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Eradicating Atherosclerosis: Should We Start Statins at Younger Ages and at Lower LDL-Cs

  • Lipid Abnormalities and Cardiovascular Prevention (ED Michos, Section Editor)
  • Published:
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Abstract

Purpose of Review

Given the increasing burden of cardiovascular disease, we review the literature for earlier initiation of statin therapy at younger ages and lower low-density lipoprotein cholesterol (LDL-C) levels, with the goal of preventing the development of atherosclerosis prior to clinical events.

Recent Findings

There is a rising prevalence of dyslipidemia among younger adults. Although guidelines offer recommendations for adults over 40, there is little guidance for the management of younger adults with moderately elevated LDL-C levels. Earlier and more aggressive statin use may slow progression, or even halt atherosclerosis, and may likewise be beneficial and cost-effective on a population level.

Summary

Further research is needed to define the exact age and LDL-C level at which to start statin therapy. Until then, more detailed risk stratification with lab testing and imaging should be used to identify younger adults at the highest risk.

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References

Papers of particular interest, published recently, have been highlighted as: •   Of importance •• Of major importance

  1. Shah NS, Lloyd-Jones DM, Kandula NR, Huffman MD, Capewell S, O’flaherty M, Kershaw KN, Carnethon MR, Khan SS. Adverse trends in premature cardiometabolic mortality in the United States, 1999 to 2018. J Am Heart Assoc. 2020;9:18213.

    Article  Google Scholar 

  2. Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, Braunwald E, Sabatine MS. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA - J Am Med Assoc. 2016;316:1289–97.

    Article  CAS  Google Scholar 

  3. Thanassoulis G, Williams K, Ye K, Brook R, Couture P, Lawler PR, de Graaf J, Furberg CD, Sniderman A. Relations of change in plasma levels of LDL-C, non-HDL-C and apoB with risk reduction from statin therapy: a meta-analysis of randomized trials. J Am Heart Assoc. 2014. https://doi.org/10.1161/JAHA.113.000759.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation. 2019. https://doi.org/10.1161/CIR.0000000000000625.

    Article  PubMed  Google Scholar 

  5. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41:111–88.

    Article  PubMed  Google Scholar 

  6. Sniderman AD, Thanassoulis G, Williams K, Pencina M. Risk of premature cardiovascular disease vs the number of premature cardiovascular events. JAMA Cardiol. 2016;1:492–4.

    Article  PubMed  Google Scholar 

  7. World Health Organization. Noncommunicable diseases: risk factors. In: Glob Heal Obs. 2021. https://www.who.int/data/gho/data/themes/topics/indicator-groups/indicator-group-details/GHO/risk-factors.

  8. Center for Health Statistics N. Health, United States 2019: Table 23. Hyattsville, MD. 2019.

  9. Nguyen D, Kit B, Carroll M. Abnormal cholesterol among children and adolescents in the United States, 2011–2014. NCHS Data Brief. 2015:1–8.

  10. Carroll MD, Kruszon-Moran D, Tolliver E. Trends in apolipoprotein B, non-high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol for adults aged 20 and over, 2005–2016. Natl Health Stat Report. 2019.

  11. Arnett DK, Roger Blumenthal C-CS, Michelle Albert C-CA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2019;74:e177–232.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Jacobson TA, Maki KC, Orringer CE, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015;9:S1-S122.e1.

  13. 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;9:129–69.

    Article  PubMed  Google Scholar 

  14. •• Zeitouni M, Nanna MG, Sun JL, Chiswell K, Peterson ED, Navar AM. Performance of guideline recommendations for prevention of myocardial infarction in young adults. J Am Coll Cardiol. 2020;76:653–64. This was the first study to assess statin eligibility in younger patients with early ASCVD and found that fewer than half of patients younger than age 55 presenting with myocardial infarction were eligible for statin therapy per ACC/AHA guidelines.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Borén J, John Chapman M, Krauss RM, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2020;41:2313–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Domanski MJ, Tian X, Wu CO, et al. Time course of LDL cholesterol exposure and cardiovascular disease event risk. J Am Coll Cardiol. 2020;76:1507–16.

