Hyperlipidemia and risk for preclampsia.

Hypertensive disorders of pregnancy are among the leading causes of maternal morbidity and mortality in the US. Preeclampsia (PreE) which includes hypertension and proteinuria during pregnancy, is thought to result from placental ischemia. Risk factors for PreE parallel those for cardiovascular disease, and recent studies point to hyperlipidemia specifically, hypertriglyceridemia, as a risk factor for PreE. Current practice does not routinely include lipid testing pre-conception or during pregnancy. Professional, societal recommendations should advocate for hyperlipidemia screening, followed by appropriate management, pre-conception and during pregnancy.

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 Panel's 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.

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.

JCL roundtable: Risk evaluation and mitigation strategy.

Many factors enter into the decision by the Food and Drug Administration (FDA) to approve a new drug for use by physicians and other health care providers in treating diseases. Initially, the FDA authority was restricted to issues of safety and only later did the documentation of efficacy become part of the review process required for approval. However, all drugs have the potential for causing harm at some dose level to all and at lower doses in certain patients with vulnerability to the particular pharmacology of the agent. As new drugs have been designed to manage disorders that are uncommon, but of significant consequence, they may have adverse effects that are acceptable only because they are so uniquely beneficial to these specific conditions. The risk of these adverse effects may be acceptable since the benefit can outweigh the harm in most patients and the adversity can be predicted and managed. The approval of this category of drugs has grown rapidly since definition of a mechanism of action to manage and modify the risk has been provided by a process known as known as Risk Evaluation and Mitigation Strategy or "REMS." In 2007, the Food and Drug Administration Amendments Act (FDAAA) allowed the FDA to require postmarketing studies and the authority to mandate the implementation of a REMS for drugs with efficacy but documented potential for harm. Two relatively new drugs useful in the management of severe elevations of low-density lipoprotein cholesterol have been approved under a requirement for a REMS. These are lomitapide, an inhibitor of microsomal triglyceride transfer protein and mipomersen, an antisense oligonucleotide which reduces the synthesis of apolipoprotein B.

Statins in the Management of Pediatric Dyslipidemia.

Hypercholesterolemia is a major concern in the USA, with studies identifying children as young as 2years old with early-stage atherosclerosis. Genetics play a major role in the dyslipidemia of children, but other factors, such as diet and lack of physical activity, confound the problem. Familial hypercholesterolemia (FH) is a genetic condition that causes lifelong elevations in low-density lipoprotein cholesterol (LDL-C). The heterozygous form of the disease affects around 1 in 200 people, and the homozygous form of the disease affects around 1 in 160,000-300,000 people. Early identification and appropriate management of patients with FH are essential to reduce cardiovascular disease morbidity and mortality. Consequently, US dyslipidemia guidelines recommend routine screening of all children aged 9-11years, and that LDL-C levels should be <110mg/dL in children and adolescents. The primary management strategy in all children with dyslipidemia is diet and lifestyle; a healthy diet (including fruits, vegetables, fish, and whole grains) and increased physical activity should be encouraged. Most patients with FH will also require pharmacotherapy to reduce LDL-C levels to ≤130mg/dL. Statins are recommended as first-line therapy due to their proven efficacy in reducing LDL-C and improving other lipid parameters in children. They have also been shown to have a positive effect on atherosclerosis. Safety is of particular concern with children; however, studies have so far shown that the side-effect profile of statins in children is similar to that in adults. Despite improvements in disease management, FH remains underdiagnosed and undertreated, highlighting the need for greater awareness and understanding.

National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2.

An Expert Panel convened by the National Lipid Association previously developed a consensus set of recommendations for the patient-centered management of dyslipidemia in clinical medicine (part 1). These were guided by the principle that reducing elevated levels of atherogenic cholesterol (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) reduces the risk for atherosclerotic cardiovascular disease. This document represents a continuation of the National Lipid Association recommendations developed by a diverse panel of experts who examined the evidence base and provided recommendations regarding the following topics: (1) lifestyle therapies; (2) groups with special considerations, including children and adolescents, women, older patients, certain ethnic and racial groups, patients infected with human immunodeficiency virus, patients with rheumatoid arthritis, and patients with residual risk despite statin and lifestyle therapies; and (3) strategies to improve patient outcomes by increasing adherence and using team-based collaborative care.

Novel treatments for familial hypercholesterolemia: pharmacogenetics at work.

