = 0.58 [0.35–0.96], p = 0.035). Among patients with stage IV disease, individuals reporting pre-diagnostic use of statins (HR = 0.62 [0.42–0.92], p = 0.018) or NSAIDs (HR = 0.61 [0.42–0.91], p = 0.016) had improved overall survival. Exploratory analyses suggested that high pre-diagnostic dietary consumption of broccoli, carrots, and fiber correlated with prolonged overall survival in patients with localized/regional disease. Conclusion: Our data suggest that lifestyle exposures may be differentially associated with EAC survival based on disease stage. Future investigation of larger, diverse patient cohorts is essential to validate these findings. Our results may help inform the development of lifestyle-based interventions to improve EAC prognosis and quality of life.

Associations of systemic health and medication use with the enlargement rate of geographic atrophy in age-related macular degeneration

BackgroundThe associations of geographic atrophy (GA) progression with systemic health status and medication use are unclear.MethodsWe manually delineated GA in 318 eyes in the Age-Related Eye Disease Study. We calculated...

Derivation and Validation of a 10-Year Risk Score for Symptomatic Abdominal Aortic Aneurysm: Cohort Study of Nearly 500 000 Individuals.

Abdominal aortic aneurysm (AAA) can occur in patients who are ineligible for routine ultrasound screening. A simple AAA risk score was derived and compared with current guidelines used for ultrasound screening of AAA. United Kingdom Biobank participants without previous AAA were split into a derivation cohort (n=401 820, 54.6% women, mean age 56.4 years, 95.5% White race) and validation cohort (n=83 816). Incident AAA was defined as first hospital inpatient diagnosis of AAA, death from AAA, or an AAA-related surgical procedure. A multivariable Cox model was developed in the derivation cohort into an AAA risk score that did not require blood biomarkers. To illustrate the sensitivity and specificity of the risk score for AAA, a theoretical threshold to refer patients for ultrasound at 0.25% 10-year risk was modeled. Discrimination of the risk score was compared with a model of US Preventive Services Task Force (USPSTF) AAA screening guidelines. In the derivation cohort, there were 1570 (0.40%) cases of AAA over a median 11.3 years of follow-up. Components of the AAA risk score were age (stratified by smoking status), weight (stratified by smoking status), antihypertensive and cholesterol-lowering medication use, height, diastolic blood pressure, baseline cardiovascular disease, and diabetes. In the validation cohort, over 10 years of follow-up, the C-index for the model of the USPSTF guidelines was 0.705 (95% CI, 0.678-0.733). The C-index of the risk score as a continuous variable was 0.856 (95% CI, 0.837-0.878). In the validation cohort, the USPSTF model yielded sensitivity 63.9% and specificity 71.3%. At the 0.25% 10-year risk threshold, the risk score yielded sensitivity 82.1% and specificity 70.7% while also improving the net reclassification index compared with the USPSTF model +0.176 (95% CI, 0.120-0.232). A combined model, whereby risk scoring was combined with the USPSTF model, also improved prediction compared with USPSTF alone (net reclassification index +0.101 [95% CI, 0.055-0.147]). In an asymptomatic general population, a risk score based on patient age, height, weight, and medical history may improve identification of asymptomatic patients at risk for clinical events from AAA. Further development and validation of risk scores to detect asymptomatic AAA are needed.

Association of premature menopause with incident pulmonary hypertension: A cohort study.

Several forms of pulmonary hypertension (PH) disproportionately affect women. Animal and human studies suggest that estradiol exerts mixed effects on the pulmonary vasculature. Whether premature menopause represents a risk factor for PH is unknown. In this cohort study, women in the UK Biobank aged 40-69 years who were postmenopausal and had complete data available on reproductive history were included. Premature menopause, defined as menopause occurring before age 40 years. Postmenopausal women without premature menopause served as the reference group. The primary outcome was incident PH, ascertained by appearance of a qualifying ICD code in the participant's UK Biobank study record. Of 136,715 postmenopausal women included, 5,201 (3.8%) had premature menopause. Participants were followed up for a median of 11.1 (interquartile range 10.5-11.8) years. The primary outcome occurred in 38 women (0.73%) with premature menopause and 409 (0.31%) without. After adjustment for age, race, ever-smoking, body-mass index, systolic blood pressure, antihypertensive medication use, non-high-density lipoprotein cholesterol, cholesterol-lowering medication use, C-reactive protein, prevalent type 2 diabetes, obstructive sleep apnea, heart failure, mitral regurgitation, aortic stenosis, venous thromboembolism, forced vital capacity (FVC), the forced expiratory volume in 1 second-to-FVC ratio, use of menopausal hormone therapy, and hysterectomy status, premature menopause was independently associated with PH (hazard ratio 2.13, 95% CI 1.31-3.23, P<0.001). In analyses of alternate menopausal age thresholds, risk of PH appeared to increase progressively with younger age at menopause (Ptrend <0.001), with 4.8-fold risk in women with menopause before age 30 years (95% CI 1.82-12.74, P = 0.002). Use of menopausal hormone therapy did not modify the association of premature menopause with PH. Premature menopause may represent an independent risk factor for PH in women. Further investigation of the role of sex hormones in PH is needed in animal and human studies to elucidate pathobiology and identify novel therapeutic targets.