Use Of Cholesterol-lowering Medications Research Articles

Abstract MP64: APOL1 Renal Risk Variants Associate With Heart Failure With Preserved Ejection Fraction in African-American Women

Introduction: African origin coding variants in APOL1 , encoding apolipoprotein L1, are strongly associated with various kidney diseases in African Americans, with odds ratio ranging from 7 to 89 for two renal risk allele carriers. APOL1 renal risk genotypes may influence risk for cardiovascular disease and mortality, but findings have been inconsistent. Hypothesis: Given that African-American aging women are at high risk for cardiovascular disease and stroke, we asked whether APOL1 risk genotypes affect these outcomes. Methods: We used data from 11,137 African-American postmenopausal women who participated in the Women’s Health Initiative prospective cohort, followed from enrollment (1993-1998) to 2014. APOL1 genotypes were obtained directly or by imputation from whole exome sequencing data. Adjudicated outcomes were incident coronary heart disease, stroke and subtypes, heart failure and subtypes, and overall and cause-specific mortality obtained from hospital records and death certificates. End-stage renal disease status (ESRD) was obtained from the US Renal Data System. We estimated incident rates for each outcome and used Cox proportional hazard to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of APOL1 high and low risk groups with outcomes. Results: Mean age was 61.7 years. APOL1 high risk carriers (12.3% of participants) had higher prevalence of hypertension, use of cholesterol lowering medication, and reduced estimated glomerular filtration rate (eGFR), defined as <60 mL/min/1.73 m 2 . After 11 years mean follow-up APOL1 high risk subjects had a higher incident rate of ESRD and hospitalized heart failure with preserved ejection fraction (HFpEF) than low risk carriers, but showed no difference in the incident rates of other outcomes. In adjusted models, there were a significant 43% increased hazard of ESRD (95% CI 1.01, 2.02), and a 58% increased hazard of hospitalized HFpEF (95% CI 1.03, 2.41) among high risk compared to low risk APOL1 carriers. In sensitivity analyses restricted to the genome-wide association sample and accounting for population stratification (n=7,797), the associations remained significant for HFpEF. These associations were no longer significant after adjusting for eGFR. Conclusions: We identified novel associations of APOL1 high risk status with hospitalization for HFpEF among postmenopausal women, which are likely mediated by APOL1 -induced chronic kidney disease. We also showed lack of association of APOL1 with incident coronary heart disease, stroke and mortality.

Trends in lipid profiles and descriptive characteristics of U.S. adults with and without diabetes and cholesterol-lowering medication use-National Health and Nutrition Examination Survey, 2003-2012, United States.

BackgroundWith a cholesterol-lowering focus for diabetic adults and in the age of polypharmacy, it is important to understand how lipid profile levels differ among those with and without diabetes.ObjectiveInvestigate the means, differences, and trends in lipid profile measures [TC, total cholesterol; LDL-c, low-density lipoprotein; HDL-c, high-density lipoprotein; and TG, triglycerides] among US adults by diabetes status and cholesterol-lowering medication.MethodsPopulation number and proportion of adults aged ≥21 years with diabetes and taking cholesterol-lowering medication were estimated using data on 10,384 participants from NHANES 2003–2012. Age-standardized means, trends, and differences in lipid profile measures were estimated by diabetes status and cholesterol medication use. For trends and differences, linear regression analysis were used adjusted for age, gender, and race/ethnicity.ResultsAmong diabetic adults, 52% were taking cholesterol-lowering medication compared to the 14% taking cholesterol-lowering medication without diabetes. Although diabetic adults had significantly lower TC and LDL-c levels than non-diabetic adults [% difference (95% confidence interval): TC = -5.2% (-6.8 –-3.5), LDL-c = -8.0% (-10.4 –-5.5)], the percent difference was greater among adults taking cholesterol medication [TC = -8.0% (-10.3 –-5.7); LDL-c = -13.7% (-17.1 –-10.2)] than adults not taking cholesterol medication [TC = -3.5% (-5.2 –-1.6); LDL-c = -4.3% (-7.1 –-1.5)] (interaction p-value: TC = <0.001; LDL-c = <0.001). From 2003–2012, mean TC and HDL-c significantly decreased among diabetic adults taking cholesterol medication [% difference per survey cycle (p-value for linear trend): TC = -2.3% (0.003) and HDL-c = -2.3% (0.033)]. Mean TC, HDL-c, and LDL-c levels did not significantly change from 2003 to 2012 in non-diabetic adults taking cholesterol medication or for adults not taking cholesterol medications.ConclusionsDiabetic adults were more likely to have lower lipid levels, except for triglyceride levels, than non-diabetic adults with profound differences when considering cholesterol medication use, possibly due to the positive effects from clinical diabetes management.

