Lipid Guidelines: Update Balancing the New Guidelines With Naturopathic Practice

Jeremy Mikolai, ND

These guidelines have been widely criticized, as much or more for what they did not say as for the recommendations that were made. The 2013 ACC/AHA guidelines are statin-centric, they are low-density lipoprotein cholesterol (LDL-c)-centric, they completely change the initiation, management, and tracking of anti-lipid therapy, and they create indications for the use of HMG-CoA reductase inhibitors (statins) in about 13 million new patients.² Nowhere in these guidelines is any mention of dietary or lifestyle interventions.November of 2013 brought the long-awaited update to American guidelines on the management of lipids for the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD) in adults.¹ These are the first official updates to American practice guidelines since the publication of the Adult Treatment Panel – Three (ATP-3) updates in 2004. The 2013 guidelines were issued by the American College of Cardiology and American Heart Association (ACC/AHA) at the request of the National Heart Lung and Blood Institute (NHLBI). After many delays in ATP-4 consensus and publication, NHLBI asked ACC/AHA to take over the updating of practice guidelines for lipid management. They completed this project in only a few months and published the “2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults.”¹

The November 2013 ACC/AHA guideline updates were comprised of 4 separate statements: a guideline on cholesterol management; a new ASCVD risk calculator; a guideline on obesity; and another guideline on lifestyle recommendations. While important dietary and lifestyle aspects of the control of lipids and of ASCVD risk are acknowledged in the previous guidelines, the new lipids guideline document focuses specifically on the use of statin drugs.

2013 ACC/AHA Guidelines for Statin Selection

According to the 2013 ACC/AHA cholesterol guidelines, our approach to clinical lipid therapy should be to select the correct intensity of statin therapy that is appropriate for a patient, based on the patient’s 10-year and lifetime risks of of ASCVD, calculated with the new ASCVD risk calculator tool. This means no more numerical targets
(eg, under 100 mg/dL); rather, we are to select a particular intensity of statin therapy based on the patient’s group. There are 4 basic groups to consider:

patients who have had a previous ASCVD event;

patients who have an untreated LDL-c of 190 mg/dL or greater;

patients with known diabetes mellitus (DM); and

patients who have a calculated 10-year risk (based on the new ASCVD risk calculator) of greater than 7.5%.¹

Patients who fall into groups 1 or 2 are indicated for high-intensity statin therapy, whereas those in groups 3 or 4 are indicated for low-moderate statin therapy. Patients, however, who are in both groups 3 and 4 (DM and 10-year risk >7.5%), are indicated for high-intensity statin therapy.

The intensity of an individual statin therapy regimen is defined by the degree to which it can be expected to lower the untreated LDL-c level in an individual. High-intensity statin therapy (HIST), is defined by its ability to lower untreated LDL-c by greater than 50%. Low-moderate-intensity statin therapy (L-MIST) is defined by its ability to lower untreated LDL-c by 30-40%. There are only 4 statin drug regimens that meet the definition of HIST. Those 4 are easy to remember because they are simply the 2 most potent statin drugs at their 2 highest doses: rosuvastatin 40 mg and 20 mg, atorvastatin 80 mg and 40 mg. All other statin therapies are considered L-MIST.

ACC/AHA Rationale

The 2013 ACC/AHA guidelines have been criticized for being “statin-centric.” While this is true, it must be viewed in context. Statin drugs are the only anti-lipidemic agents which have a clear and demonstrable effect on ASCVD mortality. They prevent repeat ASCVD events in patients with known vascular disease (secondary prevention). For every 20 secondary prevention patients treated with statins for 5 years, 1 major vascular event (non-fatal myocardial infarction, coronary death, stroke, or the need for revascularization), will be prevented (NNT [number needed to treat]=20). In this same group, statin treatment of 77 people for 5 years would result in prevention of 1 death from any cause (NNT=77).³ In prevention of first ASCVD events (primary prevention), statin treatment of about 56 patients without vascular disease for 5 years will prevent 1 fatal or non-fatal myocardial infarction (NNT=56), which is a 27% risk reduction. Treatment of 96 primary prevention patients for 5 years will result in the prevention of 1 death from any cause (NNT=96) – a 14% risk reduction.⁴

Despite the ability of non-statin agents to lower lipids, their mortality benefits are unclear. Moreover, the policies of the ACC/AHA must be viewed in light of the larger goals of that institution toward public health. The goal of the AHA is a 20% reduction in deaths from CVD and strokes, and a 20% improvement in the cardiovascular health of all Americans by the year 2020; this is the so-called “AHA 20/20 Impact Goal.”⁵ Opponents of the new ACC/AHA lipid guidelines criticize that they create indications for more than 12 million new individual statin prescriptions; proponents espouse that if 12.8 million is the number of new indications, then 12.8 million is the correct number of new patients who should be on statins to lower the prevalence of CVD.²

It is relatively simple to see things from the ACC/AHA point of view, ipso facto, especially if we negate any personal prejudice against the use of statin drugs. However, even if we do so, at least 2 problems remain: 1) the risk-to-benefit ratio of statin treatment for primary prevention of events in patients without known ASCVD is less than perfectly clear, and 2) guidelines which prioritize evaluation and treatment of LDL-c are not directly in line with our present understanding of ASCVD risk.