    Article  PubMed  CAS  Google Scholar 

  17. Abdullah SM, Defina LF, Leonard D, et al. Long-term association of low-density lipoprotein cholesterol with cardiovascular mortality in individuals at low 10-year risk of atherosclerotic cardiovascular disease: results from the Cooper Center Longitudinal Study. Circulation. 2018;138:2315–25.

    Article  PubMed  CAS  Google Scholar 

  18. • Zhang Y, Pletcher MJ, Vittinghoff E, et al. Association between cumulative low-density lipoprotein cholesterol exposure during young adulthood and middle age and risk of cardiovascular events. JAMA Cardiol. 2021;6:1406–13. This study found that LDL-C during young adulthood was associated with increased risk of future coronary artery disease independent of LDL-C during middle age.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Berenson GS, Wattigney WA, Tracy RE, Newman WP, Srinivasan SR, Webber LS, Dalferes ER, Strong JP. Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (the Bogalusa Heart Study). Am J Cardiol. 1992;70:851–8.

    Article  PubMed  CAS  Google Scholar 

  20. Enos WF, Holmes RH, Beyer J. Coronary disease among United States soldiers killed in action in Korea: preliminary report. J Am Med Assoc. 1953;152:1090–3.

    Article  PubMed  CAS  Google Scholar 

  21. • Javaid A, Mitchell JD, Villines TC. Predictors of coronary artery calcium and long-term risks of death, myocardial infarction, and stroke in young adults. J Am Heart Assoc. 2021. https://doi.org/10.1161/JAHA.121.022513. Results from this study demonstrated a strong and independent association with the presence of CAC in young adults and future ASCVD events, and found that when present, CAC was more predictive of ASCVD risk than traditional risk factors.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Loria CM, Liu K, Lewis CE, Hulley SB, Sidney S, Schreiner PJ, Williams OD, Bild DE, Detrano R. Early adult risk factor levels and subsequent coronary artery calcification. The CARDIA Study. J Am Coll Cardiol. 2007;49:2013–20.

    Article  PubMed  Google Scholar 

  23. Gidding SS, Rana JS, Prendergast C, et al. Pathobiological determinants of atherosclerosis in youth (PDAY) risk score in young adults predicts coronary artery and abdominal aorta calcium in middle age. Circulation. 2016;133:139–46.

    Article  PubMed  Google Scholar 

  24. Razavi AC, Bazzano LA, He J, Krousel-Wood M, Chen J, Fernandez C, Whelton SP, Kelly TN. Early contributors to healthy arterial aging versus premature atherosclerosis in young adults: the Bogalusa Heart Study. J Am Heart Assoc. 2021. https://doi.org/10.1161/JAHA.121.020774.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kiechl SJ, Staudt A, Stock K, et al. Predictors of carotid intima-media thickness progression in adolescents—the EVA-Tyrol study. J Am Heart Assoc. 2021. https://doi.org/10.1161/JAHA.120.020233.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Navar-Boggan AM, Peterson ED, D’Agostino RB, Neely B, Sniderman AD, Pencina MJ. Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease. Circulation. 2015;131:451–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Cohen JC, Boerwinkle E, Mosley TH, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354:1264–72.

    Article  PubMed  CAS  Google Scholar 

  28. Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, Kahn J, Afonso L, Williams KA, FlackJ M. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. Ration Pharmacother Cardiol. 2013;9:90–8.

    Article  Google Scholar 

  29. Ford I, Murray H, McCowan C, Packard CJ. Long-term safety and efficacy of lowering low-density lipoprotein cholesterol with statin therapy 20-year follow-up of west of Scotland coronary prevention study. Circulation. 2016;133:1073–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Sirtori CR. The pharmacology of statins. Pharmacol Res. 2014;88:3–11.

