Predicting Cardiovascular Events in Familial Hypercholesterolemia: The SAFEHEART Registry
Background—Although risk factors for atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia (FH) have been described, models for predicting incident ASCVD have not been reported. Our aim was to utilise the SAFEHEART registry to define key risk factors for predicting incident ASCVD in patients with FH.
Methods—SAFEHEART is a multicentre, nationwide, long-term prospective cohort study of a molecularly-defined population with FH, with or without previous ASCVD. Analysis to define risk factors and to build a risk prediction equation were developed and tested for its ability to discriminate patients who experience incident ASCVD from those who did not over time.
Results—We recruited 2404 adult patients with FH who were followed-up for a mean period 5.5 years (SD 3.2), during which 12 (0.5%) and 122 (5.1%) suffered fatal and non-fatal incident ASCVD respectively. Age, male gender, history of previous ASCVD, high blood pressure, increased body mass index, active smoking, and LDL-C and Lp(a) levels were independent predictors of incident ASCVD from which a risk equation (SAFEHEART-RE) with a Harrell's C index 0.85 was derived. The bootstrap resampling (100 randomized samples) of the original set for internal validation showed a degree of overoptimism of 0.003. Individual risk was estimated for each person without an established diagnosis of ASCVD before enrolment in the registry by using the SAFEHEART-RE, the modified Framingham's risk equation and the ACC/AHA ASCVD Pooled Cohort Risk Equations. Harrell's C index for these models were 0.81, 0.78 and 0.8 respectively and differences between the SAFEHEART-RE and the other two were significant (p=0.023 and p=0.045).
Conclusions—The risk of incident ASCVD may be estimated in FH patients using simple clinical predictors. This finding may improve risk stratification and could be utilized to guide therapy in patients with FH.
Clinical Trial Registration—https://clinicaltrials.gov Unique Identifier: NCT02693548
- familial hypercholesterolemia
- risk equation
- ischemic heart disease
- genetics, diagnostics
- risk assessment
- Received July 16, 2016.
- Revision received February 9, 2017.
- Accepted February 24, 2017.