James Underberg

Rationale and design of the familial hypercholesterolemia foundation CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia registry

BACKGROUND Familial hypercholesterolemia (FH) is a hereditary condition caused by various genetic mutations that lead to significantly elevated low-density lipoprotein cholesterol levels and resulting in a 20-fold increased lifetime risk for premature cardiovascular disease. Although its prevalence in the United States is 1 in 300 to 500 individuals, <10% of FH patients are formally diagnosed, and many are not appropriately treated. Contemporary data are needed to more fully characterize FH disease prevalence, treatment strategies, and patient experiences in the United States. DESIGN The Familial Hypercholesterolemia Foundation (a patient-led nonprofit organization) has established the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE FH) Registry as a national, multicenter initiative to identify US FH patients, track their treatment, and clinical and patient-reported outcomes over time. The CASCADE FH will use multiple enrollment strategies to maximize identification of FH patients. Electronic health record screening of health care systems will provide an efficient mechanism to identify undiagnosed patients. A group of specialized lipid clinics will enter baseline and annual follow-up data on demographics, laboratory values, treatment, and clinical events. Patients meeting prespecified low-density lipoprotein or total cholesterol criteria suspicious for FH will have the opportunity to self-enroll in an online patient portal with information collected directly from patients semiannually. Registry patients will be provided information on cascade screening and will complete an online pedigree to assist with notification of family members. SUMMARY The Familial Hypercholesterolemia Foundation CASCADE FH Registry represents a novel research paradigm to address gaps in knowledge and barriers to comprehensive FH screening, identification, and treatment.

ACCF/AHA/ACP 2009 Competence and Training Statement: A Curriculum on Prevention of Cardiovascular Disease

Jonathan L. Halperin, MD, FACC, Chair Mark A. Creager, MD, FACC, FAHA[†††][1] Gordon L. Fung, MD, PhD, FACC, FAHA David R. Holmes, Jr, MD, FACC[‡‡‡][2] Geno J. Merli, MD, FACP Ira S. Nash, MD, FACC, FACP L. Kristin Newby, MD, FACC, FAHA Ileana Pina, MD, FACC, FAHA George P.

ACCF/AHA/ACP 2009 Competence and Training Statement: A Curriculum on Prevention of Cardiovascular Disease: A Report of the American College of Cardiology Foundation/American Heart Association/American College of Physicians Task Force on Competence and Training (Writing Committee to Develop a Competence and Training Statement on Prevention of Cardiovascular Disease)

The mission of many organizations is the optimal care to those with or at risk for developing CVD (primary and secondary prevention). Over the past two decades, there have been dramatic increases in knowledge concerning specific risk factors in atherosclerosis, hypertension, thrombosis, and other forms of vascular dysfunction. Clinical trials have proven that strategies aimed at the appropriate detection and modification of risk factors can slow progression of atherosclerosis, diabetes mellitus, and hypertension and reduce the occurrence of clinical cardiovascular events in both primary and secondary prevention settings. More recently, it has been shown that atherosclerosis can be stabilized or even modestly reversed. Finally, a new and growing knowledge base of molecular genetics applied to the study of the cardiovascular system has potential relevance to the clinical practice of preventive cardiovascular medicine. Despite the fact that clinical outcomes can be improved by promotion of favorable life habits and behaviors and by the proper use of drug treatment, the application of primary and secondary preventive interventions in clinical practice is not optimal. Prevention of CVD in both the primary and secondary prevention setting, while dominantly the responsibility of the primary care provider, is increasingly challenged given this ever expanding new knowledge as well as the ongoing problems related to adherence to recommendations. New knowledge in the area of pre-clinical disease detection has presented increasingly challenging scenarios to primary care healthcare providers relative to the decisions regarding the need for further risk stratification and aggressive medical regimens. Furthermore, increasingly complex patients are surviving with CVD, many of whom can benefit from advanced knowledge and expertise with regard to risk factor management and rehabilitation that is beyond traditional general primary and cardiology practitioners scope of practice. The prevention of cardiovascular morbidity and mortality is a shared responsibility among all health professionals involved in the care of people at risk of developing cardiovascular disease. This document is directed at those individuals seeking expertise at a leadership level in this field, and includes opportunities for formal training and alternative routes to competence and maintenance of competence in prevention of cardiovascular disease (Table 2), and educational resources for acquisition and maintenance of competence in the prevention of cardiovascular disease (Table 3). To address the expanding fund of knowledge in the area and to ensure that an adequately trained force of preventive cardiovascular leaders will be available to primary care providers, as well as provide a pool of providers with expertise in running rehabilitation and other programs designed to address the ongoing issue of adherence, the formulation of clinical competency criteria for the cardiovascular preventive specialist is needed. These competency criteria are expected to address issues of expert clinical and scientific leadership, specialty patient care and consultation, and directorship of primary and secondary preventive cardiac programs. Of note and similar to other subspecialty areas of medicine, cardiovascular preventive specialists will have varying areas of expertise and will not necessarily achieve all the outlined areas of competencies. These clinical competency criteria in the area of specialty treatment and prevention of CVD are needed given the current setting of a rapidly growing field of knowledge ranging from molecular and cellular mechanisms to clinical outcomes in order to translate into improved patient care. Table 2 Opportunities for Formal Training and Alternative Routes to Competence and Maintenance of Competence in Prevention of Cardiovascular Disease Table 3 Educational Resources for Acquisition and Maintenance of Competence in the Prevention of Cardiovascular Disease C. Noel Bairey Merz, MD, FACC, FAHA Chair, ACCF/AHA/ACP Clinical Competence Statement on Prevention of CVD

