Lastly, CCTA has also been shown to help risk stratify asymptomatic patients with FH. Patients with higher vaFRS demonstrated markedly elevated CVD risk: all 15 subjects who suffered ASCVD events had a vaFRS>20%. 21 Additionally, these same investigators calculated a vascular age with the standard Framingham Risk. In adjusted models, CAC was found to be an independent predictor of ASCVD events. Higher CAC scores correlated with an increased incidence of major adverse cardiovascular events. Among patients with a CAC score of 0 (n= 101, 49%), no ASCVD events were observed. 20 In a prospective study by Miname et al, 206 asymptomatic molecularly confirmed individuals with heterozygous FH were followed for a median of 3.7 years to evaluate CAC as a predictor of ASCVD events. Given robust improvements in discrimination, calibration, and net reclassification in the general population, CAC scoring has been evaluated in FH populations for further ASCVD risk stratification. 17 Despite this observation, cIMT has not been shown to correlate with vascular disease in the aorta or coronaries in FH patients. 16 Indeed, pediatric FH patients who were started on statins and followed over 20 years had decreased progression of cIMT and fewer cardiovascular events in comparison to their parents. With respect to cIMT, pediatric FH patients have higher cIMT values as compared to age-matched controls with normal lipid levels, suggesting utility as a non-invasive marker of ASCVD risk. Imaging modalities that have been studied in patients with FH include carotid intima-media thickness (cIMT), coronary artery calcium (CAC) scoring, and coronary computed tomography angiography (CCTA). 15 However, within the context of FH, the utility of atherosclerosis imaging is to identify individuals who may be eligible for more aggressive management approaches above and beyond therapeutic lifestyle changes and statin therapy. All adult patients with FH should receive lifestyle counseling and high intensity statin therapy independent of additional testing statin therapy should be started at the lowest dose in children and titrated upwards. It is important to clarify that the role of atherosclerosis imaging in FH is quite different than its routine use in the general population. Potential advantages of genetic testing include formal confirmation of a diagnosis of FH as well as the ability to facilitate cascade genetic screening.Īlthough there are many putative clinical and laboratory markers that can provide incremental prognostic information, refining risk stratification with measures of subclinical coronary atherosclerosis in asymptomatic FH individuals appears to be the most promising. 13 Additional challenges of genetic testing include genetic discrimination for possible life and long-term care insurance. This observation may be explained due to mutations in established genes that have yet to be discovered, novel FH genes, or presence of an FH phenocopy. Individuals with a clinical diagnosis of definite FH are found to harbor causal mutations only 60-80% of the time. There are important caveats in the molecular diagnosis of FH. 4,8 This risk can be reduced to that of the general population with appropriate recognition and treatment of FH. 4 Patients with untreated heterozygous FH are at approximately 10-20-fold increased risk for premature coronary artery disease (CAD). Although the prevalence of FH in the general population is substantial, only about 15% to 20% of affected patients receive a formal diagnosis. The fundamental pathophysiologic hallmark of FH is accelerated atherosclerosis due to the cumulative lifetime exposure to high concentrations of circulating LDL. 4-7 There are three major genetic loci linked to FH, with the majority (approximately 88%) of cases due to mutations in the LDL receptor ( LDLR) gene. 1-3 FH is caused by inherited autosomal-dominant defects of LDL metabolism ( Table 1). What are some important considerations in the management of this patient?įamilial Hypercholesterolemia: Prevalence and Pathophysiology, and Screeningįamilial hypercholesterolemia (FH) is the most common monogenic disorder, affecting an estimated 1:250 people worldwide. Labs are notable for a calculated low-density lipoprotein (LDL)-cholesterol (LDL-C) of 284 mg/dL. Physical exam is unremarkable apart from a body-mass index of 33 kg/m 2. He is asymptomatic but reports that he has first-degree relatives with a history of coronary artery disease, some of whom required coronary artery bypass surgery in their fourth decade of life. A 44-year-old male presents to your clinic to establish care.
0 Comments
Leave a Reply. |