Neurological and Neuropsychiatric Disorders-1The Impact of Cholesterol-lowering Medication Use and Plasma Lipid Levels on Cognitive and Motor Function in Parkinson's Disease

Neurological and Neuropsychiatric Disorders-1The Impact of Cholesterol-lowering Medication Use and Plasma Lipid Levels on Cognitive and Motor Function in Parkinson's Disease

The effect of non-steroidal anti-inflammatory drugs on risk of benign prostatic hyperplasia.

Inflammation may play a role in pathogenesis of benign prostatic hyperplasia (BPH). However, the role of non-steroidal anti-inflammatory drugs (NSAIDs) as BPH risk factor is unclear. The objective of this study was to examine risk of BPH by NSAID use in a population-based cohort. A total of 74 754 Finnish men without previous BPH at baseline in 1996-1999 were linked to national medication reimbursement database for information on physician-prescribed NSAID purchases during 1995-2009. Information on BPH procedures and diagnoses was obtained from national Care Register for Health Care. Cox regression with adjustment for age and use of cholesterol-lowering, antidiabetic and antihypertensive medication, with NSAID use as time-dependent variable was used to analyse the risk of BPH surgery, medication use, and recorded diagnosis. Of the subjects 57 707 men (77.2%) used prescription NSAIDs. The risk of BPH was elevated among NSAID users compared to non-users: HR 2.04, 95% CI 1.97-2.10 for BPH medication use, HR 1.59, 95% CI 1.47-1.71 for recorded diagnosis and HR 1.61, 95% CI 1.49-1.74 for surgery. The risk increase correlated with duration of NSAID usage, less with annual dosage. Nevertheless, the risk increase was observed already at short-term and low-dosage use. NSAID use is associated with an increased risk of BPH. The association is affected by systematic differences by NSAID use as the risk increase was observed already at short-term use. Nevertheless, the association correlated with duration of use, suggesting that NSAID usage or the conditions indicating it may increase BPH risk.

The association between metabolic health, obesity phenotype and the risk of breast cancer.

Beyond the current emphasis on body mass index (BMI), it is unknown whether breast cancer risk differs between metabolically healthy and unhealthy normal weight or overweight/obese women. The Sister Study is a nationwide prospective cohort study. Data came from 50,884 cohort participants aged 35 to 74 years enrolled from 2003 through 2009. Cox proportional hazards models were used to estimate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for breast cancer risk. Metabolic abnormalities considered included: high waist circumference (≥88 cm); elevated blood pressure (≥130/85 mm Hg or antihypertensive medication); previously diagnosed diabetes or antidiabetic drug treatment; and cholesterol-lowering medication use. During follow-up (mean, 6.4 years), 1,388 invasive breast cancers were diagnosed at least 1 year after enrollment. Compared to women with BMI <25 kg/m2 with no metabolic abnormalities (metabolically healthy normal weight phenotype), women with a BMI <25 kg/m2 and ≥1 metabolic abnormality (metabolically unhealthy, normal weight phenotype) had increased risk of postmenopausal breast cancer (HR = 1.26, 95% CI: 1.01-1.56), as did women with a BMI ≥25 kg/m2 and no metabolic abnormalities (metabolically healthy overweight/obese phenotype) (HR = 1.24, 95% CI: 0.99-1.55). Furthermore, risk of postmenopausal breast cancer was consistently elevated in women with normal BMI and central obesity (normal weight central obesity phenotype) regardless of the criterion used to define central obesity, with HR for waist circumference ≥88 cm, waist circumference ≥80 cm, and waist-hip ratio ≥0.85 of 1.58, 95% CI: 1.02-2.46; 1.38, 95% CI: 1.09-1.75; and 1.38, 95% CI: 1.02-1.85, respectively. There was an inverse association between premenopausal breast cancer and metabolically healthy overweight/obese phenotype (HR = 0.71, 95% CI: 0.52-0.97). Our findings suggest that postmenopausal women who are metabolically unhealthy or have central adiposity may be at increased risk for breast cancer despite normal BMI.