National Lipid Association Response & Recommendations

The National Lipid Association (NLA) is a multidisciplinary specialty society comprised of over 3500 allied medical professionals and scientists whose mission is to enhance the practice of lipid management in clinical medicine.^6,7 In 2014, the NLA published the draft version of its “Recommendations for Patient-Centered Management of Dyslipidemia, Part 1.”⁹ The NLA is careful to point out that its considerations 1) are hastened as a result of the publication of the 2013 ACC/AHA lipid guidelines; 2) are still in keeping with the NLA’s strategic plan for a comprehensive set of lipid recommendations with yearly updates, on which it has been working for several years; 3) are not an alternative set of “guidelines” per se; rather they are “…intended to further inform clinical judgment regarding dyslipidemia management.”

2014 NLA Lipid Recommendations differ from 2013 ACC/AHA Cholesterol Guidelines in several important ways. First, 2014 NLA recommendations focus on “atherogenic cholesterol,” ie, all of those lipid species containing apolipoprotein B (Apo B), as the primary targets for therapeutic intervention, with an emphasis on non-HDL-c. Second, the NLA has maintained numerical targets for lipid modification and a risk scoring system for directing targets that is more similar to previous guidelines. Third, NLA recommendations support Apo B as a secondary target of therapy. Fourth, the NLA recommendations support the use of certain secondary testing for “risk refinement” beyond that discussed in ACC/AHA guidelines. Fifth, NLA recommendations emphasize the importance of lifestyle intervention in all patients with dyslipidemia, whether or not they are on drug therapy. Both ACC/AHA and the NLA support the importance of lifetime risk assessment in the management of ASCVD risk.

Why the NLA Recommendations Make Sense

The 2014 NLA recommendations’ emphasis on non-HDL-c is justified. The present body of evidence supports that Apo B-containing lipid particles are the root cause of atherosclerosis; that non-HDL-c has been demonstrated to be more predictive of ASCVD events than LDL-c; that when LDL-c and non-HDL-c levels are discordant, the latter is more closely associated with risk; that non-HDL-c is a universally available marker whose investigation incurs no additional cost and can be measured in the non-fasting state.⁸

According to 2014 NLA recommendations, patients are assigned appropriate targets for non-HDL-c and LDL-c levels according to risk assessment. In a manner similar to older guidelines, 2014 NLA recommendations begin with risk assessment of patients based on major risk factors and high-risk comorbidities, ultimately characterizing patients by qualitative risk: very high, high, moderate, or low risk. Low-to-high-risk individuals receive a target non-HDL-c of less than 130 mg/dL, and LDL-c of less than 100 mg/dL; very-high-risk individuals receive targets of less than 100 mg/dL for non-HDL-c, and of less than 70 mg/dL for LDL-c, respectively. These recommendations also address initiation of drug therapy based on qualitative risk and untreated lipid levels. Drug therapy is suggested when low, moderate, high and very-high-risk individuals exceed lipid levels of non-HDL-c (and LDL-c) of greater than: 190 (160), 160 (130), 130 (100) and 100 (70) mg/dL, respectively.⁸

The 2014 NLA recommendations endorse the use of Apo B as a secondary target of therapy. This is due to the fact that Apo B-containing particles are our most atherogenic lipid species and that occasionally patients meet non-HDL-c and LDL-c targets, yet maintain elevated Apo B levels. The recommendations are that Apo B levels be less than 90 mg/dL in primary prevention of ASCVD and less than
80 mg/dL in secondary prevention or very-high-risk individuals. Apo B levels are strongly correlated with ASCVD risk and are more predictive than LDL-c, but they have not been demonstrated to be consistently superior to non-HDL-c.⁸

