Phenotypic characterization of patients with familial hypercholesterolemia

Boorsma, J.P. (Jan-Pieter) (2013) Phenotypic characterization of patients with familial hypercholesterolemia. thesis, Medicine.

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Abstract

Background: Autosomal dominant hypercholesterolemia (ADH) is known to be a major risk factor for cardiovascular disease (CVD), in particular coronary events. Familial hypercholesterolemia (FH) is the most common cause of ADH. This disorder is characterised by high levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). FH is the result of mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PSCK9). However, in a substantial proportion of patients with a clinical phenotype of FH no mutation can be detected. In the present study we assessed potential acquired causes of FH in FH mutation negative patients and evaluated the cardiovascular risk in patients and relatives with and without mutations. Methods: This retrospective study included 347 patients with a clinical phenotype of FH. All patients were outpatients from the University Medical Center Groningen (UMCG). Genetic analysis was performed in 337 patients, after informed consent. Patients lipid values, cardiovascular events, acquired causes of dyslipidemia, family history of CVD and hypercholesterolemia, and the results of the genetic tests were obtained using the digital patient database of the hospital. These data were compared between the patients with a FH related mutation (FH+) and the patients where no pathogen mutation could be identified (FH-). Results: In total there were 127 FH+ patients (37.7%) and 210 FH- patients (62.3%), while in 10 patients the genetic test results could not be retrieved. The mean age was 47.6 years. FH- patients were significantly older, and more frequently had hypertension. The prevalence of cardiovascular events, in particular myocardial infarction was higher in the FH- patients. While more family members of FH+ patients also had high cholesterol, more first-degree relatives with FH- had CVD. None of the acquired variables for FH significantly differed between FH- and FH+ patients. Many FH+ and FH- patients did not reach target LDL-C levels of <2.5 mmol/l with statins. Conclusions: No genetic mutation can be detected in 60% of the patients with clinical suspicion of FH. In these patients, no potential acquired cause of FH could be identified, which points to a possible polygenetic cause of high cholesterol levels. Interestingly, FH- patients and their first degree relatives were at higher risk of cardiovascular events, in particular myocardial infarction. Therefore, stringent cardiovascular control and treatment in FH- patients is as important as in FH+ patients.

Item Type:	Thesis (Thesis)
Supervisor name:	Supervisor: and Kamphuisen, Prof. dr. P.W. Internal/Vascular Medicine and Location: University Medical Center Groningen (UMCG), Vascul
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:45
Last Modified:	25 Jun 2020 10:45
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/676

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