Guest Editorial: New Guidelines Serve Diverse Populations Well

What will it take to lower your patient’s risk of heart attack and stroke? Can we improve on previous risk prediction tools? Can we address global cardiovascular disease risk better in women and African Americans? Can we initiate atherosclerotic cardiovascular disease (ASCVD) risk reduction with evidence based "proven" therapy? Finally, can we optimize the risk reduction obtained by a focus on adherence to both lifestyle and, in higher risk cases, the proper intensity of appropriate cholesterol lowering drug therapy? These are the challenges that the new AHA/ACC guidelines attempt to address.

The Risk Assessment Working Group designed a new risk calculator that improves on the Framingham Risk equation for “hard CHD” in ATP III in several important ways.¹ It uses pooled data from several long-standing, community-based US cohort studies. These new sex-specific and race-specific equations predict 10- year risk for atherosclerotic cardiovascular disease (ASCVD) and do an excellent job in rank ordering risk (from highest to lowest). Unlike the older Framingham risk scores, women and African Americans especially benefit. Now stroke is added as an outcome and African-American status as an input. For patients younger than age 60, lifetime risk can be estimated. We believe this is a superb aid for counseling patients on ASCVD risk reduction. Although there were accuracy concerns raised by some when the calculator was released, further review suggested that the problem might have been in the comparator groups chosen. These groups consisted of clinical trial candidates or participants with selfreported risk factors. They were not from long-standing community based cohorts such as those used to determine the risk equations. Indeed, it seems likely that the difference between observed and reported events in those predicted to be at higher risk by the calculator may represent statin use! This may be what occurred with participants of the Multi-ethnic Study of Atherosclerosis (MESA). MESA participants are not necessarily a sample representative of the greater US population as the cohort was selected from men and women 45-84 years of age, who were free of clinical ASCVD at entry Furthermore, MESA participants received their coronary calcium scores during the study which likely prompted preventive cardiovascular therapies, such as statins.²

Two examples of how the risk calculator works are given in Table 1.

This compares the same risk profile for an African American and non-African American woman. Her lipids are: TC 212, TG 140, HDL-C 47, LDL-C 137, non HDL-C 165. Non-HDL-C is in the risk equation because we enter total cholesterol and HDL-C.

The African American woman, age 62, with SBP 140, on no medication; without diabetes, not smoking, lipids: ASCVD risk 8.7%. The ACC AHA Guidelines suggest she should be offered the option of statin therapy considering the potential for benefit and adverse effects, drug-drug interactions and preferences. You explain to her that age represents a measure of the exposure to her risk factors. You note that she needs to follow either a DASH or a Mediterranean diet.

She is concerned about stroke (her mother had one in her 50s). We point out here that the guidelines discuss other factors that can be used when a risk decision is uncertain. These include family history of premature ASCVD, LDL-C ≥ 160 mg/dl, hs-CRP ≥ 2.0 mg/L, coronary calcium score ≥ 300 Agatston units; ankle brachial index (ABI) and a lifetime risk estimate. The guidelines indicate that before a statin prescription is written in primary prevention, a risk discussion occurs. You review potential for statin benefits, adverse effects and drug-drug interactions, control of other risk factors , and her preference. She inquires about diabetes risk with statin use. You point out that this risk is increased with age, female sex, but more importantly with blood sugar and obesity. You note her fasting blood sugar is 95 mg/ dl, her hemoglobin A1c is 5.5% and her BMI is 28.9.

She chooses both lifestyle change and a moderate intensity statin.

In 8 weeks when we see her back , we want to determine her adherence to both lifestyle and moderate intensity statin therapy. She is asked to come to the visit with a 3-day diet diary/exercise record and to have a lipid panel drawn before the visit. This will serve as a baseline for further adherence efforts. She wants to know if she should aim for a goal for her LDL-C levels. You point out that the new guidelines found strong evidence for intensity of statin therapy in groups shown to benefit from such therapy. ³

You expect, however, that she will likely attain an LDL-C <100 mg/dl based on both improved lifestyle and moderate intensity statin therapy. You specifically recommend a "system" such as a weekly pillbox next to the toothbrush as reminder for example so she won’t forget to take her statin.

You also have a risk discussion with a white woman, age 62, SBP 140 on no treatment, without diabetes and not smoking: Her ASCVD risk is 5.5%. She wants to know if she should take a statin to lower her LDL-C to less than 100 mg/ dl. You point out that under the new guidelines, the emphasis is on therapy whose benefits outweigh potential adverse effects. In those at lower global cardiovascular risk, the benefit/risk balance is not as favorable as when risk is higher. She has a family history of longevity but wants to be reassured that she doesn’t need a statin. You determine an hs-CRP which is 1.5. She reports improved lifestyle habits and will self-monitor with a diet diary, a pedometer, and daily weights. She is eager to see her progress and is scheduled to see your nurse for a BP check, weight, and lipid panel in 3 months.

Both of these cases emphasize that the guidelines are not "one size fits all." For high risk individuals such as those with ASCVD already, or diabetes in the 40-75 age range with LDL-C in the 70-189 mg/ dl range, or a primary elevation of LDL-C ≥ 190 mg/dl, the focus is on maximally tolerated statin intensity. For primary prevention, use of the risk calculator is designed to initiate a risk discussion to address the patient’s options. Whether a statin is used depends on numerous factors as described above and includes the patient’s preferences. Finally, other factors mentioned above can be helpful for the clinician-patient discussion.

For young adults, a family history of premature ASCVD or a primary elevation of LDL-C ≥ 160 mg/dl should prompt consideration of statin therapy despite the low 10-year ASCVD risk. For older adults, especially those 65-75 concerned that "age" alone is prompting a statin prescription, there is the potential to inform that decision with a coronary artery calcium score, hs-CRP, or ankle-brachial index. Physicians should find the safety section on statin therapy useful. Although non-statins are not drugs of first choice to lower ASCVD risk, the guidelines note they may be considered in higher risk patients (secondary prevention, primary elevation of LDL-C ≥ 190 mg/dl, and diabetes 40-75 years, LDL-C 70-<190 mg/ dl) who cannot tolerate maximal intensity of statin therapy or are completely statin intolerant.

These new guidelines focus on global cardiovascular risk assessment to determine those who are candidates for statin therapy. Statins were chosen as initial drugs of choice both to lower cholesterol and reduce ASCVD risk. Statins are both inexpensive (most are generic), and effective as shown in multiple, large-scale secondary and primary prevention clinical trials. Indeed, in primary prevention, both the per-person Cholesterol Treatment Trialists’ Meta- Analysis⁴ and the most recent Cochrane Review⁵ have shown that there is now evidence for reducing total mortality with statin therapy. The guidelines should focus therapy more precisely on those who will benefit the most.

As noted above, the cholesterol guideline mandated that the patient and clinician engage in a risk discussion before prescription of a statin occurs. This clinician-patient discussion was designed to understand the sources of the patient’s predicted risk, review potentially modifiable lifestyle factors that could help to reduce that risk, and provide a balanced perspective on the net gain from a statin prescription. This meant reviewing the potential for benefit as well as the potential for adverse effects or drug-drug interactions of statins. This is best appreciated by using an estimation of absolute risks as determined from randomized clinical trials.

Disclosure statement: Dr. Stone has no disclosures to report. Dr. Goldberg has received research grants from Abbott, Amarin, Merck, GlaxoSmithKline, ISIS, Genzyme, Sanofi, Regeneron, Genentech, Roche, Amgen and has received honorarium from Merck & Co., Inc. and Astra-Zeneca. Dr. Watson has received honorarium from Merck & Co. Inc.

References are listed on page 27.