Update on the use of PCSK9 inhibitors in adults: Recommendations from an Expert Panel of the National Lipid Association

An Expert Panel convened by the National Lipid Association was charged with updating the recommendations on the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody therapy that were provided by the 2015 National Lipid Association Recommendations for the Patient-Centered Management of Dyslipidemia: Part 2. Recent studies have demonstrated the efficacy of these agents in reducing low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and have confirmed their excellent safety profile. A cardiovascular outcomes study has shown that these agents reduce incident atherosclerotic cardiovascular disease (ASCVD) events in patents with stable ASCVD and concomitant risk factors. The current update provides the Expert Panels evidence-based recommendations on the clinical utility of PCSK9 inhibitors in patients with stable ASCVD, progressive ASCVD, LDL-C ≥ 190 mg/dL (including polygenic hypercholesterolemia, heterozygous familial hypercholesterolemia and the homozygous familial hypercholesterolemia phenotype) and very-high-risk patients with statin intolerance.

Systematic Review: Evaluating the Effect of Lipid-Lowering Therapy on Lipoprotein and Lipid Values

PurposeThis systematic review was performed to summarize published experience using low density lipoprotein particle number (LDL-P) to monitor the efficacy of lipid-lowering pharmacotherapies.MethodsStudies were identified from a literature search of MEDLINE (January 1, 2000 – June 30, 2012); and abstract searches of select conferences. All accepted studies reported mean (or median) nuclear magnetic resonance (NMR)-based LDL-P values for at least 10 subjects receiving lipid lowering pharmacotherapy.ResultsSearches revealed 36 studies (with 61 treatment arms) in which LDL-P measurements were reported pre- and post-treatment. Most studies also reported changes in low-density lipoprotein cholesterol (LDL-C), but fewer studies reported changes in apolipoprotein B (apoB)(n = 20) and non-HDL-C (n = 28). Treatments included statins (22 arms/15 studies), fibrates (7 arms/7studies), niacin (7 arms/6 studies), bile acid sequestrants (5 arms/2 studies), an anti-apoB oligonucleotide (2 arms/2 studies), combination therapies (8 arms/6 studies), anti-diabetics (5 arms/4 studies), and, other treatments (5 arms/2 studies). Lipid-lowering pharmacotherapy resulted in reductions in mean LDL-P in all but two studies. In several statin studies, the percent reductions in LDL-P were smaller than reductions in LDL-C, comparable changes were reported when LDL-P and apoB, were reported.ConclusionsStudy-level data from this systemic review establish that different lipid lowering agents can lead to discordance between LDL-P and LDL-C, therefore, basing LDL-lowering therapy only on the achievement of cholesterol goals may result in a treatment gap. Therefore, the use of LDL-P for monitoring lipid-lowering therapy, particularly for statins, can provide a more accurate assessment of residual cardiovascular risk.

PCSK9 inhibitor access barriers—issues and recommendations: Improving the access process for patients, clinicians and payers

The proprotein convertase subtilisin/kexin type 9 inhibitors or monoclonal antibodies likely represent the greatest advance in lipid management in 30 years. In 2015 the US Food and Drug Administration approved both alirocumab and evolocumab for high‐risk patients with familial hypercholesterolemia (FH) and clinical atherosclerotic cardiovascular disease requiring additional lowering of low‐density lipoprotein cholesterol. Though many lipid specialists, cardiovascular disease prevention experts, endocrinologists, and others prescribed the drugs on label, they found their directives denied 80% to 90% of the time. The high frequency of denials prompted the American Society for Preventive Cardiology (ASPC), to gather multiple stakeholder organizations including the American College of Cardiology, National Lipid Association, American Association of Clinical Endocrinologists (AACE), and FH Foundation for 2 town hall meetings to identify access issues and implement viable solutions. This article reviews findings recognized and solutions suggested by experts during these discussions. The article is a product of the ASPC, along with each author writing as an individual and endorsed by the AACE.