Diverse Recommendations for Risk Refinement

Risk refinement is a topic of considerable concern in preventive cardiology. We understand that our risk prediction is imperfect, especially for those who fall into our “intermediate” risk categories. The ACC/AHA 2013 cholesterol guidelines dealt with this problem in
2 ways: first, they lowered the treatment threshold, ensuring the treatment of more at-risk individuals; second, they endorsed 3 tests for the further refinement of risk assessment in some individuals. Those tests are: blood levels of high-sensitivity C-reactive protein
(hs-CRP), ankle-brachial index measurement (ABI), and imaging by coronary artery calcium scoring (CACS).¹ By contrast, the 2014 NLA recommendations support risk refinement by: CACS, long-term ASCVD risk over 40%, hs-CRP over 2.0 mg/dL, Apo B over 120 mg/dL, LDL particle concentration greater than 1600 nmol/L, lipoprotein(a) greater than 50 mg/dL, urine albumin/creatinine ratio greater than 30 mg/g, or severe disturbance as a major risk factor (eg, profound family history, severely-elevated blood pressure, etc).⁸ Risk refinement may reveal elevated risk in individuals beyond traditional risk assessment and, as such, may change patient management and indications for therapy.

The 2014 NLA recommendations emphasize the importance of lifestyle interventions for all patients with dyslipidemia, whether or not they are on drug therapy, and issue an algorithmic approach to the escalation of interventions for treatment based on response to therapy. The NLA approach to therapy suggests that initiation of management should include lifestyle therapies: reduction of dietary saturated fat and cholesterol, moderate physical activity, weight loss if obese, and considerations for referral to a dietitian. Subsequent follow-up in 6 weeks should reassess lipid levels, re-emphasize initial recommendations, and intensify therapy if lipid goals have not been achieved. Intensification of therapy at the second visit should include considerations for: increased viscous fiber intake, the addition of plant sterols/stanols, and referral to a dietitian. Timeline to follow-up is another 6 weeks and includes laboratory reassessment of lipid levels. If targets are not met by the third visit, drug therapy should be initiated, with follow-up every 4-6 months to monitor adherence to lifestyle changes and consider reassessment of response to therapy. In the absence of contraindications, statin therapy (intensity as indicated by 2013 ACC/AHA guidelines), is considered the first-line drug therapy.⁸

Naturopathic Considerations

The practice of integrative and naturopathic medicine permits us some further refinement, considerations, and options in our redress of dyslipidemia and ASCVD risk. Many more interventions in the canon of the naturopathic physician are safe, effective, and available for the modification of lipids and can be initiated within the first 12 weeks of escalating therapies. Moreover, naturopathic approaches initiated early in the NLA approach algorithm may prevent or reduce much of the subsequent necessity for drug therapy. The NLA patient-centered approach to dyslipidemia management is completely synchronous with the naturopathic therapeutic order and its opinion about when drug therapy is indicated; it creates an excellent foundation for an integrative approach to ASCVD risk and prevention. When patients refuse pharmaceutical interventions despite appropriate recommendations, these guidelines offer us indispensable clarity on our goals and targets in the management of those patients and thresholds for when drug therapy must be recommended. The final versions of the NLA Recommendations on Patient-Centered Management of Dyslipidemia, parts 1 & 2, will be published in upcoming issues of the Journal of Clinical Lipidology.

Jeremy Mikolai, ND, graduated with highest honors from National College of Natural Medicine (NCNM) in Portland, OR, in 2010. He then completed 3 years of CNME-approved residency, including 1 year as Chief Resident for NCNM. He is presently a lead faculty member in the Heart & Lung Wellness Center of Excellence in Naturopathic Cardiovascular Medicine and assistant professor of Naturopathic Medicine at NCNM. He is also a professor of Cardiology in the naturopathic program at Universidad del Turabo in Gurabo, Puerto Rico, and co-founder and lead faculty member of the Naturopathic Institute of Cardiovascular and Pulmonary Medicine (NICVM).

References

1. Stone NJ, Robinson J, 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.
2. O’Riordan M. New guidelines extend statins to 13M more Americans. March 19, 2014. Medscape Web site. http://www.medscape.com/viewarticle/822210. Accessed June 15, 2014.
3. Minder CM, Blumenthal RS, Blaha MJ. Statins for primary prevention of cardiovascular of cardiovascular disease; the benefits outweigh the risks. Curr Opin Cardiol. 2013;28(5):554-560.
4. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;1:CD004816.
5. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics – 2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6-e245.
6. History of the National Lipid Association. The National Lipid Association Web site. http://www.lipid.org/about/history. Accessed June 15, 2014.
7. Mission of the National Lipid Association. National Lipid Association Web site. http://www.lipid.org/about/mission#. Accessed June 15, 2014.
8. Jacobson TA, Ito MK, Bays HE, et al. NLA Recommendations for Patient-Centered Management of Dyslipidemia, Part 1. [Monograph]. National Lipid Association Web site. http://www.lipid.org/patient-centered. Accessed June 15, 2014.