To The Editor
The American College of Cardiology/American Heart Association (ACC/AHA) guidelines for cholesterol treatment recommend statin therapy for individuals at elevated absolute cardiovascular disease (CVD) risk.1 This risk-based approach is a paradigm shift from prior Adult Treatment Panel (ATP) III guidelines which were heavily influenced by low-density lipoprotein (LDL) thresholds.2 A recent analysis estimated that the ACC/AHA guidelines will lead to a significant increase in statin use in the US, largely due to an increase in the eligibility of adults age >60 years without CVD or diabetes.3 The impact of the new guidelines on older individuals is important, as they are high risk for CVD but also may be prone to statin side effects.4 The aim of this study was to analyze the potential impact of the new guidelines and contemporary usage of statins in older black and white individuals in the Atherosclerosis Risk in Communities (ARIC) cohort using recent data.
Methods
We performed a cross-sectional analysis of black and white participants in ARIC who participated in the 5th study visit (2011-2013). ARIC is a longitudinal study of cardiovascular disease sponsored by the National Heart, Lung, and Blood Institute.5 Of the 10,036 ARIC participants who were alive through August 2013, 6,538 took part in visit 5 (response rate 65%). Of these, 6,088 (mean age 75.6 years [range 66 to 90]; 58.4% female) had sufficient data to be included in the study.
Medication use was verified by reviewing medications that participants brought to the visit. The prevalence of indications for statin therapy according to ACC/AHA guidelines and ATP III guidelines (which were the most relevant guidelines at the time of the ARIC visit 5), as well as use of statins and other lipid-lowering medications were analyzed.
Results
A considerable portion of the ARIC cohort was taking lipid-lowering therapy in 2011-13, but uncontrolled hyperlipidemia was still common by the ATP III guidelines then in place (Table 1). Individuals with a high absolute CHD risk (>20% 10-year) were the least likely to be at their LDL-C goal (49.2% not at goal) while participants with 0-1 CHD risk factors were most likely to be at goal (18.6% not at goal). Full implementation of the prior ATP III guidelines should have resulted in treatment of 72.8% of our sample.
Table 1.
Prevalence of hyperlipidemia and rates of control according to ATP III cholesterol guidelines in 6,088 participants from the 5th visit of the Atherosclerosis Risk in Communities Study, 2011-13.
| APT III CHD risk categories | |||||
|---|---|---|---|---|---|
| 0-1 Risk Factors | 2 Risk Factors | CHD risk >20% | Diabetics | Prevalent CHD | |
| LDL Goal | < 160mg/dL | < 130mg/dL | < 100mg/dL | < 100mg/dL | < 100mg/dL |
| N | 1521 | 1499 | 651 | 1566 | 851 |
| Age, years | 75.0 (5.0) | 74.4 (4.7) | 78.6 (5.0) | 75.2 (5.1) | 77.0 (5.2) |
| Female, % | 76.0 | 73.7 | 11.2 | 60.1 | 32.8 |
| African-American, % | 18.2 | 23.4 | 19.8 | 33.1 | 16.0 |
| LDL, mg/dL | 119.2 (32.8) | 108.0 (31.9) | 102.4 (31.2) | 97.0 (34.3) | 85.4 (33.8) |
| Not at LDL Goal, % | 18.6 | 25.6 | 49.2 | 41.6 | 26.0 |
| Any Statin % | 32.9 | 45.0 | 45.8 | 61.8 | 78.6 |
| HI Statin % | 2.2 | 5.3 | 4.0 | 9.5 | 25.6 |
| Other lipid medication, % | 3.9 | 4.7 | 4.5 | 5.5 | 4.9 |
| Any statin, not at goal, % | 9.0 | 11.0 | 28.5 | 25.7 | 16.0 |
| At goal, not on statin, % | 63.2 | 44.9 | 35.7 | 21.3 | 10.8 |
Full implementation of ATP III guidelines would result in treatment of 72.8% of the sample.
A total of 1,887 participants (31%) were not at LDL-C goal.
Of the 1,887 not at LDL goal, 560 (30%) were taking a statin.
Abbreviations: ATP Adult Treatment Panel, CHD – Coronary Heart Disease, LDL-C – Low-Density Lipoprotein Cholesterol, HI – High Intensity
In contrast, according to ACC/AHA guidelines, 97.0% of ARIC participants ≤ 75 years old met one of the 4 major indications for statin therapy (clinical CVD, diabetes, LDL cholesterol > 190mg/dL, or absolute 10-year CVD risk ≥ 7.5%, Table 2). Of these individuals ≤ 75 years old, 49.8% were taking a statin but only 9.0% were on a high-intensity statin (Table 2). Half the cohort studied was aged >75 years and 53.2% of these individuals were taking a statin. Individuals aged >75 years are not included in the AHA/ACC guidelines due to lack of evidence in this age group. These findings confirm that implementation of the new guidelines should significantly increase statin use in individuals age 65-75.
Table 2.
