Elsevier

Atherosclerosis

Volume 266, November 2017, Pages 24-30
Atherosclerosis

Familial hypercholesterolemia in primary care in Germany. Diabetes and cardiovascular risk evaluation: Targets and Essential Data for Commitment of Treatment (DETECT) study

https://doi.org/10.1016/j.atherosclerosis.2017.08.019Get rights and content

Highlights

  • FH has a higher than expected prevalence rate (1:300) in Germany.

  • FH maybe underdiagnosed in women under 50 years of age due to generally lower LDL-C levels in this age group.

  • The clinical diagnosis scores (DLCN, US-MEDPED) are not sufficient for a reliable diagnosis.

Abstract

Background and aims

Familial hypercholesterolemia (FH) is an inherited disorder of lipoprotein metabolism characterised by impaired removal of low-density lipoproteins (LDL) from the circulation, which leads to an increased risk of cardiovascular disease (CVD). This risk can be significantly lowered by early diagnosis and treatment. In Germany, reliable estimates of the prevalence of FH are lacking. We therefore examined the prevalence rate of FH in Germany in a primary care based cohort.

Method

We utilized records of 4722 participants in the DETECT study, in whom complete data on blood lipids and medical history were available. Prevalence rates were assessed using the Dutch Lipid Clinics Network (DLCN) and the US-MEDPED criteria. We stratified for gender and age. Group differences were analyzed using Chi2 and ANOVA tests.

Results

Using the DLCN (probable or definite FH) and the US.MEDPED criteria yielded prevalence rates of 1:278 and 1:295, respectively. The established diagnostic scores used in this analysis identify different patients. In women below 50 years of age, the LDL-C concentration is lower than in men, leading to the possibility of under-diagnosing FH in this group because women under the age of 50 are less likely to reach a higher DLCN-Score.

Conclusions

FH has a higher than expected prevalence in Germany. Clinical diagnostic algorithms may not be concordant.

Introduction

Familial hypercholesterolaemia (FH) is a monogenic lipometabolic disorder that results in increased LDL cholesterol (LDL-C) concentrations in the blood. It is associated with an increased risk of cardiovascular events. In men, the cumulative risk of cardiovascular events stands at 50% by the age of 50, and in women at 30% by the age of 60 years [1]. Cardiovascular diseases can, however, also occur in early adulthood [2]. Most frequently, FH is caused by mutations in the gene for the low density lipoprotein (LDL) receptor (approx. 90%) [3], [4], [5]. In addition to this, increased LDL concentrations in the blood may be attributable to mutations of the apolipoprotein (Apo) B100 [6], [7], the primary ligand of the LDL receptor or proprotein convertase subtilisin/kexin type 9 (PCSK9) [8], one of the regulators of the LDL receptor.

FH is inherited by way of autosomal dominance; In homozygous patients, the disease progresses very aggressively and at a more accelerated pace [9], [10]. Unfortunately, in many instances, FH is diagnosed and treated only after the occurrence of an initial cardiovascular event [11], [12]. This results in significantly compromised quality of life as well as avoidable, additional costs to the health care system (in-patient treatment, surgical interventions such as stent implants or bypass procedures, rehabilitation and medication).

The early identification of patients with FH makes it possible to initiate lipid-lowering therapy in a timely manner, thereby reducing the risk of cardiovascular disease and costs incurred by the health care system [13], [14]. FH is diagnosed on the basis of clinical characteristics, laboratory parameters and molecular-genetic testing. It is usually considered if the LDL-C is in excess of 4.9 mmol/L without treatment, if the patient presents with tendon xanthomas and/or arcus lipoides and/or if early-onset cardiovascular diseases or hypercholesterolaemia are evident in family [15]. There are currently a number of scoring systems for diagnosing FH on the basis of clinical criteria. The “Make Early Diagnosis to Prevent Early Deaths” (U.S. MEDPED) Score [16] and the Simon Broome criteria [17] are based on the LDL-C value and the family's medical history. The Dutch Lipid Clinic Network (DLCN) score also incorporates physical characteristics such as tendon xanthomas [18]. Simon Broome criteria and the DLCN score factor in the molecular-genetic detection of disease-specific mutations.