Use of health information technology (HIT) to improve statin adherence and low-density lipoprotein cholesterol goal attainment in high-risk patients: Proceedings from a workshop

The workshop discussions focused on how low-density lipoprotein cholesterol (LDL-C) goal attainment can be enhanced with the use of health information technology (HIT) in different clinical settings. A gap is acknowledged in LDL-C goal attainment, but because of the passage of the American Recovery & Reinvestment Act and the Health Information Technology for Economic and Clinical Health Acts there is now reason for optimism that this gap can be narrowed. For HIT to be effectively used to achieve treatment goals, it must be implemented in a setting in which the health care team is fully committed to achieving these goals. Implementation of HIT alone has not resulted in reducing the gap. It is critical to build an effective management strategy into the HIT platform without increasing the overall work/time burden on staff. By enhancing communication between the health care team and the patient, more timely adjustments to treatment plans can be made with greater opportunity for LDL-C goal attainment and improved efficiency in the long run. Patients would be encouraged to take a more active role. Support tools are available. The National Lipid Association has developed a toolkit designed to improve patient compliance and could be modified for use in an HIT system. The importance of a collaborative approach between nongovernmental organizations such as the National Lipid Association, National Quality Forum, HIT partners, and other members of the health care industry offers the best opportunity for long-term success and the real possibility that such efforts could be applied to other chronic conditions, for example, diabetes and hypertension.

LOWER, a registry of lomitapide-treated patients with homozygous familial hypercholesterolemia: Rationale and design

BACKGROUND Lomitapide is an orally active selective inhibitor of microsomal triglyceride transfer protein approved as adjunctive therapy for homozygous familial hypercholesterolemia (HoFH). The Lomitapide Observational Worldwide Evaluation Registry (LOWER) is a global, long-term, prospective, observational treatment registry established as a regulatory requirement. OBJECTIVES LOWER will evaluate the long-term safety and effectiveness of lomitapide in clinical practice. The objectives include evaluation of the occurrence of events of special interest and assessment of the long-term effectiveness of lomitapide in maintaining reduced serum lipid levels. METHODS LOWER is a noninterventional study open to eligible lomitapide-treated patients. At least 300 patients will be enrolled and followed for at least 10 years. Data will be collected in conjunction with usual care visits and analyzed annually. LOWER includes a cardiovascular imaging substudy; an independent pregnancy exposure registry is also open. RESULTS Events of special interest include hepatic abnormalities, gastrointestinal events, certain gastrointestinal tumors, major adverse cardiovascular events, and events associated with coagulopathy. Data will be collected on demographics, diagnosis, patient history, lomitapide dosing, concomitant treatment, lipid profile, and other laboratory results. CONCLUSION LOWER will assess the long-term safety, efficacy, and patterns of use of lomitapide, increase understanding of the benefit-to-risk profile, and add to knowledge of HoFH.

Laparoscopic gastric banding resolves the metabolic syndrome and improves lipid profile over five years in obese patients with body mass index 30–40 kg/m2

BACKGROUND Obesity, metabolic syndrome (MS) and dyslipidemia are independent risk factors for cardiovascular disease. Bariatric surgery is increasingly recognized as an effective intervention for improving each of these risk factors. There are sparse data on the long-term durability of metabolic changes associated with bariatric surgery, in particular with laparoscopic gastric banding (LGB). Our objective was to evaluate the durability of metabolic changes associated with LGB in nonmorbid obesity. METHODS Fifty obese patients (BMI 30-40) with ≥1 obesity-related comorbidity were prospectively followed for five years. At follow-up, subjects underwent fasting blood measures, including lipid NMR spectroscopy and standard lipid profile. RESULTS Forty-seven patients (45 female, mean age 43.8 years) completed four years follow-up (46 completed five years). Baseline BMI was 35.1 ± 2.6. Subjects exhibited mean weight loss of 22.3 ± 7.9 kg (22.9 ± 7.4%) at year one and maintained this (19.8 ± 10.2%) over five years. At baseline, 43% (20/47) of subjects met criteria for MS. This was reduced to 15% (7/47) at year one and remained reduced over five years (13%, 6/46) (p < 0.001). There were reductions in triglycerides (p < 0.001) and increases in HDL cholesterol (HDL-C, p < 0.001) and HDL particle concentration (p = 0.02), with a trend toward increased HDL particle size (p = 0.06) at year five. Changes in triglycerides and HDL-C were more prominent in patients with MS at baseline, but unassociated with weight loss or waist circumference. Changes in HDL particle size and concentration were not associated with MS status, weight loss, waist circumference, or statin use. CONCLUSIONS LGB produces significant weight loss, resolution of MS and changes in lipid profile suggestive of beneficial HDL remodeling. These changes persist five years following LGB.

Resistant Hypertension and Sleep Apnea: Pathophysiologic Insights and Strategic Management

Resistant hypertension is common among adults with hypertension affecting up to 30% of patients. The treatment of resistant hypertension is important because suboptimal blood pressure control is the leading preventable cause of death worldwide. A frequent comorbid condition in patients with resistant hypertension is obstructive sleep apnea. The pathophysiology of sleep apnea–associated hypertension is characterized by sustained adrenergic activation and volume retention often posing treatment challenges in patients with resistant hypertension. This review will address some of the epidemiologic data associating apnea with the pathogenesis of resistant hypertension. Diagnosis and management of apnea and its associated hypertension will also be considered.