    Article  PubMed  CAS  Google Scholar 

  31. Mihaylova B, Emberson J, Blackwell L, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–90.

    Article  PubMed  CAS  Google Scholar 

  32. Rodenburg J, Vissers MN, Wiegman A, Van Trotsenburg ASP, Van Der Graaf A, De Groot E, Wijburg FA, Kastelein JJP, Hutten BA. Statin treatment in children with familial hypercholesterolemia: the younger, the better. Circulation. 2007;116:664–8.

    Article  PubMed  CAS  Google Scholar 

  33. Kusters DM, Avis HJ, De Groot E, Wijburg FA, Kastelein JJP, Wiegman A, Hutten BA. Ten-year follow-up after initiation of statin therapy in children with familial hypercholesterolemia. JAMA - J Am Med Assoc. 2014;312:1055–7.

    Article  CAS  Google Scholar 

  34. Klose G, Windler E, Nitschmann S. Efficacy and safety of statin therapy in children with familial hypercholesterolemia. Internist. 2019;60:878–80.

    Article  PubMed  CAS  Google Scholar 

  35. Nicholls SJ, Ballantyne CM, Barter PJ, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011;365:2078–87.

    Article  PubMed  CAS  Google Scholar 

  36. Koskinas KC, Siontis GCM, Piccolo R, Mavridis D, Räber L, Mach F, Windecker S. Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: a meta-analysis of randomized trials. Eur Heart J. 2018;39:1172–80.

    Article  PubMed  CAS  Google Scholar 

  37. Räber L, Ueki Y, Otsuka T, et al. Effect of alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infarction: the PACMAN-AMI randomized clinical trial. JAMA - J Am Med Assoc. 2022;327:1771–81.

    Article  CAS  Google Scholar 

  38. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713–22.

    Article  PubMed  CAS  Google Scholar 

  39. Zeb I, Li D, Nasir K, Malpeso J, Batool A, Flores F, Dailing C, Karlsberg RP, Budoff M. Effect of statin treatment on coronary plaque progression - a serial coronary CT angiography study. Atherosclerosis. 2013;231:198–204.

    Article  PubMed  CAS  Google Scholar 

  40. Hales CM, Fryar CD, Carroll MD, Freedman DS, Ogden CL. Trends in obesity and severe obesity prevalence in U.S. youth and adults by sex and age, 2007–2008 to 2015–2016. JAMA - J Am Med Assoc. 2018;319:1723–5.

    Article  Google Scholar 

  41. Yusuf PS, Hawken S, Ôunpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. Lancet. 2004;364:937–52.

    Article  PubMed  Google Scholar 

  42. Sawant AM, Shetty D, Mankeshwar R, Ashavaid TF. Prevalence of dyslipidemia in young adult Indian population. J Assoc Physicians India. 2008;56:99–102.

    PubMed  CAS  Google Scholar 

  43. Khera R, Valero-Elizondo J, Nasir K. Financial toxicity in atherosclerotic cardiovascular disease in the United States: current state and future directions. J Am Heart Assoc. 2020;9:1–10.

    Article  Google Scholar 

  44. • Kohli-Lynch CN, Bellows BK, Zhang Y, Spring B, Kazi DS, Pletcher MJ, Vittinghoff E, Allen NB, Moran AE. Cost-effectiveness of lipid-lowering treatments in young adults. J Am Coll Cardiol. 2021;78:1954–64. This was the first study to model the financial consequences of earlier statin initiation in young adults mith moderately elevated LDL-C and found statin therapy to be cost-effective in this population.

    Article  PubMed  CAS  Google Scholar 

  45. Harrington RA. Statins-almost 30 years of use in the United States and still not quite there. JAMA Cardiol. 2017;2:66.

    Article  PubMed  Google Scholar 

  46. Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388:2532–61.