Habitual and Recent Sleep Durations: Graded and Interactive Risk for Impaired Glycemic Control in a Biracial Population

BackgroundWe examined how habitual sleep duration interacts with recent sleep (2 nights) to predict morning oral glucose tolerance test results. We hypothesized that short habitual and recent sleep durations would be additive for poor glucose control. MethodsA biracial population of adults (n = 1559) without known diabetes and recruited from the workforce of 2 urban universities was assessed for glycated hemoglobin and underwent oral glucose tolerance testing. We used plasma 2-hour postloading (75 g) measurements. Participants answered sleep questions using 30-minute forced-choice formats. We employed multivariable logistic regression to derive odds ratios. ResultsShorter habitual sleep duration was associated with greater odds ratios of glycated hemoglobin ≥6.0% increasing by 30-minute intervals beginning at <7.0 hours and were more pronounced as durations shortened. Among participants with glycated hemoglobin <6.0% and <7.0 hours of habitual sleep (n = 636), abnormal glucose tolerance (2-hour oral glucose tolerance test ≥140 mg/dL) was significantly associated with a total sleep duration of ≤11 hours the 2 nights preceding oral glucose tolerance testing, but was not associated with longer sleep durations. Results were independent of age, sex, race, body mass index, smoking, history of cardiovascular disease, or use of antihypertensive or cholesterol-lowering medication. Additional analyses implied that longer-than-usual recent sleep durations were protective for abnormal oral glucose tolerance testing. DiscussionShort habitual and recent sleep durations interact in predicting abnormal glucose on oral glucose tolerance testing. Self-reported data are sufficiently sensitive to reflect 30-minute differences in sleep between individuals. Future studies examining other aspects of sleep, such as perceived sleep quality and objectively measured sleep duration and architecture, would be necessary to confirm these findings. ConclusionsShort sleep duration for 2 nights prior to morning oral glucose tolerance testing may elevate glucose levels, this effect being detected among individuals habitually obtaining <7 hours sleep and obtaining ≤11 hours of sleep for 2 nights preceding testing.

Association of Paraoxonase 1 Polymorphism and Serum 25-Hydroxyvitamin D with the Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have significantly increased cardiovascular (CV) morbidity and mortality that are not accounted for by traditional risk factors alone. Paraoxonase 1 (PON1) and 25-hydroxyvitamin D have been shown to be involved in the pathogenesis of CV diseases. Objective: This study aimed to investigate PON1 gene polymorphism and serum 25-hydroxyvitamin D concentrations in RA patients, and to determine their association with CV risk in RA. Serum samples from 46 RA patients and 45 healthy controls were tested for PON1 R192Q genotypes and serum vitamin D concentrations. The cardiovascular risks were assessed by Q-risk. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease activity status were also assessed. PON1 polymorphism and low serum 25-hydroxyvitamin D were significantly associated with increased CV risk (p < 0.05). Compared to patients with either the PON1 QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased CV risk on multivariate analysis, controlling for traditional CV risk factors, C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (p < 0.05). There was a relationship of the genetic determinants of paraoxonase 1 (PON1 192) and serum 25-hydroxyvitamin D to CV risk in RA patients. Paired measurement of paraoxonase 1 genotype and serum 25-hydroxyvitamin D can be used as biomarkers of CV risk in RA patients.

Association of tobacco use and cessation with coronary atherosclerosis

Background and aimsThe impact of tobacco use and cessation on atherogenesis remains unclear. We aimed to study the association of tobacco use and prior cessation with the presence, extent and severity of atherosclerosis on coronary computed tomographic angiography (CTA). MethodsWe examined 1798 consecutive symptomatic patients without known coronary artery disease (CAD) referred for CTA, stratified by smoking status (never, current [within 30 days], or former [>30 days before CTA]). Plaque severity (none, <50%, ≥50% stenosis), composition (non-calcified [NCP], partially calcified [PCP], or calcified plaque [CP]), and segment involvement score (SIS) were visually graded. Multivariate analysis was performed, adjusting for CAD risk factors and cholesterol lowering medication use. ResultsThe median age of patients was 50 years [IQR:42–58] (61% male), with 74% never smokers, 12% current smokers, and 14% former smokers (median quit duration = 12 years [IQR:3–26]). Smoking exposure in former versus current smokers was 11 [IQR:5–25] and 10 [IQR:2–20] pack-years, respectively (p = 0.01). Compared to never smokers, current smokers demonstrated an increased odds ratio of all plaque types (adjusted OR: any NCP = 1.55 [95% CI 1.04–2.32], p = 0.03; any PCP = 1.61 [1.10–2.37], p = 0.02; any CP = 1.93 [1.32–2.81], p = 0.001), non-obstructive CAD (aOR = 1.47 [1.04, 2.07], p = 0.03), obstructive CAD (aOR = 1.81 [1.01–3.24], p = 0.047), and SIS > 4 (aOR = 1.60 [1.04–2.46], p = 0.03). Compared to current smoking, prior smoking cessation (≥12 years) was associated with a decreased odds ratio of any NCP (aOR = 0.42 [0.19–0.90], p = 0.03), CP (aOR = 0.43 [0.22–0.84], p = 0.02), and obstructive CAD (aOR = 0.40, [0.15–0.98], p = 0.048). ConclusionsCurrent smoking is independently associated with the presence and extent of coronary plaque, and a higher risk of non-obstructive and obstructive CAD compared to never smoking. Prior smoking cessation correlated with improvements in CTA-identified plaque measures.

