ABSTRACT
BACKGROUND: Many hyperlipidemic patients prescribed ß-hydroxy-ß-methylglutaryl coenzyme A reductase inhibitors (statins) are unable or unwilling to take them. A hedonically acceptable snack-based solution formulated from cholesterol-lowering food ingredients could represent a therapeutic alternative but has not been tested in this population. OBJECTIVES: To evaluate the effect of snacks containing a compendium of functional bioactives on fasting LDL cholesterol in statin candidates unwilling to use or intolerant to ≥1 statin drug. Secondary outcomes included changes in circulating total cholesterol (TC), triglycerides, HDL cholesterol, fasting glucose, insulin, and high-sensitivity C-reactive protein concentrations, as well as effects of single-nucleotide polymorphisms (SNPs) on outcome. METHODS: This multicenter, randomized, double-blind, free-living crossover study was composed of 2 regimented phases of 4 wk each, separated by a 4-wk washout. Eighteen men and 36 women, with a mean ± SD age of 49 ± 12 y and mean ± SD LDL cholesterol of 131 ± 32.1 mg/dL, were instructed to ingest a variety of ready-to-eat snacks twice daily as a substitute for something they were consuming already. Other behavior changes were actively discouraged. Treatment products provided ≥5 g fiber, 1000 mg ω-3 (n-3) fatty acids, 1000 mg phytosterols, and 1800 µmol antioxidants per serving. Control products were calorie-matched like-items drawn from the general grocery marketplace. Serum lipids were measured at baseline and the end of each phase and compared using the ANOVA model. Compliance to study foods was confirmed by serum 18:3n-3 concentration assessment. RESULTS: Comparing intervention phase endpoints, LDL cholesterol was reduced a mean ± SD of 8.80 ± 1.69% (P < 0.0001), and TC was reduced a mean ± SD of 5.08 ± 1.12% (P < 0.0001) by treatment foods compared with control foods, whereas effects on other analytes did not differ between treatments. SNPs were not significantly related to outcomes (P ≥ 0.230). Compliance with study foods was 95%. CONCLUSIONS: Consumption of hedonically acceptable snacks containing a compendium of cholesterol-lowering bioactive compounds can rapidly and meaningfully reduce LDL cholesterol in adult patients unable or unwilling to take statin drugs. This trial was registered at clinicaltrials.gov as NCT02341924.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Adult , Cholesterol, HDL , Cholesterol, LDL , Cross-Over Studies , Double-Blind Method , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , NutrientsABSTRACT
PURPOSE OF REVIEW: The purpose of this review article is to summarize the preclinical and clinical evidence supporting the notion of clonal hematopoiesis of indeterminate potential (CHIP), highlight current knowledge gap, and provide future directions. RECENT FINDINGS: Epidemiological studies show that advanced age is a major risk factor for the development of cardiovascular disease (CVD) and cancer, the two leading causes of morbidity and mortality worldwide. While the negative effect of aging on CVD is a reflection of cumulative exposure to various established traditional CVD risk factors, genetic sequencing of whole blood-derived DNA recently revealed that clonal mutations in myeloid stem cells are associated with higher risks of cardiovascular events and hematopoietic malignancies. The clinical repercussions of this biological state, termed CHIP, are increasingly appreciated. Historically, CHIP has been associated with an increased risk of hematological malignancies. However, new research is showing that CHIP is also associated with an increased risk of several cardiac-related conditions, including atherosclerosis, myocardial infarction, aortic valve stenosis, and congestive heart failure. CHIP is increasingly being appreciated worldwide as a CVD risk factor, and further studies are needed to better understand the complex relationship between these two disorders.