Frequency of eligibility for statin therapy according the ACC/AHA cholesterol guidelines and prevalences of statin and other lipid-lowering medication use in 6,088 participants from the 5th visit of the Atherosclerosis Risk in Communities Study, 2011-13.
| Statin Eligible Groups | |||||||
|---|---|---|---|---|---|---|---|
| Clinical CVD | Diabetes | LDL-C ≥190 | CVD risk ≥7.5% | All 4 Groups | CVD risk 5%-7.5% | CVD risk <5% | |
| N (%) | 1,823 (29.9%) | 1191 (19.6%) | 53 (0.8%) | 2,923 (48.0%) | 5,990 (98.4%) | 89 (1.5%) | 9 (0.1%) |
| Age, years | 76.9 (5.4) | 74.8 (4.9) | 73.6 (4.5) | 75.3 (4.9) | 75.7 (5.1) | 68.9 (1.3) | 67.7 (0.7) |
| Female, % | 48.7 | 59.0 | 75.5 | 62.2 | 57.7 | 100 | 100 |
| Race, % AA | 27.9 | 29.3 | 32.1 | 18.0 | 23.4 | 12.3 | 0 |
| Any Statin, % | 64.2 | 60.7 | 7.6 | 40.4 | 51.4 | 33.7 | 22.2 |
| HI Statin, % | 16.2 | 8.3 | 0 | 3.7 | 8.4 | 2.3 | 0 |
| Other LLM, % | 4.4 | 5.9 | 7.8 | 4.5 | 4.8 | 2.3 | 0 |
|
Age ≤75 years (n=3,315) | |||||||
| N (% of age group) | 799 (24.1%) | 722 (21.8%) | 39 (1.2%) | 1657 (50.0%) | 3217 (97.0%) | 89 (2.7%) | 9 (0.3%) |
| Any Statin, % | 62.6 | 59.6 | 7.7 | 40.4 | 49.8 | 33.7 | 22.2 |
| HI Statin, % | 20.2 | 8.5 | 0 | 4.1 | 9.0 | 2.3 | 0 |
|
Age >75 years (n=2,773) | |||||||
| N (% of age group) | 1024 (36.9%) | 469 (16.9%) | 14 (0.5%) | 1266 (45.7%) | 2773 (100%) | 0 | 0 |
| Any Statin, % | 65.4 | 62.5 | 7.1 | 40.4 | 53.2 | 0 | 0 |
| HI Statin, % | 13.2 | 8.1 | 0 | 3.2 | 7.7 | 0 | 0 |
The numbers in the categories for the 4 major indications were calculated successively from left to right. These categories are considered class 1 indications for statin therapy for individuals aged ≤75 years according to the ACC/AHA cholesterol guidelines.
The guidelines do not include individuals aged >75 years due to lack of evidence in this age group.
Abbreviations: ACC – American College of Cardiology, AHA – American Heart Association, CVD – Cardiovascular Disease, LDL – Low-Density Lipoprotein, AA – African American, HI – High Intensity, LLM – Lipid-lowering Medication.
Discussion
The increase in statin eligibility according to the new guidelines is largely due to the 7.5% CVD risk threshold in primary prevention. Although there is substantial evidence supporting a risk-based approach for statin allocation,1 the 7.5% CVD risk threshold is aggressive, creating a nearly universal recommendation for statin use in individuals age 65-75 years. The recently updated lipid guidelines in the United Kingdom have chosen a 10% CVD risk threshold for statin allocation.6 The ideal CVD risk threshold, the optimal role for statin therapy in the elderly, and the overall utility of statin therapy in primary prevention all remain highly controversial topics that require further research.
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. Journal of the American College of Cardiology. 2013 doi: 10.1016/j.jacc.2013.11.002. doi:10.1016/j.jacc.2013.11.002. [DOI] [PubMed] [Google Scholar]
- 2.National Cholesterol Education Program (NCEP) Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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;106:3143–421. [PubMed] [Google Scholar]
- 3.Pencina MJ, Navar-Boggan AM, D'Agostino RB, Sr, et al. Application of New Cholesterol Guidelines to a Population-Based Sample. N Engl J Med. 2014 Mar 19; doi: 10.1056/NEJMoa1315665. [Epub ahead of print] [DOI] [PubMed] [Google Scholar]
- 4.Pasternak RC, Smith SC, Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C, for the American College of Cardiology American Heart Association; National Heart, Lung and Blood Institute. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. Circulation. 2002;106:1024–1028. doi: 10.1161/01.cir.0000032466.44170.44. [DOI] [PubMed] [Google Scholar]
- 5.ARIC Investigators The atherosclerosis risk in the communities (ARIC) study: design and objectives. Am J Epidemiol. 1989;129:687–702. [PubMed] [Google Scholar]
- 6.NICE clinical guideline CG181 Lipid modification: Cardiovascular risk assessment of blood lipids for the primary and secondary prevention of cardiovascular disease. 2014 Jul; [PubMed] [Google Scholar]