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|Objective:||To quantify the risk for incident cardiovascular disease (CVD) events associated with different levels of low-density lipoprotein cholesterol (LDL-C) in a large community-based sample, stratified by the use of lipid lowering therapy (LLT). The study also aimed to assess the burden of subclinical disease at the carotid arteries in these individuals.|
|Study design:||Prospective analysis|
|Study population:||Individuals attending the sixth examination cycle of the Framingham Offspring cohort (1995–1998)|
Subjects were categorized according to one of five groups based on LDL-C levels and lipid lowering therapy:
- Group 1, LDL-C <100 mg/dL, not on LLT
- Group 2, LDL-C ≥100 mg/dL and <130 mg/dL, not on LLT
- Group 3, treated LDL-C <130 mg/dL on LLT
- Group 4, LDL-C ≥130 mg/dL, not on LLT
- Group 5, treated LDL-C ≥130 mg/dL on LLT
The 10-year probability of a CVD event was calculated according to each group; this was compared for treated versus untreated groups using analysis of variance.
Subclinical disease burden at the carotid arteries was analysed by LDL-C category using age-, sex- and multivariable-adjusted logistic regression models with group 1 (LDL-C <100 mg/dL, not on LLT) as the referrent. This model included age, sex, systolic blood pressure, antihypertensive medication, smoking and diabetes mellitus. The odds for ‘carotid ultrasound abnormality’ were compared for individuals on LLT versus untreated individuals using age-, sex- and multivariable-adjusted logistic regression models.
This analysis included data from 3,012 Framingham Study subjects (mean age, 58.4 years; 55% women) who were free of CVD at baseline (see Table 1).
Table 1. Categorization of subjects in the analysis (LDL-C in mg/dL)
LDL-C low-density lipoprotein cholesterol; LLT lipid-lowering therapy; SD standard deviation
Over a median of 13.7 years follow-up, 548 (255 women) developed an incident CVD event (Table 2).
Table 2. Incident CVD events and subclinical atherosclerosis (LDL-C in mg/dL)
|Authors’ conclusion:||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.|
There is indisputable evidence that LDL-C is causal for atherosclerotic CVD, and therefore guidelines for CVD prevention focus on LDL-C lowering therapeutic strategies as one of the key approaches for reducing cardiovascular risk.1-3 Statins, the first-line LDL-C lowering therapy, are efficacious in reducing cardiovascular risk.4 Yet even with attainment of guideline-recommended LDL-C levels, it is recognized that a substantial residual cardiovascular risk persists; this issue has been the ongoing focus of the Residual Risk Reduction Initiative.5
This study aimed to quantify the residual cardiovascular risk of individuals on long-term LLT, which has so far been poorly defined. The specific focus was on absolute cardiovascular risk in primary prevention individuals on LLT, both for those attaining LDL-C levels <130 mg/dL, and those with LDL?C above these levels. Absolute risk for incident CVD was about 3-fold higher in individuals on LLT (irrespective of LDL-C levels) than those with LDL-C levels <100 mg/dL who were not on treatment. Further analyses showed that this substantial residual cardiovascular risk may be partly explained by a worse cardiovascular risk factor profile; individuals in groups 3 and 5 (on LLT) had a higher prevalence of blood pressure lowering treatment (42-59% versus 16-24% in individuals not on LLT) and were also more likely to have diabetes (15-22% versus 6-7% in individuals not on LLT). Adjustment for subclinical carotid disease burden only moderately attenuated this residual cardiovascular risk.
In conclusion, these findings reaffirm the high residual cardiovascular risk that persists despite long-term LLT and attainment of guideline-recommended LDL-C goals. These findings underline the importance of a multifactorial approach to CVD prevention, considering both established and other risk factors to reduce this substantial residual cardiovascular risk.
1. Ference BA, Ginsberg HN, Graham I et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017;38:2459-2472.
2. Catapano AL, Graham I, De Backer G et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis 2016;253:281-344.
3. Piepoli MF, Hoes AW, Agewall S et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37:2315-2381.
4. Collins R, Reith C, Emberson J et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 2016;388:2532-2561.
5. Fruchart JC, Davignon J, Hermans MP et al. Residual macrovascular risk in 2013: what have we learned? Cardiovasc Diabetol 2014;13:26.
|Key words||residual cardiovascular risk; lipid lowering therapy; absolute risk; subclinical atherosclerosis|