Dyslipidemia Screening and Management in Primary Care Practice: A Look Beyond the Numbers
Deepak Honaganahalli, MD, MPH
ABSTRACT: One-third of US adults have elevated low-density lipoprotein cholesterol levels, a condition that is most often diagnosed and treated in primary care. Appropriate screening helps identify these patients with dyslipidemia. As the understanding of the science behind cholesterol management has evolved, numerous guidelines have become available to help clinicians appropriately evaluate and treat dyslipidemia and focus on reducing the associated cardiovascular risk. Multiple medications classes are available to treat different kinds of dyslipidemia, particularly familial hypercholesterolemia. Patients with complicated cases of dyslipidemia can be referred to lipidologists for comanagement along with their primary care provider.
KEYWORDS: Dyslipidemia, coronary heart disease, low-density lipoprotein cholesterol, familial hypercholesterolemia, cholesterol treatment guidelines
The approach to evaluation and management of dyslipidemia has undergone a revolution in recent years. Advances in the understanding of cholesterol metabolism have opened new avenues in the treatment of dyslipidemia and the reduction of the associated cardiovascular risk.
More than one-third of patients seen in primary care in the United States have dyslipidemia,1 which is most often diagnosed and treated in the primary care setting.1 Based on statistical data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES), an estimated 71 million (33.5%) US adults aged 20 years and older had high levels of low-density lipoprotein cholesterol (LDL-C), only 34 million (48.1%) of whom were being treated and only 23 million (33.2%) of whom had achieved control of LDL-C levels.1
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Patients with dyslipidemia also often have associated comorbid conditions and other barriers to treatment that must be considered in the management of the condition. Dyslipidemia can have either genetic causes (primary dyslipidemia) or lifestyle-related causes (secondary dyslipidemia).2 The most common primary cause of elevated LDL-C is familial hypercholesterolemia (FH).3 FH is a frequent cause of premature coronary heart disease (CHD) and can be transmitted in a homozygous or a heterozygous pattern.3 Approximately 20% of acute coronary events occurring in persons younger than 45 years in the US general population are attributable to FH.3
Agents in a newer class of medications, the proprotein convertase subtilisin-like kexin type 9 (PCSK9) inhibitors, have recently become available and are potent in reducing LDL-C levels.4
This article is a brief introduction on how to change our thinking to move beyond cholesterol laboratory numbers in the primary care setting. It also briefly discusses how to provide patient-centered medical care to reduce cardiovascular risk. It also discusses the prevalence of FH in the author’s community health center and the challenges encountered in collecting this information.
Prevalence of Dyslipidemia
According to statistics from the Centers for Disease Control and Prevention, approximately 33.5% of US adults aged 20 and older have elevated LDL-C levels.1 And less than half of those patients receive treatment.1 NHANES data show that the prevalence of elevated LDL-C increases with age and is 11.7% in the 20 to 39 age group, 41.2% in the 40 to 64 age group, and 58.2% for the 65 and older age group.1 Heterozygous FH occurs with a frequency of approximately 1 in 300 to 1 in 500 in the general population, and homozygous FH occurs in approximately 1 in 1 million in the general population, except in certain special populations such as French Canadians, Christian Lebanese, Dutch Afrikaners, Ashkenazi Jews, and Asian Indians.3
Due to high prevalence of dyslipidemia in the United States, every health care provider should screen all children and adults for hypercholesterolemia. Expert guidelines strongly recommend universal screening with a fasting lipid panel (FLP) at ages 9 to 11 years to identify all children with genetic causes of hyperlipidemia.5 Screening should occur earlier (before 2 years of age) if there is a strong positive family history of hypercholesterolemia or premature CHD or the presence of other major CHD risk factors.3 Furthermore, the US Preventive Services Task Force6 strongly recommends screening men aged 35 and older and women aged 45 and older for lipid disorders. It also recommends screening men aged 20 to 35 years and women aged 20 to 45 years for lipid disorders if they are at increased risk for CHD.6
Make Early Diagnosis to Prevent Early Deaths (MEDPED), a research project and a nonprofit organization whose goal is helping to treat people with inherited cholesterol disorders such as FH, initiated cascade screening for primary dyslipidemia as a cost-effective strategy to diagnose FH, given its low prevalence.7 It is a process of screening close relatives of patients who already have received a diagnosis of FH, in order to increase the probability of identification of other persons with the condition.7
NEXT: Thinking Beyond the Numbers
Thinking Beyond Numbers
Dyslipidemia is not simply elevated total cholesterol (TC) and triglycerides (TG) numbers or low high-density lipoprotein cholesterol (HDL-C) or LDL-C numbers. Laboratories offer a standard normal range for each of these categories, which leads to subjective interpretation and the possible overtreatment or undertreatment of dyslipidemia.