Subject(s)
Cardiovascular Diseases/genetics , Clonal Hematopoiesis , Age Factors , Hematologic Neoplasms/genetics , Humans , Mutation , Risk FactorsABSTRACT
BACKGROUND: Guidelines endorse educating patients to self-manage atrial fibrillation (AF) to mitigate AF-related adverse events contributing to personal and societal burden. Published interventions to improve patients' knowledge about AF and self-management are emerging, but evaluations of interventions are limited by lack of a psychometrically sound instrument to measure learning outcomes. OBJECTIVE: We report results of initial psychometric testing of the Knowledge about Atrial Fibrillation and Self-Management (KAFSM) survey. METHODS: Participants (N = 383), from midwest and southeast medical centers, completed the KAFSM survey. Content validity was evaluated by expert review. Construct validity was evaluated using the Pearson correlation procedure for convergent validity with the Knowledge about Atrial Fibrillation test and independent t test for known groups. Factor analysis using principal axis factoring was performed with a tetrachoric matrix. The Kuder-Richardson procedure was used to determine internal consistency reliability. RESULTS: A content validity index of 0.86 resulted from expert review. A positive (r = 0.60) correlation between the KAFSM survey and Knowledge about Atrial Fibrillation test demonstrated convergent validity. Higher KAFSM scores (difference, 3.28; t = 6.44, P < .001) observed in participants who underwent AF ablation compared with those with an AF diagnosis of less than or equal to 6 months supported known groups validity. Factor analysis revealed a single-factor structure explaining 35% of the variance. The Kuder-Richardson coefficient was 0.86. CONCLUSIONS: The KAFSM survey demonstrates content and construct validity and internal consistency reliability. Implementation of the KAFSM in the clinical setting will permit evaluation of the feasibility of its use and value to assess learning outcomes of AF education.
Subject(s)
Atrial Fibrillation/psychology , Self Report/standards , Self-Management/methods , Atrial Fibrillation/diagnosis , Atrial Fibrillation/therapy , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Psychometrics/instrumentation , Quality of Life , Reproducibility of Results , Surveys and Questionnaires/standardsABSTRACT
DESCRIPTION: Calcium is the dominant mineral present in bone and a shortfall nutrient in the American diet. Supplements have been recommended for persons who do not consume adequate calcium from their diet as a standard strategy for the prevention of osteoporosis and related fractures. Whether calcium with or without vitamin D supplementation is beneficial or detrimental to vascular health is not known. METHODS: The National Osteoporosis Foundation and American Society for Preventive Cardiology convened an expert panel to evaluate the effects of dietary and supplemental calcium on cardiovascular disease based on the existing peer-reviewed scientific literature. The panel considered the findings of the accompanying updated evidence report provided by an independent evidence review team at Tufts University. RECOMMENDATION: The National Osteoporosis Foundation and American Society for Preventive Cardiology adopt the position that there is moderate-quality evidence (B level) that calcium with or without vitamin D intake from food or supplements has no relationship (beneficial or harmful) to the risk for cardiovascular and cerebrovascular disease, mortality, or all-cause mortality in generally healthy adults at this time. In light of the evidence available to date, calcium intake from food and supplements that does not exceed the tolerable upper level of intake (defined by the National Academy of Medicine as 2000 to 2500 mg/d) should be considered safe from a cardiovascular standpoint.
Subject(s)
Calcium, Dietary/adverse effects , Cardiovascular Diseases/epidemiology , Dietary Supplements/adverse effects , Vitamin D/adverse effects , Adult , Calcium, Dietary/administration & dosage , Cardiovascular Diseases/etiology , Humans , Risk Factors , Vitamin D/administration & dosageABSTRACT
PURPOSE OF REVIEW: Cholesterol management in the current era is discussed. Aggressive reduction of low density lipoprotein (LDL) cholesterol plays a key role in primary and secondary prevention of heart disease. Statins are the recommended first-line therapy in patients with hyperlipidemia; however, additional complementary approaches are frequently needed for patients who fail to reach their target LDL. RECENT FINDINGS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs that provide dramatic lowering of LDL and promise outcome benefit. Despite great enthusiasm about their cardiovascular benefit, concerns have been raised regarding their cost and added value to the healthcare system. Although cost-effectiveness studies have yielded inconclusive results, analyses suggest that the current cost of PCSK9 inhibitors is disproportionately high and must be significantly reduced to add positive net benefit to healthcare system. PCSK9 inhibitors significantly lower LDL cholesterol. Further outcome data and cost-effectiveness analyses are needed to overcome the current barriers with PCSK9 inhibitors that patients, physicians, and payers face.