Does the ACAAs Medicaid Expansion Improve Health?

We estimate the effects of the ACA’s Medicaid expansion on health outcomes with a difference-in-differences approach, using restricted geotagged NHANES data from 2007 to 2014. Our results show that the partial Medicaid expansion in 2014 is significantly associated with a decrease of 8.465 mg / dL (4.3%) in total cholesterol and decrease of 5.569 mmHg in systolic blood pressure (4.7%). These are both likely the result of an increase in the use of cholesterol lowering medications, which can affect both of these measures and there is no corresponding increase in blood pressure prescription. Contrastingly, we find no statistically significant effects for diabetes prescriptions or measures.

What the Latest Evidence Tells Us About Fat and Cardiovascular Health.

Diabetes has long been considered a risk equivalent to coronary heart disease (CHD) (1,2). The first report of the National Cholesterol Education Program, released in 1988, encouraged therapeutic lifestyle changes (nutrition, weight management, and physical activity) as first-line therapy for treating high blood cholesterol. Included in these recommendations was advice to eat a low-fat, low-cholesterol diet (3). This article presents a summary of the current evidence regarding dietary fat as it relates to diabetes and heart health, including the shift to thinking about type (or quality) of fat, rather than focusing as much on quantity. In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) released new guidelines for the treatment of blood cholesterol. These guidelines recommended a significant shift from aiming for specific LDL cholesterol goals to considering the overall risk level for having both a heart attack and stroke (4). The guidelines also identified four major groups of patients for whom statin medications are indicated because they have the greatest likelihood of preventing stroke and heart attacks, including individuals with diabetes who are 40–75 years of age. Although treating based on risk now trumps treating to LDL targets, the ACC/AHA re-emphasized that lifestyle modification remains a crucial component of cardiovascular disease (CVD) risk reduction, both before and with the use of cholesterol-lowering medications (5). As of 2015, the American Diabetes Association (ADA) Standards of Medical Care in Diabetes have aligned with the ACC/AHA guidelines and recommend statin therapy for all adults with diabetes who have CVD risk factors or overt CVD, unless contraindicated or not tolerated (6). Current diabetes nutrition recommendations center around individualized eating patterns that focus on a nutrient-rich, whole-foods approach (in appropriate portions) to attain individual blood glucose, blood pressure, blood lipid, and body weight goals, as well …

Prevalence of Intracranial Atherosclerotic Stenosis Using High-Resolution Magnetic Resonance Angiography in the General Population: The Atherosclerosis Risk in Communities Study.

Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke, but little is known about its epidemiology. We studied the prevalence of ICAS and its association with vascular risk factors using high-resolution magnetic resonance angiography in a US cardiovascular cohort. The Atherosclerosis Risk in Communities (ARIC) study recruited participants from 4 US communities from 1987 to 1989. Using stratified sampling, we selected 1980 participants from visit 5 (2011-2013) for high-resolution 3T-magnetic resonance angiography. All images were analyzed in a centralized laboratory, and ICAS was graded as: no stenosis, <50% stenosis, 50% to 69% stenosis, 70% to 99% stenosis, and complete occlusion. We calculated per-vessel and per-person prevalence of ICAS (weighted for n=6538 visit 5 participants) and also estimated the US prevalence. We used multivariable logistic regression to identify variables independently associated with ICAS. Subjects who had an adequate magnetic resonance angiography (n=1765) were aged 67 to 90 years, 41% were men, 70% were white, and 29% were black. ICAS was prevalent in 31% of participants and 9% had ICAS ≥50%. Estimated US prevalence of ICAS ≥50% for 65 to 90 years old was 8% for whites and 12% for blacks. Older age, black race, higher systolic blood pressure, and higher low-density lipoprotein cholesterol levels were associated with increased odds of ICAS, whereas higher levels of high-density lipoprotein cholesterol and use of cholesterol-lowering medications were associated with decreased odds of ICAS. Body mass index and smoking were not associated with ICAS. The prevalence of ICAS in older adults is high, and it could be a target for primary prevention of stroke and dementia in this population.