As with any other medical condition, the interpretation of dyslipidemia should be individualized, incorporating patients’ demographic data and comorbid conditions. Numerous guidelines are available for the evaluation and management of dyslipidemia, notably among them those of the National Cholesterol Education Program’s Adult Treatment Panel III.8 In 2013, the American College of Cardiology and the American Heart Association published guidelines incorporating randomized, controlled trials (RCTs) and created a different approach for dyslipidemia management that streamlines the interpretation process.9,10 And, in 2015, the National Lipid Association incorporated other studies along with RCTs and developed recommendations on the patient-centered management of dyslipidemia to help tailor therapy to individual patients.11,12
Evaluation and management
There are 3 broad subclasses of lipoproteins. Levels of one or more of these lipoprotein subclasses may be abnormal. Elevated LDL-C is the major risk factor for CHD. Guidelines discuss target goals of LDL-C and non-HDL-C levels to reduce the risk of CHD.8 But in the primary care setting, elevated LDL-C is commonly a result of secondary causes.3 Lifestyle interventions are the essential part of management.
Primary disorders are evaluated based on family history, physical examination findings, and laboratory test results, with advanced testing used in select cases.3 FLP results showing elevated TC and LDL-C suggest the presence of FH. In the general population, the probability of the presence of FH is approximately 80% when the LDL-C level is greater than 250 mg/dL in patients aged 30 years or older, greater than 220 mg/dL in patients aged 20 to 29 years, and greater than 190 mg/dL in patients younger than 20 years of age.3,13 A patient with a personal or family history of premature CHD and physical findings of tendinous xanthomas, tuberous xanthomas, or corneal arcus all should warrant suspicion for FH.3,13
Numerous clinical diagnostic tools are available to help primary care providers diagnose FH, including diagnostic criteria from the Simon Broome Register Group, the Dutch Lipid Clinic Network, and MEDPED.13 Although gene mutation is the gold standard for diagnosis, it is helpful only if the mutation has already been identified in the family.3 It is worth noting that even after applying all of the FH diagnostic criteria, only 1 in 25 persons in the general population would receive a diagnosis of FH, due to the wide variety of secondary causes such as random variation, dietary effects, and familial polygenic influences.3
Local Prevalence of FH
We attempted to identify the prevalence of FH in our community health center patient population. Our business intelligence department generated cross-sectional data on the age-based LDL-C levels of our patients in April 2015. Our facility serves approximately 80,000 patients. Among them, 32,577 were screened with an FLP. Using MEDPED age-based LDL-C cutoff criteria, 36 patients aged 30 years or older had an LDL-C level greater than 250 mg/dL, 3 patients from 20 to 29 years of age had an LDL-C level greater than 220 mg/dL, and 1 patient younger than 20 years of age had an LDL-C level greater than 190 mg/dL. Based on these data, the estimated prevalence of possible FH in our population appears to be approximately 1 in 800. The screening rate is 40.7%, or 1 of every 2.5 patients seen. In comparison, general population-based studies have shown a US prevalence of FH of 1 in 300 to 1 in 500.3
While generating these data, we noted that patients had not been screened appropriately according to published dyslipidemia screening guidelines. For some of the patients who had elevated LDL-C levels, data about physical examination findings, family history, and other history were missing from the medical records. Some patients had had their laboratory tests performed at different facilities, and some of this information was unavailable. These factors likely contributed to the comparatively low prevalence of FH identified in our patient population.