The familial hypercholesterolemias (FHs) are inherited disorders of lipoprotein metabolism that are among the most prevalent genetically inherited disorders. Various genetic mutations ultimately lead to greatly increased low-density lipoprotein-cholesterol (LDL-C) levels over a lifetime. Consequently, patients with FH develop coronary artery disease at significantly earlier ages and at a greater frequency than the general population. Current therapies revolve around aggressive lifestyle modifications, cholesterol-lowering medications, and in some cases LDL apheresis. Despite maximal medical therapy, LDL-C is not sufficiently reduced in some patients, and they remain at a substantially increased risk of coronary heart disease. Recent advances in genetic-based pharmacology have enabled the development of three novel classes of medications for FH. Two of those compounds, mipomersen and lomitapide, result in decreased LDL-C production and were approved by the Food and Drug Administration in the past 18 months for treatment of homozygous FH. Mipomersen is an antisense oligonucleotide that inhibits the translation of apolipoprotein B-100, and lomitapide is an inhibitor of the microsomal triglyceride transfer protein, which prevents the incorporation of triglycerides into lipoproteins. A third class of drugs, the proprotein convertase subtilisin/kexin type 9 inhibitors, is still in development, although studies in patients with heterozygous or receptor-defective homozygous FH have demonstrated substantial reductions in LDL-C by decreasing the degradation of LDL receptors. Development of these novel treatments for hypercholesterolemia resulted from the application of known genetic mutations and is the focus of this review.

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.

Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia.

The familial hypercholesterolemias (FH) are a group of genetic defects resulting in severe elevations of blood cholesterol levels and increased risk of premature coronary heart disease. FH is among the most commonly occurring congenital metabolic disorders. FH is a treatable disease. Aggressive lipid lowering is necessary to achieve the target LDL cholesterol reduction of at least 50% or more. Even greater target LDL cholesterol reductions may be necessary for FH patients who have other CHD risk factors. Despite the prevalence of this disease and the availability of effective treatment options, FH is both underdiagnosed and undertreated, particularly among children. Deficiencies in the diagnosis and treatment of FH indicate the need for greatly increased awareness and understanding of this disease, both on the part of the public and of healthcare practitioners. This document provides recommendations for the screening, diagnosis and treatment of FH in pediatric and adult patients developed by the National Lipid Association Expert Panel on Familial Hypercholesterolemia. This report goes beyond previously published guidelines by providing specific clinical guidance for the primary care clinician and lipid specialist with the goal of improving care of patients with FH and reducing their elevated risk for CHD.

Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia.

The familial hypercholesterolemias (FH) are a group of genetic defects resulting in severe elevations of blood cholesterol levels and increased risk of premature coronary heart disease. FH is among the most commonly occurring congenital metabolic disorders. FH is a treatable disease. Aggressive lipid lowering is necessary to achieve the target LDL cholesterol reduction of at least 50% or more. Even greater target LDL cholesterol reductions may be necessary for FH patients who have other CHD risk factors. Despite the prevalence of this disease and the availability of effective treatment options, FH is both underdiagnosed and undertreated, particularly among children. Deficiencies in the diagnosis and treatment of FH indicate the need for greatly increased awareness and understanding of this disease, both on the part of the public and of healthcare practitioners. This document provides recommendations for the screening, diagnosis and treatment of FH in pediatric and adult patients developed by the National Lipid Association Expert Panel on Familial Hypercholesterolemia. This report goes beyond previously published guidelines by providing specific clinical guidance for the primary care clinician and lipid specialist with the goal of improving care of patients with FH and reducing their elevated risk for CHD.

Anaphylactoid-like reactions in a patient with HyperLp(a)lipidemia undergoing LDL apheresis with dextran sulfate adsorption and herbal therapy with the spice turmeric.

Elevated Lipoprotein (a) (Lp(a)) levels are associated with atherosclerosis and are independent risk factors for coronary artery disease and stroke [Ariyo et al., N Engl J Med 2003;349:2108­2115; Price et al., Atherosclerosis 2001;157:241­249]. Low-density lipoprotein (LDL)-apheresis is the most effective therapy for reducing Lp(a) levels [Parker, Chem Phys Lipids 1994;67­68:331­338; Stefanutti et al., Transfus Apher Sci 2010;42:21­26]. Dextran sulfate-cellulose adsorption (Liposorber®) removes both LDL and Lp(a) particles with minimal effect on high-density lipoprotein levels. During the procedure, high levels of bradykinin are generated as the kallikrein-kinin system is activated by contact with the negatively charged dextran-sulfate cellulose [Krieter et al., Artif Organs 2005;29:47­52]. Bradykinin is a potent vasodilator and a substrate of the angiotension converting enzyme (ACE). ACE inhibitors are contraindicated for apheresis procedures because these drugs prevent bradykinin degradation, which causes anaphylatoid reactions characterized by hypotension, bradycardia, dyspnea, and flushing [Owen and Brecher, Transfusion 1994;34:891­894]. Turmeric is a yellow spice that is used as an herbal remedy to treat a myriad of conditions ranging from abdominal pain to pulmonary infections. Scientific investigations of the ethnomedicinal properties of curcumin, the major derivative of turmeric, suggest that this compound has anti-inflammatory, antioxidant, and antineoplastic properties [Lobo et al., J Pharm Pharmacol 2009;61:13­21]. We report a case of a patient undergoing Liposorber® therapy for treatment of hyperLp(a)lipidemia who had three episodes of anaphylactoid-like reactions after starting therapy with the spice turmeric.