Abstract PD1-03: Cholesterol, cholesterol lowering medication use, and breast cancer outcomes in the BIG 1-98 study

Abstract Background: Cholesterol lowering medications (CLM)—statins in particular—may exert anti-cancer effects. A proposed mechanism involves attenuated signaling through the estrogen receptor by the cholesterol metabolite, 27-hydroxycholesterol, which correlates with systemic total cholesterol. Assessment of cholesterol levels and use of cholesterol-lowering medications among breast cancer patients receiving endocrine treatment may enrich our understanding of factors affecting endocrine therapy effectiveness and the role of statins and cholesterol in cancer survival. Aim: To investigate the prognostic effect of baseline cholesterol level and baseline CLM use, and to study the effect on outcome of concurrent use of CLM and endocrine therapy in the BIG 1-98 study. Design and Methods: The BIG 1-98 study enrolled 8,010 postmenopausal women with early-stage, estrogen receptor-positive invasive breast cancer from 1998-2003. Participants were randomized to five years of tamoxifen, letrozole, or their sequence. Cholesterol levels and use of CLM were assessed at baseline and every six months up to 5.5 years. Multivariable prognostic models of baseline cholesterol or baseline CLM use were adjusted for patient- and tumor characteristics and treatment regimen. Prognostic analyses of baseline cholesterol were restricted to women not taking CLM at baseline. Marginal structural modeling was used to investigate the relationship between initiation of CLM during endocrine therapy and outcome. Median follow-up was approximately 8 years. Endpoints were: disease-free survival (DFS), breast cancer-free interval (BCFI), and distant recurrence-free interval (DRFI). Results: Among 7,963 women who received at least one dose of endocrine therapy, 637 reported use of CLM at baseline, including statins (n=490) and non-statins (n=147). Compared with non-users, women on CLM at baseline were older, more often had a history of diabetes, were more likely to use hormone replacement therapy, and were more often diagnosed with smaller tumors or node-negative disease. During follow-up, 2,005 DFS-events, 1,303 BCFI-events and 1,004 DRFI-events were reported. Among non-users of CLM at baseline, baseline cholesterol levels showed a significant U-shaped association with BCFI and DRFI when grouped according to the quartiles of the distribution; however, these results were not maintained using cardiovascular risk-based cholesterol cut points. Prognostic models also suggested that use of any CLM at baseline was associated with better DFS compared with non-use (HRadj=0.82, 95% CI: 0.68, 0.99); similar, but non-significant associations were seen for BCFI (HRadj=0.83, 95% CI: 0.65, 1.06) and DRFI (HRadj=0.81, 95% CI: 0.61, 1.09). Results from the marginal structural modeling showed no differences in outcomes for women who initiated CLM during endocrine therapy compared with those who did not. Conclusions: In the BIG 1-98 study investigating the use of tamoxifen, letrozole or their sequence as endocrine therapy in the adjuvant setting, use of cholesterol-lowering therapy at baseline was associated with beneficial tumor characteristics. The effects on clinical outcome need further investigation. Citation Format: Borgquist S, Giobbie-Hurder A, Ahern T, Garber JE, Colleoni M, Láng I, Debled M, Ejlertsen B, Coates AS, Goldhirsch A, Price KN, Gelber RD, Regan MM, Thürlimann B. Cholesterol, cholesterol lowering medication use, and breast cancer outcomes in the BIG 1-98 study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD1-03.

Gender Difference in the Epidemiological Association between Metabolic Syndrome and Olfactory Dysfunction: The Korea National Health and Nutrition Examination Survey.

Metabolic syndrome (MetS) is associated with a higher risk of morbidity and/or mortality for various chronic diseases. The aim of this study was to investigate the relationships of MetS and its components with olfactory dysfunction in a representative Korean population. We analyzed the data from the Korean National Health and Nutrition Examination Survey (2008–2010). A total of 11,609 adults who underwent otolaryngological examination were evaluated. The olfactory function was classified as normosmia or hyposmia by a self-report questionnaire according to the sense problems of smell during the past 3 months. MetS was diagnosed if a participant had at least three of the following: (1) WC ≥90 cm in men and ≥80 cm in women; (2) fasting blood sugar ≥ 100 mg/dL or medication use for elevated glucose; (3) fasting triglyceride ≥ 150 mg/dL or cholesterol-lowering medication use; (4) HDL-cholesterol <40 mg/dL in men and <50 mg/dL in women or cholesterol-lowering medication use; and (5) SBP ≥ 130 mmHg and/or DBP ≥ 85 mmHg or antihypertensive drug use for patients with a history of hypertension. The prevalence of olfactory dysfunction in the study population was 6.3%. The prevalence of olfactory dysfunction was significantly higher in older people with MetS than in those without MetS in both sexes (male, 42.0 ± 3.4% vs. 34.7 ± 0.9%, p = 0.0354; female, 46.2 ± 2.8% vs. 37.8 ± 0.8%, p = 0.0026). However, elevated waist circumference, elevated fasting glucose, elevated triglycerides, reduced HDL cholesterol, elevated blood pressure, severe stress, depressed mood, and suicidal ideation were significantly associated with olfactory dysfunction only in women. After controlling for confounders, olfactory dysfunction was significantly associated with MetS (odds ratio, 1.352; 95% confidence interval, 1.005–1.820) only in women. MetS are associated with olfactory dysfunction only in Korean women.