Hitherto, the prevalence rate of heterozygous FH in the general population has been pegged at 1:500; more recent estimates surmise higher prevalence ratios [2], [19], [20]. To date, there is no valid information specific to Germany [12]. This study aimed to determine the FH prevalence rate for the first time on the basis of clinical criteria and a cohort reflecting primary health care in Germany.

Section snippets

Study design and participants

The DETECT (Diabetes Cardiovascular Risk Evaluation: Targets and Essential Data for Commitment of Treatment) study is a multi-phase cross-sectional and longitudinal investigation representative of general physician (GP) care that enrolled 55,518 patients, who were examined in 3188 GP offices in 2003 [21]. The objectives and design of the DETECT study were described in detail by Wittchen et al. [21]. Recruitment of centres was based on a nation-wide sample of physicians with primary care

Prevalence of FH

The 4722 study participants examined were between 18 and 95 years of age, with the average age being 55.7 years (±14.3 years). 37.7% of the patients were male.

Of all patients, 54.3% had dyslipidemia according to the 2002 NECP definition [24]. Only 54.4% of the NCEP-classified patients with dyslipidemia were diagnosed as 'dyslipidemic' by their physicians (overall clinical diagnosis rate 29.5%). 27% of all patients with dyslipidemia (and 40.7% of the patients recognized as 'dyslipidemic' by

Discussion

The prevalence of FH in Europe is pegged at 1:200 to 1:2000, and has generally been assumed as 1:500 [2], [19], [25], [26]. In this study, we estimated the FH prevalence rate in the primary health care setting in Germany for the first time. This stands at close to 1:300, irrespective of whether the diagnosis is determined in accordance with the criteria of the DLCN Score or of the US-MEDPED Score. Thus, FH seems to occur more frequently in the general German population than previously assumed,

Conflict of interest

BS, AD, IG, JK, LP, HS, MK, DP, GS, HUW, TG declare no conflicts of interest. HL was part of the DETECT study board and received professional fee. WM is employed with Synlab Holding International GmbH. WM received professional fees for consultancy work and lectures and refund for travel expenses from Aegerion Pharmaceuticals, AMGEN GmbH, Sanofi Aventis GmbH and Synageva. WM is the principal investigator and NS the project coordinator of the German FH registry CaRe High, which is sponsored by

Financial support

The DETECT study was financed by unlimited research support provided by Pfizer, Karlsruhe. This evaluation was facilitated by unlimited research support provided by AMGEN GmbH, Munich to the D-A-CH-Gesellschaft Prävention von Herz-Kreislauferkrankungen e.V. (Regd Assocn).

Author contributions

NS wrote the manuscript draft and did the data analysis. BS provided epidemiological background and assisted on data analysis. HS provided the initial analysis routines for the data. AD, IG and MK were responsible for data preparation and management. LP and JK, as members of the DETECT study group, initially collected the data. HUW is the principal investigator of the DETECT study. HL and GS were members of the DETECT steering committee. DP and WM were members of the advisory board of the

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    DETECT (Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment) is a cross-sectional and prospective-longitudinal, nationwide clinical epidemiological study. DETECT has been supported by an unrestricted educational grant of Pfizer GmbH, Karlsruhe, Germany. Members of the DETECT-Study group include: Principal investigator: Professor Dr. H.-U. Wittchen; Staff members: Dr. L. Pieper, Dr. J. Klotsche, Dr. T. Eichler, Dr. H. Glaesmer, E. Katze. Steering Committee: Professor Dr. H. Lehnert (Lübeck), Professor Dr. G. K. Stalla (München), Professor Dr. A. M. Zeiher (Frankfurt); Advisory Board: Professor Dr. W. März (Mannheim/Graz), Professor Dr. S. Silber (München), Professor Dr. Dr. U. Koch-Gromus (Hamburg), Professor Dr. D. Pittrow (München/Dresden), Professor Dr. M. Wehling (Mannheim), Dr. D. Leistner (Frankfurt), Dr. H. J. Schneider (München), Dr. C. Sievers (München).

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