In 2016, the American College of Cardiology published the first expert consensus decision pathway (ECDP) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in ...the management of atherosclerotic cardiovascular disease (ASCVD) risk. Since the publication of that document, additional evidence and perspectives have emerged from randomized clinical trials and other sources, particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD. Most notably, the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial and SPIRE-1 and -2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), assessing evolocumab and bococizumab, respectively, have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients. In addition, further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published. Based on results from these important analyses, the ECDP writing committee judged that it would be desirable to provide a focused update to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities. In the following summary table, changes from the 2016 ECDP to the 2017 ECDP Focused Update are highlighted, and a brief rationale is provided. The content of the full document has been changed accordingly, with more extensive and detailed guidance regarding decision making provided both in the text and in the updated algorithms. Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities on statin therapy for secondary prevention. The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C <190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes. Based on feedback and further deliberation, the ECDP writing committee down-graded recommendations regarding bile acid sequestrant use, recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe. For clarification, the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia, based on clinical criteria with and without genetic testing. Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians, unless there was a compelling reason or new evidence, in which case justification is provided.
Subsequent independent guideline groups, including the 2014 Joint British Societies Consensus Recommendations for the Prevention of Cardiovascular Disease (JBS3) (3), the 2014 Veterans' ...Administration/Department of Defense Guidelines on Management of Dyslipidemia (4), and the recent U.S. Preventive Services Task Force draft recommendations (5), have used similar, rigorous approaches to reviewing and synthesizing evidence, resulting in similar treatment recommendations.\n Joseph Butterfield Chair in Pediatrics Sanofi-Aventis None None None None None Scott M. Grundy Content Reviewer--Chair, Update to ACC/AHA Cholesterol Guideline University of Texas Southwestern Medical Center at Dallas--Professor of Internal Medicine None None None None None None James L. Januzzi Content Reviewer--Chair, ACC Task Force on Clinical Expert Consensus Documents Massachusetts General Hospital--Director, Dennis and Marilyn Barry Fellowship in Cardiology Research Cardiology Division; Harvard Medical School--Hutter Family Professor of Medicine Novartislow * Rochelow * None None Amgen (DSMB) None None Joseph J. Saseen Content Reviewer--Cardiovascular Team Council University of Colorado Anschutz Medical Campus --Professor and Vice Chair, Department of Clinical Pharmacy, Professor, Department of Family Medicine None None None None None None Michael D. Shapiro Content Reviewer--Prevention Council Oregon Health & Science University--Associate Professor of Medicine and RadiologyDirector, Cardiac MR CT ProgramCenter for Preventive CardiologyKnight Cardiovascular Institute None None None Amarindagger Amgendagger Isisdagger Sanofidagger Synagevadagger None None Barbara S. Wiggins Content Reviewer--ACC Task Force on Clinical Expert Consensus Documents Medical University of South Carolina--Clinical Pharmacy Specialist Cardiology, Department of Pharmacy Services None None None None None None black square This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review and determined to be relevant to this document.
The mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is ...unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.
Randomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI). Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041).
In this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects.
clinicaltrials.gov Identifier: NCT01342029.
Beyond conventional risk factors for cardiovascular disease, women face an additional burden of sex-specific risk factors. Key stages of a woman's reproductive history may influence or reveal short- ...and long-term cardiometabolic and cardiovascular trajectories. Early and late menarche, polycystic ovary syndrome, infertility, adverse pregnancy outcomes (eg, hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, and intrauterine growth restriction), and absence of breastfeeding are all associated with increased future cardiovascular disease risk. The menopause transition additionally represents a period of accelerated cardiovascular disease risk, with timing (eg, premature menopause), mechanism, and symptoms of menopause, as well as treatment of menopause symptoms, each contributing to this risk. Differences in conventional cardiovascular disease risk factors appear to explain some, but not all, of the observed associations between reproductive history and later-life cardiovascular disease; further research is needed to elucidate hormonal effects and unique sex-specific disease mechanisms. A history of reproductive risk factors represents an opportunity for comprehensive risk factor screening, refinement of cardiovascular disease risk assessment, and implementation of primordial and primary prevention to optimize long-term cardiometabolic health in women.
•Independent of chronologic aging, menopause causes a proatherogenic shift in lipids.•Hormone therapy is not recommended for dyslipidemia or heart disease prevention.•Consideration of menopause ...status can optimize cardiac risk stratification.•Novel lipid-lowering agents can be utilized when lipid goals are not met with statins.
Dyslipidemia is an established risk factor for cardiovascular disease (CVD), which remains the leading cause of morbidity and mortality in women globally. The incidence of dyslipidemia increases over a woman's lifespan, with adverse changes around the time of menopause. Menopause, and the years leading up to the final menstrual period, is a time of estrogen fluctuation and ultimately estrogen deficiency, which has been associated with proatherogenic changes in the lipid profile. Independent of aging, menopausal status is associated with elevations in serum total cholesterol, LDL cholesterol, apolipoproteins, and triglycerides, and decreases in HDL cholesterol (HDL-C). Emerging research also suggests that after menopause there is a loss of functional HDL cardioprotective properties. Early initiation of menopausal hormone therapy (MHT) confers a favorable effect on lipid profile, though this does not translate into improved CVD outcomes and therefore guidelines do not indicate it for primary or secondary prevention of CVD. At the time of menopause, special consideration should be given to women with conditions more associated with CVD, including polycystic ovarian syndrome, premature menopause, early menopause, premature ovarian insufficiency, and familial hypercholesterolemia. Statins remain the mainstay of dyslipidemia therapy, though novel lipid-lowering agents are emerging. This review provides an overview of lipid alterations observed during the menopausal transition, summarizes the current evidence on the role of estrogen and progestogen on lipids, identifies special populations of women at especially high risk for lipid dysregulation at menopause, and describes approaches to the screening and treatment of midlife women.
Background Team-based models of cardio-obstetrics care have been developed to address the increasing rate of maternal mortality from cardiovascular diseases. Cardiovascular clinician and trainee ...knowledge and comfort with this topic, and the extent of implementation of an interdisciplinary approach to cardio-obstetrics, are unknown. Methods and Results We aimed to assess the current state of cardio-obstetrics knowledge, practices, and services provided by US cardiovascular clinicians and trainees. A survey developed in conjunction with the American College of Cardiology was circulated to a representative sample of cardiologists (N=311), cardiovascular team members (N=51), and fellows in training (N=139) from June 18, 2020, to July 29, 2020. Knowledge and attitudes about the provision of cardiovascular care to pregnant patients and the prevalence and composition of cardio-obstetrics teams were assessed. The widest knowledge gaps on the care of pregnant compared with nonpregnant patients were reported for medication safety (42%), acute coronary syndromes (39%), aortopathies (40%), and valvular heart disease (30%). Most respondents (76%) lack access to a dedicated cardio-obstetrics team, and only 29% of practicing cardiologists received cardio-obstetrics didactics during training. One third of fellows in training reported seeing pregnant women 0 to 1 time per year, and 12% of fellows in training report formal training in cardio-obstetrics. Conclusions Formalized training in cardio-obstetrics is uncommon, and limited access to multidisciplinary cardio-obstetrics teams and large knowledge gaps exist among cardiovascular clinicians. Augmentation of cardio-obstetrics education across career stages is needed to reduce these deficits. These survey results are an initial step toward developing a standard expectation for clinicians' training in cardio-obstetrics.
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