Factor XI Deficiency Protects Against Atherogenesis in Apolipoprotein E/Factor XI Double Knockout Mice.

Atherosclerosis and atherothrombosis are still major causes of mortality in the Western world, even after the widespread use of cholesterol-lowering medications. Recently, an association between local thrombin generation and atherosclerotic burden has been reported. Here, we studied the role of factor XI (FXI) deficiency in the process of atherosclerosis in mice. Apolipoprotein E/FXI double knockout mice, created for the first time in our laboratory. There was no difference in cholesterol levels or lipoprotein profiles between apolipoprotein E knockout and double knockout mice. Nevertheless, in 24-week-old double knockout mice, the atherosclerotic lesion area in the aortic sinus was reduced by 32% (P=0.004) in comparison with apolipoprotein E knockout mice. In 42-week-old double knockout mice, FXI deficiency inhibited atherosclerosis progression significantly in the aortic sinus (25% reduction, P=0.024) and in the aortic arch (49% reduction, P=0.028), with a prominent reduction of macrophage infiltration in the atherosclerotic lesions. FXI deprivation was shown to slow down atherogenesis in mice. The results suggest that the development of atherosclerosis can be prevented by targeting FXI.

Use of Cholesterol-Lowering Medications of Patients with Myocardial Infarction from 2007-2015 in Cardiology Clinic to “Mother Teresa” University Hospital in Albania

Background: Coronary Heart Disease (CHD) remains the leading cause of morbidity and mortality in Albania. According to Institute of Statistics of Albania (ISA), CHD remains in the 5 first places caused mortality and morbidity in our country. Currently, all the protocol treatments to Mother Teresa University Hospital (MTUH) are focused on low-density lipoprotein cholesterol (LDL-C) as the primary target for risk reduction therapy, followed by triglycerides (TG) and high-density lipoprotein cholesterol (HDL). Our clinicians recommend that the intensity and target goals of LDL-C-lowering therapy should be adjusted to individual treatment. The choice of a specific drug from anti hypercholesterolemia class depends on several factors which need to be evaluated better from our health providers. Methods and Findings: Data was collected between 2007 to 2015 at Mother Teresa University Hospital (MTUH), Intensive Care Unit in Cardiology Clinic. 700 patients were treated with statins as follows: Fluvastain 40 mg and 80 mg, Atorvastatin 10 mg and 20 mg, Simvastatin and Rosuvastatin 20 mg. Statins are increased significantly during the years compared with fibrates. Their use grew from 87% of all statin types to 95% in 2015, with different types from fluvastatin in 2007 to atorvastatin being the leading medication in 2015. Coronary Heart Disease, especially Myocardium Infarct, were studied as diseases when meanly the hypolipidic drugs were usually used in medical protocol treatment. Statins and fibrates were the therapy target to be studied when statin dominated the patients’ treatment and fibrates were used in limited quantity. Atorvastatin is now dominating the market, while fluvastatin was on the first statin therapy for several years in the past. Fibrate were used in the modest quantities in value from 2% to 1.5% in years 2007 to 2015. The use of statins in moderate-risk and high-risk patients showed continued growth subsequently, but stable with dosage of atorvastatin 20 mg. Lower statin dosage used was independently associated for all patients, young patients had used high dosage of statins and fluvastatin respectively 40 mg and 80 mg. The missing high dosage of atorvastatin was notable. The values of LDL were improved but not in the level of efficacy of treatment. Conclusion: Statin therapy becomes more selected compared with fibrate. Atorvastatin 20 mg remains the most important stain used in our clinic, but low dosage remains still a problem. The expected level of LDL-C is the target for the practitioners. More aggressive statins such as rosuvastatin start to be present in our clinic, but it is less used by the patients. Meanwhile the lifestyle, exercises, balance diet, smoking cessation are parts of the patients’ files. The side effects are minors and the medication process has continued.

Prevalence of Cholesterol Treatment Eligibility and Medication Use Among Adults--United States, 2005-2012.

