CV Risk in Patients With FH on Optimal Therapy
Despite optimal treatment, how many patients with familial hypercholesterolemia (FH) will have a CV event, and which risk factors and patient factors are associated with a higher risk of these events?
A cohort of 821 patients with known FH on stable lipid-lowering therapy was analyzed for first and subsequent CV events as related multiple clinical characteristics using univariate and multivariate regression analysis.
In the study cohort of 821 FH lipid clinic patients on optimal or maximum tolerated lipid-lowering therapy, 102 or 12% of patients developed CV disease (CVD). Non-modifiable risk factors associated with a higher incidence of CVD event were a personal history of previous cardiac event (32 vs. 9%, p < 0.001) and a family history of CVD (58 vs. 40%, p = 0.001). Modifiable risk factors associated with a higher incidence of CVD event included hypertension (70 vs. 22%, p < 0.001), smoking (32 vs. 14%, p < 0.001), higher on-treatment low-density lipoprotein (LDL) (162 +/- 54 vs. 135 +/- 58 mg/dL, p < 0.001), and lower on-treatment high-density lipoprotein (HDL) (50 +/-15 vs. 54+/- 15 mg/dL, p < 0.001). Of the patients who had a CV event on lipid-lowering therapy, 30% had subsequent CV event; this was strongly associated with current smokers. In this cohort of patients, current smokers had a four-time greater risk of CV events, and patients with poorly controlled hypertension (defined as two or more blood pressures >140/90) had a three-times greater risk. In this population treated in a lipid specialty clinic, it is also important to note that only 19% reached an LDL cholesterol level of <100, leading to a higher risk of CV events. Use of PCSK9 inhibitors, given studies that show both a reduction in LDL cholesterol and reduction in CV events, may be appropriate in this high-risk group of patients for whom maximum tolerated lipid-lowering therapy has been insufficient.
Although treating dyslipidemia in patients with FH is an important aspect of lowering their overall risk of CV events, smoking cessation and optimal treatment of hypertension are key to reducing the risk of CV events. Treatment of LDL and HDL cholesterol to target levels with PCSK9 inhibitors may also reduce the risk of CV events in patients with FH.
Treating patients with FH for their dyslipidemia alone is not enough to lower their risk of CV events. Smoking and hypertension, as well as sub-target treatment of LDL cholesterol levels, all had a significant impact on the risk of CV events in these patients. Interestingly, only 4% of the cohort had diabetes, which may account for it having less of an effect. Also, despite expert specialty care in a lipid clinic, quite a few patients were not treated to goal LDL cholesterol levels. Overall, aggressive treatment of known CV risk factors for patients with FH and the addition of PCSKP inhibitors for the subset who do not reach targets on optimal lipid-lowering therapy may have a significant positive impact on their risk of future CV events.
Keywords: Hyperlipoproteinemia Type II, Cholesterol, LDL, Cholesterol, HDL, Dyslipidemias, Cardiovascular Diseases, Risk Factors, Smoking, Smoking Cessation, Hypertension, Blood Pressure, Proprotein Convertases
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