    Article  PubMed  CAS  Google Scholar 

  47. Yang G, Sau C, Lai W, Cichon J, Li W. Pediatric markers of adult cardiovascular disease Micah. 2015;344:1173–8.

    Google Scholar 

  48. Vuorio A, Kuoppala J, Kovanen PT, Humphries SE, Tonstad S, Wiegman A, Drogari E, Ramaswami U. Statins for children with familial hypercholesterolemia. Cochrane Database Syst Rev. 2019. https://doi.org/10.1002/14651858.CD006401.pub5.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy - European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015;36:1012–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Wood FA, Howard JP, Finegold JA, et al. N-of-1 Trial of a statin, placebo, or no treatment to assess side effects. N Engl J Med. 2020;383:2182–4.

    Article  PubMed  Google Scholar 

  51. Mancini GBJ, Tashakkor AY, Baker S, et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian working group consensus update. Can J Cardiol. 2013;29:1553–68.

    Article  PubMed  Google Scholar 

  52. Mauricio R, Khera A. Statin use in pregnancy: is it time for a paradigm shift? Circulation. 2022;145:496–8.

    Article  PubMed  Google Scholar 

  53. United States Food and Drug Administration. FDA requests removal of strongest warning against using cholesterol-lowering statins during pregnancy; still advises most pregnant patients should stop taking statins. 2022. https://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-requests-removal-strongest-warning-against-using-cholesterol-lowering-statins-during-pregnancy#:~:text=On%20July%2020%2C%202021%2C%20FDA,they%20learn%20they%20are%20pregnant.

  54. Robinson JG, Williams KJ, Gidding S, et al. Eradicating the burden of atherosclerotic cardiovascular disease by lowering apolipoprotein b lipoproteins earlier in life. J Am Heart Assoc. 2018;7:1–12.

    Article  CAS  Google Scholar 

  55. Robinson JG, Davidson MH. Can we cure atherosclerosis? Rev Cardiovasc Med. 2018;19:S20–4.

    Article  PubMed  Google Scholar 

  56. Gidding SS, Robinson J. It is now time to focus on risk before age 40. J Am Coll Cardiol. 2019;74:342–5.

    Article  PubMed  Google Scholar 

  57. Pickar-Oliver A, Gersbach CA. The next generation of CRISPR–Cas technologies and applications. Nat Rev Mol Cell Biol. 2019;20:490–507.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Musunuru K, Chadwick AC, Mizoguchi T, et al. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature. 2021;593:429–34.

    Article  PubMed  CAS  Google Scholar 

  59. Verve Therapeutics. Verve therapeutics announces clearance of first VERVE-101 clinical trial application and outlines global clinical development strategy; Reports First Quarter Financial Results. 2022. https://www.globenewswire.com/en/news-release/2022/05/10/2439455/0/en/Verve-Therapeutics-Announces-Clearance-of-First-VERVE-101-Clinical-Trial-Application-and-Outlines-Global-Clinical-Development-Strategy-Reports-First-Quarter-2022-Financial-Results.html.

  60. Pencina MJ, Pencina KM, Lloyd-Jones D, Catapano AL, Thanassoulis G, Sniderman AD. The expected 30-year benefits of early versus delayed primary prevention of cardiovascular disease by lipid lowering. Circulation. 2020;827–837.

  61. Pencina MJ, D’Agostino RB, Larson MG, Massaro JM, Vasan RS. Predicting the 30-year risk of cardiovascular disease: the Framingham Heart Study. Circulation. 2009;119:3078–84.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Hussain A, Ballantyne CM, Nambi V. Zero coronary artery calcium score: desirable, but enough? Circulation. 2020;142:917–9.

    Article  PubMed  Google Scholar 

  63. Muhlestein JB, Knowlton KU, Le VT, et al. Coronary artery calcium versus pooled cohort equations score for primary prevention guidance: randomized feasibility trial. JACC Cardiovasc Imaging. 2022;15:843–55.