A high blood level of low-density lipoprotein cholesterol (LDL-C) remains a major risk factor for atherosclerotic cardiovascular disease (ASCVD), although data from 2005 through 2012 has shown a decline in high cholesterol (total and LDL cholesterol) along with an increase in the use of cholesterol-lowering medications. The most recent national guidelines (published in 2013) from the American College of Cardiology and the American Heart Association (ACC/AHA) expand previous recommendations for reducing cholesterol to include lifestyle modifications and medication use as part of complete cholesterol management and to lower risk for ASCVD. Because changes in cholesterol treatment guidelines might magnify existing disparities in care and medication use, it is important to describe persons currently eligible for treatment and medication use, particularly as more providers implement the 2013 ACC/AHA guidelines. To understand baseline estimates of U.S. adults on or eligible for cholesterol treatment, as well as to identify sex and racial/ethnic disparities, CDC analyzed data from the 2005-2012 National Health and Nutrition Examination Surveys (NHANES). Because the 2013 ACC/AHA guidelines focus on initiation or continuation of cholesterol treatment, adults meeting the guidelines' eligibility criteria as well as adults who were currently taking cholesterol-lowering medication were assessed as a group. Overall, 36.7% of U.S. adults or 78.1 million persons aged ≥21 years were on or eligible for cholesterol treatment. Within this group, 55.5% were currently taking cholesterol-lowering medication, and 46.6% reported making lifestyle modifications, such as exercising, dietary changes, or controlling their weight, to lower cholesterol; 37.1% reported making lifestyle modifications and taking medication, and 35.5% reported doing neither. Among adults on or eligible for cholesterol-lowering medication, the proportion taking cholesterol-lowering medication was higher for women than men and for non-Hispanic whites (whites) than Mexican-Americans and non-Hispanic blacks (blacks). Further efforts by clinicians and public health practitioners are needed to implement complementary and targeted patient education and disease management programs to reduce sex and racial/ethnic disparities among adults eligible for treatment of cholesterol.

The Onion Sign in Neovascular Age-Related Macular Degeneration Represents Cholesterol Crystals

To investigate the frequency, natural evolution, and histologic correlates of layered, hyperreflective, subretinal pigment epithelium (sub-RPE) lines, known as the onion sign, in neovascular age-related macular degeneration (AMD). Retrospective observational cohort study and experimental laboratory study. Two hundred thirty eyes of 150 consecutive patients with neovascular AMD and 40 human donor eyes with histopathologic diagnosis of neovascular AMD. Spectral-domain optical coherence tomography (SD OCT), near-infrared reflectance (NIR), color fundus images, and medical charts were reviewed. Donor eyes underwent multimodal ex vivo imaging, including SD OCT, before processing for high-resolution histologic analysis. Presence of layered, hyperreflective sub-RPE lines, qualitative analysis of their change in appearance over time with SD OCT, histologic correlates of these lines, and associated findings within surrounding tissues. Sixteen of 230 eyes of patients (7.0%) and 2 of 40 donor eyes (5.0%) with neovascular AMD had layered, hyperreflective sub-RPE lines on SD OCT imaging. These appeared as refractile, yellow-gray exudates on color imaging and as hyperreflective lesions on NIR. In all 16 patient eyes, the onion sign persisted in follow-up for up to 5 years, with fluctuations in the abundance of lines and association with intraretinal hyperreflective foci. Patients with the onion sign disproportionately were taking cholesterol-lowering medications (P=0.025). Histologic analysis of 2 donor eyes revealed that the hyperreflective lines correlated with clefts created by extraction of cholesterol crystals during tissue processing. The fluid surrounding the crystals contained lipid, yet was distinct from oily drusen. Intraretinal hyperreflective foci correlated with intraretinal RPE and lipid-filled cells of probable monocytic origin. Persistent and dynamic, the onion sign represents sub-RPE cholesterol crystal precipitation in an aqueous environment. The frequency of the onion sign in neovascular AMD in a referral practice and a pathology archive is 5% to 7%. Associations include use of cholesterol-lowering medication and intraretinal hyperreflective foci attributable to RPE cells and lipid-filled cells of monocyte origin.

Plasma lipid levels and colorectal adenoma risk.