Subject(s)
Cholesterol, LDL/blood , Enzyme Inhibitors/therapeutic use , Heart Diseases/prevention & control , PCSK9 Inhibitors , Enzyme Inhibitors/economics , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/drug therapy , Primary Prevention , Secondary PreventionABSTRACT
High-fat, low carb dieting, also known as the "ketogenic diet," has increased in popularity as a rapid weight-loss tool. Previous studies describe a modest elevation in cholesterol in the average keto-diet participant without specific cardiovascular impact. We hypothesize that patients with a genetic predisposition to cholesterol metabolism dysregulation may have a disproportionate elevation in cholesterol in response to ketogenic dieting.
ABSTRACT
Background There is a scarcity of validated rapid dietary screening tools for patient use in the clinical setting to improve health and reduce cardiovascular risk. The Healthy Eating Index (HEI) 2015 measures compliance with the 2015 to 2020 Dietary Guidelines for Americans but requires completion of an extensive diet assessment to compute, which is time consuming and impractical. The authors hypothesize that a 19-item dietary survey assessing consumption of common food groups known to affect health will be correlated with the HEI-2015 assessed by a validated food frequency questionnaire and can be further reduced without affecting validity. Methods and Results A 19-item Eating Assessment Tool (EAT) of common food groups was created through literature review and expert consensus. A cross-sectional survey was then conducted in adult participants from a preventive cardiology clinic or cardiac rehabilitation and in healthy volunteers (n=661, mean age, 36 years; 76% women). Participants completed an online 156-item food frequency questionnaire, which was used to calculate the HEI score using standard methods. The association between each EAT question and HEI group was analyzed by Kruskal-Wallis test. Linear regression models were subsequently used to identify univariable and multivariable predictors for HEI score for further reduction in the number of items. The final 9-item model of Mini-EAT was validated by 5-fold cross validation. The 19-item EAT had a strong correlation with the HEI score (r=0.73) and was subsequently reduced to the 9 items independently predictive of the HEI score: fruits, vegetables, whole grains, refined grains, fish or seafood, legumes/nuts/seeds, low-fat dairy, high-fat dairy, and sweets consumption, without affecting the predictive ability of the tool (r=0.71). Conclusions Mini-EAT is a 9-item validated brief dietary screener that correlates well with a comprehensive food frequency questionnaire. Future studies to test the Mini-EAT's validity in diverse populations and for development of clinical decision support systems to capture changes over time are needed.
Subject(s)
Diet , Vegetables , Animals , Cross-Sectional Studies , Fruit , Surveys and QuestionnairesABSTRACT
BACKGROUND: Heart Failure (HF) is a primary diagnosis for hospital admission from the Emergency Department (ED), although not all patients require hospitalization. The Emergency Heart Failure Mortality Risk Grade (EHMRG) estimates 7-day mortality in patients with acute HF in ED settings, but further validation is needed in the United States (US). OBJECTIVES: To validate EHMRG scores by risk-stratifying patients with acute HF in a large tertiary healthcare center in the US and analyze outcome measures to determine if EHMRG risk scores safely identify low-risk groups that may be discharged or managed in ED observation units (EDOUs). METHODS: A retrospective cohort analysis of 304 patients with acute HF presenting to an ED at a large, tertiary healthcare center was completed. EHMRG scores were calculated to stratify patients according to published thresholds. Mortality and major adverse cardiac event (MACE) rates were analyzed. RESULTS: No deaths occurred in very low and low-risk EHMRG groups at 7 days post discharge. 30-day mortality was significantly less in the lower risk groups (3.1%) when compared to all other patients (11.1%). MACE rates at 30 days in the very low risk group (15%) were significantly less when compared to all other patients (31.3%). Hospitalizations occurred in 23.4% of patients in lower risk groups. CONCLUSIONS: ED risk stratification with EHMRG differentiates high-risk patients requiring hospitalization from lower risk patients who can be safely managed in alternative settings with good outcomes. Data supports improved pathways for patients with acute HF during a time of high hospital volumes.