    Article  PubMed  Google Scholar 

  64. •• Mortensen MB, Gaur S, Frimmer A, et al. Association of age with the diagnostic value of coronary artery calcium score for ruling out coronary stenosis in symptomatic patients. JAMA Cardiol. 2022;7:36–44. This study demonstrated that the predictive capacity of CAC scoring varied by age, finding over half of patients younger than age 40 with symptomatic obstructive CAD had CAC = 0.

    Article  PubMed  Google Scholar 

  65. Dzaye O, Razavi AC, Dardari ZA, et al. Modeling the recommended age for initiating coronary artery calcium testing among at-risk young adults. J Am Coll Cardiol. 2021;78:1573–83.

    Article  PubMed  CAS  Google Scholar 

  66. Stone NJ, Smith SC, Orringer CE, et al. Managing atherosclerotic cardiovascular risk in young adults: JACC state-of-the-art review. J Am Coll Cardiol. 2022. https://doi.org/10.1016/j.jacc.2021.12.016.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69:692–711.

    Article  PubMed  CAS  Google Scholar 

  68. Wilson DP, Jacobson TA, Jones PH, Koschinsky ML, McNeal CJ, Nordestgaard BG, Orringer CE. Use of Lipoprotein(a) in clinical practice: a biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipidol. 2019;13:374–92.

    Article  PubMed  Google Scholar 

  69. Fernández-Ruiz I. AKCEA-APO(a)-LRx lowers Lp(a) levels in patients. Nat Rev Cardiol. 2020;17:132.

    PubMed  Google Scholar 

  70. Aragam KG, Natarajan P. Polygenic scores to assess atherosclerotic cardiovascular disease risk: clinical perspectives and basic implications. Circ Res. 2020;126:1159–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Natarajan P. Polygenic risk scoring for coronary heart disease: the first risk factor ∗. J Am Coll Cardiol. 2018;72:1894–7.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Raitakari O, Pahkala K, Magnussen CG. Prevention of atherosclerosis from childhood. Nat Rev Cardiol. 2022. https://doi.org/10.1038/s41569-021-00647-9.

    Article  PubMed  Google Scholar 

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Funding

Dr. Kelsey is supported by the National Institutes of Health (NIH) training grant 5T32HL069749-18.

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Authors and Affiliations

  1. Department of Medicine, Duke University, Durham, NC, USA

    Thomas O’Toole, Michelle D. Kelsey, Nishant P. Shah, Robert W. McGarrah & Neha J. Pagidipati

  2. Duke Clinical Research Institute, Durham, NC, USA

    Michelle D. Kelsey, Nishant P. Shah & Neha J. Pagidipati

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  1. Thomas O’Toole
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Correspondence to Thomas O’Toole.

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Conflict of Interest

Dr. Shah reports research grants from Amgen, Inc.; Janssen Pharmaceuticals; NIH; He also reports consulting fees from Amgen, Inc.; Novartis; Esperion. Dr. Pagidipati reports research grants from Amgen, Inc.; AstraZeneca; Baseline Study LLC; Boehringer Ingleheim; Duke Clinical Research Institute; Eggland’s Best; Eli Lilly & Company; Novartis Pharmaceuticals; Novo Nordisk Pharmaceutical Company; Sanofi-S.A.; Verily Sciences Research Company. She also reports consulting fees from AstraZeneca; Boehringer Ingleheim; Eli Lilly & Company; Novo Nordisk Pharmaceutical Company; Novartis. Drs. O’Toole and McGarrah have no disclosures to report.

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O’Toole, T., Kelsey, M.D., Shah, N.P. et al. Eradicating Atherosclerosis: Should We Start Statins at Younger Ages and at Lower LDL-Cs. Curr Cardiol Rep 24, 1397–1406 (2022). https://doi.org/10.1007/s11886-022-01760-y

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