Article Text

Download PDFPDF

Original research article
Residual cardiovascular risk in individuals on lipid-lowering treatment: quantifying absolute and relative risk in the community
  1. Wolfgang Lieb1,2,
  2. Danielle M Enserro1,3,4,
  3. Martin G Larson1,4 and
  4. Ramachandran S Vasan1,3,5
  1. 1 Framingham Heart Study, Framingham, Massachusetts, USA
  2. 2 Institute of Epidemiology, Christian Albrechts University Kiel, Kiel, Germany
  3. 3 Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, USA
  4. 4 Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA
  5. 5 Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA
  1. Correspondence to Dr Ramachandran S Vasan; vasan{at} and Dr Wolfgang Lieb; Wolfgang.lieb{at}


Objective The residual cardiovascular disease (CVD) risk in individuals on long-term lipid-lowering treatment (LLT) in the general population is not well described.

Methods We estimated absolute CVD risks by age and sex for different categories of low-density lipoprotein cholesterol (LDL-C) levels, stratified by LLT status, and assessed subclinical carotid atherosclerosis in 3012 Framingham Study participants (mean age, 58.4 years; 55% women) free of CVD. Individuals were categorised into five groups: (1) LDL-C <100 mg/dL without LLT; (2) LDL-C ≥100 mg/dL to <130 mg/dL without LLT; (3) LDL-C <130 mg/dL on LLT; (4) LDL-C ≥130 mg/dL without LLT; and (5) LDL-C ≥130 mg/dL on LLT.

Results Individuals in groups 3–5 had significantly more carotid atherosclerosis compared with group 1. During follow-up (median, 13.7 years), 548 CVD events occurred. Individuals on LLT (groups 3 and 5) had substantial residual CVD risk (26.7 (95% CI 19.5 to 34.0) and 24.1 (95% CI 16.2 to 31.9) per 1000 person-years, respectively), representing approximately three times the risk for untreated individuals with LDL <100 mg/dL (group 1: 9.0 (95% CI 6.8 to 11.3) per 1000 person-years). Absolute CVD risks rose with age and were slightly greater in men than in women. After adjustment for traditional risk factors, groups 3–5 displayed increased hazards for CVD (HR=1.47, 1.42 and 1.54, respectively) compared with group 1. Further adjustment for carotid atherosclerosis modestly attenuated these results.

Conclusions There is substantial residual CVD risk in individuals on LLT, compared with participants with optimal LDL-C (<100 mg/dL), even when LDL-C levels <130 mg/dL are reached.

  • LDL
  • cardiovascular disease
  • subclinical disease
  • lipids
  • residual risk

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

Statistics from


  • Contributors WL and RSV drafted the article. DME and MGL performed the statistical analyses. All authors interpreted the data and reviewed and edited the manuscript for important intellectual content.

  • Funding This work was supported by the Framingham core contract NO1-HC-25195 and HHSN268201500001I (to RSV).

  • Competing interests None declared.

  • Ethics approval The study protocol was approved by the Institutional Review Committee of Boston University Medical Center.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The data from the Framingham Heart Study used for this project are available in the NHLBI data repository BioLINCC ().

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.