Subject(s)
Heart Failure , Patient Discharge , Humans , United States/epidemiology , Retrospective Studies , Emergency Service, Hospital , Aftercare , Heart Failure/diagnosis , Hospitalization , Risk AssessmentABSTRACT
PURPOSE: Innovative methods for delivering cardiac rehabilitation (CR) that provide strategies to circumvent the mounting barriers to traditional CR have the potential to widen access to a well-established secondary prevention strategy. Our study assesses the feasibility and acceptability of a novel virtual world-based CR (VWCR) program, Destination Rehab , as an extension of a conventional center-based CR program. METHODS: Adult cardiac patients hospitalized at Mayo Clinic hospitals with a diagnosis for CR and ≥1 modifiable, lifestyle risk factor target-sedentary lifestyle (<3 hr physical activity/wk), unhealthy diet (<5 servings fruits and vegetables/d), or current smoking (>1 yr)-were recruited. Patients participated in an 8-wk health education program using a virtual world (VW) platform from a prior proof-of-concept study and a post-intervention focus group. Primary outcome measures included feasibility and acceptability. Secondary outcome measures included changes from baseline to post-intervention in cardiovascular (CV) health behaviors and biometrics, CV health knowledge, and psychosocial factors. RESULTS: Of the 30 enrolled patients (age 59.1 ± 9.7 yr; 50% women), 93% attended ≥1 session and 71% attended ≥75% of sessions. The overall VWCR experience received an 8 rating (scale 0-10) and had high acceptability. Clinically relevant trends were noted in CV health behaviors and biometrics, although not statistically significant. CONCLUSIONS: The VWCR program is a feasible, highly acceptable, and innovative platform to potentially influence health behaviors and CV risk and may increase accessibility to disadvantaged populations with higher CV disease burdens.
Subject(s)
Cardiac Rehabilitation , Adult , Humans , Female , Middle Aged , Aged , Male , Cardiac Rehabilitation/methods , Pilot Projects , Exercise , Life Style , Risk FactorsABSTRACT
BACKGROUND: Innovative restructuring of cardiac rehabilitation (CR) delivery remains critical to reduce barriers and improve access to diverse populations. Destination Cardiac Rehab is a novel virtual world technology-based CR program delivered through the virtual world platform, Second Life, which previously demonstrated high acceptability as an extension of traditional center-based CR. This study aims to evaluate efficacy and adherence of the virtual world-based CR program compared with center-based CR within a community-informed, implementation science framework. METHODS: Using a noninferiority, hybrid type 1 effectiveness-implementation, randomized controlled trial, 150 patients with an eligible cardiovascular event will be recruited from 6 geographically diverse CR centers across the United States. Participants will be randomized 1:1 to either the 12-week Destination Cardiac Rehab or the center-based CR control groups. The primary efficacy outcome is a composite cardiovascular health score based on the American Heart Association Life's Essential 8 at 3 and 6 months. Adherence outcomes include CR session attendance and participation in exercise sessions. A diverse patient/caregiver/stakeholder advisory board was assembled to guide recruitment, implementation, and dissemination plans and to contextualize study findings. The institutional review board-approved randomized controlled trial will enroll and randomize patients to the intervention (or control group) in 3 consecutive waves/year over 3 years. The results will be published at data collection and analyses completion. CONCLUSIONS: The Destination Cardiac Rehab randomized controlled trial tests an innovative and potentially scalable model to enhance CR participation and advance health equity. Our findings will inform the use of effective virtual CR programs to expand equitable access to diverse patient populations. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05897710.