Catholic Health Initiatives at 10.

The summer of 2006 marked the 10th anniversary of the formation of Denver-based Catholic Health Initiatives (CHI). Formed in 1996 as the result of the merger of three Catholic health care systems, and soon joined by a fourth, the system integrated a diverse collection of health care facilities previously sponsored by 12 different religious congregations. It was the first Catholic health system to give laity a sponsorship role in its facilities. CHI's facilities are sponsored by a public juridic person (PJP), the Catholic Health Care Federation (CHCF). The same people who sit on the system's board also constitute CHCF. They are thus responsible for both governance and sponsorship. CHI was the first Catholic health care system to give laypersons a sponsorship role in its facilities. Establishing the PJP was a long and complex task. Eventually, the church determined that CHI's PJP should be pontifical, accountable to the Congregation for Institutes of Consecrated Life and Societies of Apostolic Life in Rome. CHCF in 1991 became the first PJP in health care in the United States. CHI's staff, led by its first president and chief executive officer, Patricia Cahill, quickly took steps to help the new system begin to coalesce, establishing a single, systemwide pension plan, debt policy, and so forth. Also challenging was the creation of a systemwide new culture. An essential step in the development of CHI's culture was the involvement of employees in the identification of its core values: reverence, integrity, compassion, and excellence, The creation of CHI's Mission and Ministry Fund also helped give the system an identity. This fund provides grants to programs that take an innovative approach to building healthy communities, a goal expressed in CHI's mission and vision statements. The people who created CHI and nurtured it during its first decade give it high marks for faithful adherence to its mission. Even so, they acknowledge that there is always more work to be done.

Long-term effects of LDL apheresis in patients with severe hypercholesterolemia.

Familial hypercholesterolemia (FH) is an inherited disorder of lipoprotein metabolism involving mutations in the LDL receptor (LDL-R). Patients with mutation in one (heterozygous) or both (homozygous) genes have markedly elevated LDL cholesterol and are at increased risk for coronary heart disease (CHD). Aggressive lipid lowering is required for homozygous and many heterozygous FH patients. This often involves LDL-apheresis, where LDL and other apo-B containing lipoproteins are selectively removed from the plasma. We have retrospectively studied 34 patients treated with biweekly LDL-apheresis at the Hospital of the University of Pennsylvania. In our patient population, adverse events were uncommon and rarely resulted in shortened treatment time. There was a dramatic decrease in the relative risk of cardiovascular events and cardiovascular interventions in patients treated with LDL-apheresis for an average of 2.5 years. Some but not all patients had long-term reduction in their LDL levels as a result of LDL-apheresis, suggesting that time-averaged reduction in LDL and/or LDL:HDL ratios were responsible for clinical improvement. These data support the use of LDL-apheresis in patients with FH, as well as medication-intolerant patients that have elevated LDL cholesterol despite maximal pharmacological treatment.

Home testing: friend or foe?

Though more patients seek out home tests, nurses find pros and cons associated with their use.

Identification and management of vascular risk: beyond low density lipoprotein cholesterol.

Vascular disease is basically an inherited metabolic disease. Eighty percent of individuals who develop disease have the same blood cholesterol levels as individuals who do not develop disease. With vascular disease pervasive throughout the world and current assessment techniques insufficient to identify those at risk, use of a multifactorial approach to vascular assessment is prudent. Assays are currently available that enable health care providers to determine risk beyond those traditionally used. These "novel" risk factors appear to be additive (Brown, 2001; Rader, 2000a, 2002; Superko, 1995), and when combined with traditional factors, LDL can be adjusted to prevent disease. In individuals with established disease, these factors can be instrumental in identifying an appropriate treatment protocol for halting the progression of disease. To date, the health care establishment as a whole has done a poor job of identifying and thoroughly treating cardiovascular risk. Even when risks were identified, often treatment protocols have not been aggressive enough to reach targeted goals (Hoerger, 1998; Jacobson, 2000; NHANES III, 2000). The unique role of the occupational health nurse offers an opportunity to follow a client during long periods of time. This is useful in establishing trust and getting to know the specific problems of each individual. The occupational health nurse, therefore, stands at the threshold of change for the client, easing and assisting the client to reach individual goals. This group of nurses can play a significant role in forging prevention and stamping out the number one killer of the American population.