Pharmacotherapy for elevated LDL-C levels includes statins, ezetimibe, and bile-acid sequestrants. PCSK9 inhibitors are now available for the treatment of FH in statin-intolerant patients and patients with CHD who are not at goal LDL-C levels.4,9,11,12
The most common causes of hypertriglyceridemia are related to diet and overweight. A TG level above 1000 mg/dL increases the risk for pancreatitis. Suspect hyperchylomicronemia if the TC to TG ratio is greater than 1 to 8. Nonpharmacologic therapy includes a fat-restrictive diet for hyperchylomicronemia and a carbohydrate-restrictive diet for hypertriglyceridemia. Diet, physical activity, and weight loss are effective long-term therapies. Pharmacologic therapy includes fibric acid derivatives, fish oils, and niacin. Of note, bile-acid sequestrants are contraindicated in hypertriglyceridemia because they increase TG levels.2,14
HDL-C is involved in reverse cholesterol transportation, and clinical trials of medications aimed at increasing HDL-C levels (cholesteryl ester transfer protein inhibitors) are ongoing, and results so far have been inconclusive.15 Low HDL-C levels might be a sign of insulin resistance syndrome. Most HDL-C treatments should be based on lifestyle interventions such as aerobic and resistance exercises, smoking cessation, weight loss, and a diet rich in monounsaturated or polyunsaturated fatty acids.8,9,11
With advances in understanding of dyslipidemia come insights into risk calculation and therapeutics. Advances also are happening in the areas of adiposity, inflammation, and newer classes of pharmacotherapeutic agents, discussion of which is beyond the scope of this article.
The most important reason for dyslipidemia treatment is to reduce CHD risk. Patient-centered intervention could increase the probability of patient adherence to lifelong treatment. To build that long-term therapeutic relationship, primary care providers should constantly encourage lifestyle interventions, monitor for new comorbid conditions, evaluate for CHD risk, and guide treatment according to evidence-based guidelines. Increased awareness about FH among primary care providers could have long-term health and socioeconomic impacts by preventing CHD morbidity and reducing health care costs.
In busy primary care practices, it is difficult to screen patients for dyslipidemia, apply the appropriate guidelines, calculate patient risk, recommend and initiate therapy, and then monitor that therapy. Patients with dyslipidemia may be referred for further consultation to clinical lipidologists, who are trained specifically to treat these patients. Primary care providers seeking to further develop their knowledge base may acquire education and certification through the National Lipid Association (http://www.lipid.org) or the American Board of Clinical Lipidology (http://www.lipidboard.org). Team-based care with other health professionals can also aid in this endeavor.
Deepak Honaganahalli, MD, MPH, is a board-certified internist at Peak Vista Community Health Centers in Colorado Springs, Colorado, and an assistant clinical professor of medicine at the University of Colorado School of Medicine in Aurora.
- Centers for Disease Control and Prevention (CDC). Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol — United States, 1999–2002 and 2005–2008. MMWR Morb Mortal Wkly Rep. 2011;60(4):109-114.
- Durrington P. Dyslipidaemia. Lancet. 2003;362(9385):717-731.
- Hopkins PN, Toth PP, Ballantyne CM, Rader DJ. Familial hypercholesterolemias: prevalence, genetics, diagnosis and screening recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5(3 suppl):S9-S17.
- Bottenberg BA, Bloch MJ. PCSK9 inhibitors for LDL cholesterol reduction: emerging clinical perspectives. Consultant. 2016;56(4):324-336.
- Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: summary report. Pediatrics. 2011;128(suppl 5):S213-S256.
- US Preventive Services Task Force. Final Update Summary: Lipid Disorders in Adults (Cholesterol, Dyslipidemia): Screening. Rockville, MD: US Preventive Services Task Force. http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lipid-disorders-in-adults-cholesterol-dyslipidemia-screening. Updated July 2015. Accessed August 11, 2016.
- Ned RM, Sijbrands EJG. Cascade screening for familial hypercholesterolemia (FH). PLoS Curr. 2011;3:RRN1238. doi:10.1371/currents.RRN1238.
- Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-3421.
- Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):S1-S45.
- Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):S49-S73.
- Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1—full report. J Clin Lipidol. 2015;9(2):129-169.
- Jacobson TA, Maki KC, Orringer CE, et al; NLA Expert Panel. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015;9(6):S1-S122.e1.
- Al-Rasadi K, Al-Waili K, Al-Sabti HA, et al. Criteria for diagnosis of familial hypercholesterolemia: a comprehensive analysis of the different guidelines, appraising their suitability in the Omani Arab population. Oman Med J. 2014;29(2):85-91.
- Brunzell JD. Clinical practice: hypertriglyceridemia. N Engl J Med. 2007;357(10):1009-1017.
- McLain JH, Alsterda AJ, Arora RR. Cholesteryl ester transfer protein inhibitors: trials and tribulations [published online August 10, 2016]. J Cardiovasc Pharmacol Ther. doi:10.1177/1074248416662349.