Subject(s)
Cardiac Rehabilitation , Telerehabilitation , Humans , Cardiac Rehabilitation/methods , Exercise , Randomized Controlled Trials as TopicABSTRACT
Acute coronary syndromes (ACS) are precipitated by a rupture of the atherosclerotic plaque, often at the site of T cell and macrophage infiltration. Here, we show that plaque-infiltrating CD4 T cells effectively kill vascular smooth muscle cells (VSMC). VSMCs sensitive to T cell-mediated killing express the death receptor DR5 (TNF-related apoptosis-inducing ligand [TRAIL] receptor 2), and anti-TRAIL and anti-DR5 antibodies block T cell-mediated apoptosis. CD4 T cells that express TRAIL upon stimulation are expanded in patients with ACS and more effectively induce VSMC apoptosis. Adoptive transfer of plaque-derived CD4 T cells into immunodeficient mice that are engrafted with human atherosclerotic plaque results in apoptosis of VSMCs, which was prevented by coadministration of anti-TRAIL antibody. These data identify that the death pathway is triggered by TRAIL-producing CD4 T cells as a direct mechanism of VSMC apoptosis, a process which may lead to plaque destabilization.
Subject(s)
Apoptosis Regulatory Proteins/immunology , Apoptosis , CD4-Positive T-Lymphocytes/immunology , Heart Diseases/pathology , Membrane Glycoproteins/immunology , Myocytes, Smooth Muscle/pathology , Tumor Necrosis Factor-alpha/immunology , Adoptive Transfer , Animals , Carotid Arteries , Cell Line , Cells, Cultured , Heart Diseases/immunology , Humans , Mice , Muscle, Smooth, Vascular/immunology , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/immunology , TNF-Related Apoptosis-Inducing Ligand , Tissue TransplantationABSTRACT
BACKGROUND: Limited data exist on the long-term outcomes of patients who undergo evaluation in a chest pain unit (CPU). METHODS: Our study included patients with chest pain at intermediate risk for acute cardiovascular events enrolled in the CHEER study. The primary outcome included a composite of death, myocardial infarction, acute heart failure, stroke, and out-of-hospital cardiac arrest. The secondary outcome included a composite of cardiovascular death, myocardial infarction, acute heart failure, stroke, revascularization, and unstable angina. Data were obtained through a medical record review. We compared outcomes between groups randomized to the CPU versus admission, those admitted from the CPU versus dismissed home, and those who were admitted versus dismissed home after a cardiac stress test in the emergency department. RESULTS: The final analysis included 407 patients. Median surveillance length was 5.5 years. No differences in the primary outcome or secondary outcome existed between patients randomized to the CPU versus admitted to hospital (21.6% vs 20.2% and 29.9% vs 33.0%, respectively, P > .05 for all comparisons). Patients admitted from the CPU had higher rates of the secondary outcome (adjusted hazard ratio 2.26) than patients dismissed from the CPU. Patients admitted after a cardiac stress test in the CPU had higher rates of the secondary outcome (adjusted hazard ratio 2.42) than patients dismissed from the CPU. CONCLUSIONS: A CPU does not increase long-term adverse outcomes in patients with chest pain at intermediate risk for an acute event.
Subject(s)
Angina, Unstable/epidemiology , Chest Pain/therapy , Coronary Care Units/methods , Myocardial Infarction/epidemiology , Angina, Unstable/complications , Angina, Unstable/physiopathology , Chest Pain/epidemiology , Chest Pain/etiology , Diagnosis, Differential , Disease Progression , Electrocardiography , Female , Follow-Up Studies , Humans , Incidence , Length of Stay , Male , Middle Aged , Minnesota/epidemiology , Myocardial Infarction/complications , Myocardial Infarction/physiopathology , Patient Admission , Prognosis , Survival Rate/trendsABSTRACT
OBJECTIVE: Despite guideline consensus that quality of nutrition affects most modifiable cardiovascular disease risk factors, the implementation of dietary interventions varies considerably in cardiac rehabilitation (CR) programs. The purpose of this review is to highlight the current existing literature and provide recommendations on best practices for nutrition interventions and future research that support secondary prevention outcomes. REVIEW METHODS: The review examines original investigations, systematic reviews, and guidelines regarding nutrition intervention in CR. SUMMARY: Nutrition intervention in CR plays an integral role in the success of patients; however, the literature is limited and standardization of practice is in its infancy. The role of a qualified registered dietician nutritionist, standardization of dietary assessments, individualized and intensive nutrition interventions, and application of specific behavior change techniques are central components in improving diet in CR. This review provides an overview of the evidence-based cardioprotective diets, nutritional interventions and behavioral strategies in CR, and explores areas for best practices and opportunities for innovation in the delivery of nutrition intervention in CR.