Abnormalities in lipid levels have been associated with colorectal neoplasm risk; however, few studies have adjusted for use of cholesterol-lowering medications. The objective of this study was to determine the association of plasma lipid levels with adenoma risk while accounting for statin medication use. We included 254 subjects with advanced adenoma, 246 with single small adenoma, 179 with multiple small adenoma cases, and 403 control participants in the Tennessee Colorectal Polyp Study who also had plasma lipid measurements performed. Data on the use of statin medications were available for 83.4% of these participants. The association between plasma lipids and adenoma risk was evaluated using logistic regression models. Participants in the highest quartile of HDL cholesterol (range 52-106 mg/dl) had an adjusted odds ratio of 0.49 (95% CI 0.23, 1.07), 0.35 (95% CI 0.13, 0.91), and 0.22 (95% CI 0.09, 0.54) for single small, multiple small, and advanced adenomas compared to the lowest quartile (range 12-34 mg/dl), respectively. Participants with the highest quartile of triglyceride levels (range 178-721 mg/dl) had an adjusted odds ratio of 2.40 (95% CI 1.26, 4.55), 1.67 (95% CI 0.66, 4.23), and 2.79 (95% CI 1.25, 6.23) for single small, multiple small, and advanced adenoma, respectively, compared to the lowest quartile (range 40-84 mg/dl). When restricted to individuals with known statin medication use, adjusting for statin use did not appreciably affect these results. We found a direct association between triglyceride plasma levels and an inverse association between plasma HDL cholesterol levels and adenoma risk. Both effects were not appreciably changed when accounting for the regular use of statin medication.

Risk factors for developing thyroid-associated ophthalmopathy among individuals with Graves disease.

Thyroid-associated ophthalmopathy (TAO) is a common and debilitating manifestation of Graves disease (GD). Presently little is known about factors that may increase the risk of developing TAO among patients with GD. To identify risk factors associated with the development of TAO among individuals with newly diagnosed GD. In this longitudinal cohort study, all beneficiaries 18 years of age or older with newly diagnosed GD who were continuously enrolled in a large nationwide US managed care network and who visited an eye care professional 1 or more times from 2001 to 2009 were identified. International Classification of Diseases, Ninth Revision, Clinical Modification billing codes were used to identify those who developed manifestations of TAO. Multivariable Cox regression was used to determine the hazard of developing TAO among persons with newly diagnosed GD, with adjustment for sociodemographic factors, systemic medical conditions, thyrotropin levels, and medical and surgical interventions for management of hyperthyroidism. Manifestations of TAO measured by hazard ratios (HRs) with 95% CIs. Of 8404 patients with GD who met the inclusion criteria, 740 (8.8%) developed TAO (mean follow-up, 374 days since initial GD diagnosis). After adjustment for potential confounders, surgical thyroidectomy, alone or in combination with medical therapy, was associated with a 74% decreased hazard for TAO (adjusted HR, 0.26 [95% CI, 0.12-0.51]) compared with radioactive iodine therapy alone. Statin use (for ≥60 days in the past year vs <60 days or nonuse) was associated with a 40% decreased hazard (adjusted HR, 0.60 [CI, 0.37-0.93]). No significant association was found for the use of nonstatin cholesterol-lowering medications or cyclooxygenase 2 inhibitors and the development of TAO. If prospective studies can confirm our finding that a thyroidectomy and statin use are associated with substantially reduced hazards for TAO among patients with GD, preventive measures for this burdensome manifestation of GD may become a reality.

Lower risk of Alzheimer's disease mortality with exercise, statin, and fruit intake.

Whether lifestyle affects Alzheimer's disease (AD) risk remains controversial. Test whether exercise, diet, or statins affect AD mortality in 153,536 participants of the National Runners' and Walkers' Health Studies. Hazard ratios (HR) and 95% confidence intervals (95% CI) were obtained from Cox proportional hazard analyses for AD mortality versus baseline metabolic equivalent (MET) hours/d of exercise energy expenditure (1 MET equals approximately 1 km run), statin use, and fruit intake when adjusted for age, race, gender, education, and exercise mode. The National Death Index identified 175 subjects who died with AD listed as an underlying (n = 116) or contributing (n = 59) cause of death during 11.6-year average mortality surveillance. Relative to exercising <1.07 MET-hours/d, AD mortality was 6.0% lower for 1.07 to 1.8 MET-hours/d (HR: 0.94, 95% CI: 0.59 to 1.46, p = 0.79), 24.8% lower for 1.8 to 3.6 MET-hours/d (HR: 0.75, 95% CI: 0.50 to 1.13, p = 0.17), and 40.1% lower for ≥3.6 MET-hours/d (HR: 0.60, 95% CI: 0.37 to 0.97, p = 0.04). Relative to non-use, statin use was associated with 61% lower AD mortality (HR: 0.39, 95% CI: 0.15 to 0.82, p = 0.01), whereas use of other cholesterol-lowering medications was not (HR: 0.78, 95% CI: 0.40 to 1.38, p = 0.42). Relative to <1 piece of fruit/day, consuming 2 to 3 pieces daily was associated with 39.7% lower AD mortality (HR: 0.60, 95% CI: 0.39 to 0.91, p = 0.02) and ≥3 pieces/day with 60.7% lower AD mortality (HR: 0.39, 95% CI: 0.22 to 0.67, p = 0.0004). Exercise, statin, and fruit intake were associated with lower risk for AD mortality.