Subject(s)
Cardiac Rehabilitation , Diet , Humans , Secondary PreventionABSTRACT
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved in August 2015 as an adjunct to maximally tolerated statin treatment in those with familial hypercholesterolemia (FH). OBJECTIVE: To assess PCSK9 inhibitor utilization patterns and cholesterol control in the high-risk FH population. METHODS: This study was a retrospective analysis of a large administrative database that includes privately insured and Medicare Advantage patients. Individuals with diagnosis codes for FH from October 2016-September 2019 were identified. Differences in PCSK9 inhibitor utilization between various groups were evaluated using multivariable logistic regression. RESULTS: During the study period, 1:371 people enrolled in medical/pharmacy plans had a diagnosis of FH. While 62.5% (n = 33,649) had medication fills for statins (without PCSK9 inhibitors), only 2.0% (n = 1062) had medication fills for PCSK9 inhibitors (with or without other medications). Compared to men, women were more likely to be untreated (OR 1.23, 95% confidence interval (CI):1.18-1.28, p < 0.01) but more likely to be treated with PCSK9 inhibitors (OR 2.18, 95%CI:1.90-2.49, p < 0.01). Compared to those younger than 55 years of age, older individuals were more likely to be treated (OR 1.64, 95%CI:1.56-1.72, p < 0.01) but less likely to be treated with PCSK9 inhibitors (OR 0.40, 95%CI:0.34-0.47, p < 0.01). Lastly, those with household incomes ≥$40,000 were more likely to be treated with PCSK9 inhibitors than those with lower household incomes (OR 1.69, 95%CI:1.41-2.02, p < 0.01). CONCLUSION: PCSK9 inhibitor utilization in FH remains low. Significant differences exist based on demographic factors. Female sex, higher household incomes, and younger age were associated with increased PCSK9 inhibitor utilization.
Subject(s)
Proprotein Convertase 9 , Adult , Cholesterol, LDL , Humans , Hyperlipoproteinemia Type II , Middle Aged , PCSK9 Inhibitors , Retrospective StudiesABSTRACT
Vasculogenic erectile dysfunction has been aptly called the "canary in the coal mine" for cardiovascular disease because it almost always precedes other manifestations of atherosclerotic cardiovascular disease, including myocardial infarction and stroke. It is common, associated with the presence of modifiable cardiovascular risk factors, and impacted by diet and lifestyle choices. This concise review provides an update on the use of dietary and other lifestyle interventions to improve vasculogenic erectile dysfunction and atherosclerotic cardiovascular disease.
Subject(s)
Diet , Impotence, Vasculogenic/therapy , Life Style , Atherosclerosis/complications , Humans , Impotence, Vasculogenic/etiology , MaleSubject(s)
Heart Diseases/complications , Hernia/complications , Pulmonary Artery/physiopathology , Vasoconstriction/physiology , Ventricular Dysfunction, Right/diagnosis , Ventricular Dysfunction, Right/etiology , Blood Pressure/physiology , Heart Diseases/etiology , Hernia/etiology , Humans , Lung Neoplasms/surgery , Male , Mesothelioma/surgery , Mesothelioma, Malignant , Middle Aged , Pneumonectomy/adverse effects , Stroke Volume/physiology , Ventricular Dysfunction, Right/physiopathologyABSTRACT
The purpose of this research is to demonstrate the feasibility of a 2 dimensional (2D) penile ultrasound vibro-elastography (PUVE) technique for measuring the shear wave speed map over an area of regional of interest (ROI) in the penis. In PUVE, a 0.1 s harmonic vibration at a low frequency is generated on the surface of the penis using a handheld vibrator. An ultrasound probe is used to measure the resulting shear wave propagation in the penis. The shear wave speed is analyzed in the ROI of corpus cavernosum from both sides of penis using a 2D wave speed analysis technique. The shear wave speed of the penis is measured at three excitation frequencies of 100 Hz, 150 Hz, and 200 Hz. The viscoelasticity of penis is analyzed based on the wave speed dispersion with frequency. A pilot study was performed in men with ED and/or PD. It is found that both elasticity and viscosity of corpus cavernosa positively correlate with the peak systolic velocity (PSV) from penile ultrasonography. Both elasticity and viscosity of corpus cavernosa negatively correlate with the cardiovascular (CV) risk for patients with ED and/or PD. These results suggest that PUVE may provide a noninvasive and painless technique for assessing patients with ED/PD and their future CV risk. We will further evaluate PUVE in a large cohort of patients with ED/PD.
Subject(s)
Elasticity Imaging Techniques , Penis , Ultrasonography , Humans , Male , Penis/diagnostic imaging , Pilot Projects , ViscosityABSTRACT
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs that provide striking lowering of low-density lipoprotein cholesterol (LDL-C) when added to maximum tolerated therapy in patients with hypercholesterolemia. Ceramides, novel cardiac risk markers, have been associated with increased cardiovascular mortality, independent of traditional cardiovascular risk factors. The Ceramide Risk Score (CRS) predicts the likelihood of adverse cardiovascular events within 1 to 3 years in patients with coronary artery disease. The effect of PCSK9 inhibition on plasma ceramides is not well known. The study examines the effect of PCSK9 inhibitors on plasma ceramides and CRS in patients with clinical indication for this therapy. Retrospective chart review of consecutive patients with hypercholesterolemia on PCSK9 inhibitors was conducted (nâ¯=â¯24; Mayo Clinic 2015 to 2018). Plasma ceramides were measured before the initiation of PCSK9 inhibitors and 2 to 12 months after treatment. CRS was calculated before and after therapy based on individual plasma concentrations of 4 ceramides. Treatment with PCSK9 inhibitors was associated with significant reduction in mean CRS and individual ceramides levels (p <0.0001). CRS significantly improved with PCSK9 therapy. PCSK9 inhibitors significantly decreased LDL-C levels by 63% (p <0.0001). The absolute reduction in CRS did not correlate with the absolute reduction in LDL-C (râ¯=â¯0.31; confidence interval -0.10 to 0.64), indicating that CRS may evaluate a different pathway for risk reduction beyond LDL-C lowering. In conclusion, treatment with PCSK9 inhibitors is associated with significant reduction in CRS and distinct ceramide levels.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Anticholesteremic Agents/therapeutic use , Ceramides/blood , Hypercholesterolemia/drug therapy , PCSK9 Inhibitors , 1-Alkyl-2-acetylglycerophosphocholine Esterase/blood , Aged , Apolipoprotein A-I/blood , Apolipoproteins B/blood , Cholesterol, LDL/blood , Female , Humans , Hypercholesterolemia/blood , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/drug therapy , Lipoprotein(a)/blood , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
Ceramides are bioactive lipids that act as secondary messengers for both intra- and inter-cellular signaling. Elevated plasma concentrations of ceramides are associated with multiple risk factors of atherosclerotic cardiovascular diseases and comorbidities including obesity, insulin resistance and diabetes mellitus. Furthermore, atherosclerotic plaques have been shown to be highly enriched with ceramides. Increases in ceramide content may accelerate atherosclerosis development by promoting LDL infiltration to the endothelium and aggregation within the intima of artery walls. Thus, ceramides appear to play a key role in the development of cardiometabolic disease due to their central location in major metabolic pathways that intersect lipid and glucose metabolism. Recently published data have shown that ceramides are not only of scientific interest but may also have diagnostic value. Their independent prognostic value for future cardiovascular outcomes over and above LDL cholesterol and other traditional risk factors have consistently been shown in numerous clinical studies. Thus, ceramide testing with a mass spectrometer offers a simple, reproducible and cost-effective blood test for risk stratification in atherosclerotic cardiovascular diseases.