BackgroundUntreated patients with familial hypercholesterolemia are at increased risk of premature cardiovascular death. The primary aim of this study was to investigate whether this is also the case in the statin era.Methods and ResultsIn this registry‐based study, 4688 male and female patients from the Unit for Cardiac and Cardiovascular Genetics (UCCG) Registry with verified molecular genetic diagnosis of familial hypercholesterolemia in the period 1992–2010 were linked to the Norwegian Cause of Death Registry. Standardized mortality ratios and 95% CIs were estimated. There were 113 deaths. Mean age of death was 61.1 years. Cardiovascular disease was the most common cause of death (46.0%), followed by cancer (30.1%). Compared with the Norwegian population, cardiovascular disease mortality was significantly higher in the UCCG Registry in all age groups younger than 70 years (standardized mortality ratio 2.29, 95% CI 1.65 to 3.19 in men and women combined; standardized mortality ratio 2.00, 95% CI 1.32 to 3.04 in men; standardized mortality ratio 3.03, 95% CI 1.76 to 5.21 in women). No significant differences were found in all‐cause mortality or cancer mortality.ConclusionsDespite prescription of lipid‐lowering drugs, familial hypercholesterolemia patients still had significantly increased cardiovascular disease mortality compared with the general Norwegian population.

Cardiovascular disease is present in most FH patients at the time of death, underscoring the severity of FH and the need for early diagnosis and treatment.

ObjectiveThe primary objective was to study the risk of acute myocardial infarction (AMI) and coronary heart disease (CHD) in patients with familial hypercholesterolaemia (FH) and compare with the risk in the general population.MethodsPatients with an FH mutation but without prior AMI (n=3071) and without prior CHD (n=2795) were included in the study sample during 2001–2009. We obtained data on all AMI and CHD hospitalisations in Norway. We defined incident cases as first time hospitalisation or out-of-hospital death due to AMI or CHD. We estimated standardised incidence ratios (SIRs) with 95% CIs with indirect standardisation using incidence rates for the total Norwegian population stratified by sex, calendar year and 1 year age groups as reference rates.ResultsSIRs for AMI (95% CIs) were highest in the age group 25–39 years; 7.5 (3.7 to 14.9) in men and 13.6 (5.1 to 36.2) in women and decreased with age to 0.9 (0.4 to 2.1) in men and 1.8 (0.9 to 3.7) in women aged 70–79 years. Similarly, SIRs for CHD were highest among patients 25–39 years old; 11.1 (7.1–17.5) in men and 17.3 (9.6–31.2) in women and decreased 2.4 (1.4–4.2) in men and 3.2 (1.5–7.2) in women at age 70–79. For all age groups, combined SIRs for CHD were 4.2 (3.6–5.0) in men and 4.7 (3.9–5.7) in women.ConclusionPatients with FH are at severely increased risk of AMI and CHD compared with the general population. The highest excess risk was in the youngest group aged 25–39 years, in both sexes.

 714 adult FH subjects followed at a lipid clinic for 11.1 (7.9) years  LDL-C ≤2.5 mmol/L [~100 mg/dL] was achieved in 25% of FH subjects.  LDL-C ≤1.8 mmol/L [~70 mg/dL]) was achieved in 8% of very-high-risk FH subjects.  Prevalence of CHD was doubled in FH subjects with high Lp(a) levels.

Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have proved to reduce low density lipoprotein cholesterol levels in numerous clinical trials. In two large clinical trials PCSK9 inhibitor treatment reduced the risk of cardiovascular disease. Our aim was to explore the impact of varying assumptions about clinical effectiveness on health and economic outcomes for patients with familial hypercholesterolemia. Methods We used a previously published and validated Norwegian model for cardiovascular disease. The model was updated with recent data from the world's second largest registry of patients with genetically confirmed familial hypercholesterolemia. We performed analyses for 24 different subgroups of patients based on age, gender, statin tolerance and previous history of cardiovascular disease. Results In 1 out of 24 subgroups, PCSK9 inhibitors were cost-effective when effectiveness was modelled using direct relative efficacy as reported in the FOURIER trial. When using assumptions as suggested in a recent consensus statement from the European Atherosclerosis Society, 14 subgroups were cost-effective. Conclusion Cost-effectiveness of PCSK9 inhibitors depends highly on assumptions regarding effectiveness. Basing assumptions only on randomised controlled trials and not taking into account varying effect based on baseline cholesterol level results in much fewer groups being cost-effective.

Background Patients with familial hypercholesterolemia have increased cardiovascular disease mortality but the magnitude of the increased risk is uncertain. The primary aim of this study was to investigate all causes of death and place and manner of deaths in a large sample of genotyped familial hypercholesterolemia patients. Design, methods and results In this registry study data on 5518 patients with genotyped familial hypercholesterolemia were linked to the Norwegian Cause of Death Registry during 1992-2013. Standardized mortality ratios and 95% confidence intervals (CIs) were estimated. There were in total 189 deaths. Cardiovascular disease was the most common cause of death (42.3%). Mean age at cardiovascular disease death was 64.5 years (range 33-91). Cardiovascular disease mortality including all cardiovascular disease deaths mentioning any place on the death certificate was significantly higher in familial hypercholesterolemia patients compared to the general Norwegian population under 70 years of age. Standardized mortality ratio (95% CI) was highest in the 20-39 years age group; 4.12 (1.85-9.18) decreasing to 0.77 (0.50-1.19) for those over 80 years. For total cardiovascular disease deaths occurring out of hospital, standardized mortality ratio was 12.35 (5.14-29.70) for those aged 20-39 years. Conclusion Familial hypercholesterolemia patients under 70 years of age have significantly higher cardiovascular disease mortality compared to the general Norwegian population. For those aged 20-39 years the risk of cardiovascular disease deaths occurring out of hospital was increased 12-fold. In spite of genotyped familial hypercholesterolemia and premature cardiovascular disease deaths, the majority of all death certificates did not include familial hypercholesterolemia among any of the contributing causes of death.

ortic valve stenosis (AS) is the most common valvular disease in the western world. The underlying pathophysiology of AS is divided into an initiation phase resembling atherosclerosis, including lipid infiltration, oxidation, and inflammation, and a propagation phase characterized by fibrosis and calcification. 1 Even if low-density lipoprotein (LDL) cholesterol may be important in the initiation phase, lipid-lowering therapy with statins and ezetimibe has been unsuccessful in halting the disease. 2 Familial hypercholesterolemia (FH) is a disorder with increased levels of LDL cholesterol and increasing the risk of atherosclerotic diseases, particularly coronary heart disease. 3 In the severe homozygous form of FH, AS is seen frequently and more often in null mutations, with even higher LDL cholesterol than in defective mutations. 4 The risk of AS in heterozygous FH mutation carriers is not known. This study was de-signed as a prospective registry study to assess the risk of AS in a large cohort of genetically verified heterozygous patients with FH compared with the total Norwegian population. MethodsThe study was approved by the Regional Committee for Medical and Health Research Ethics, and the cohort, study design, and methods have been described previously. 3 In brief, this is a registry-based prospective cohort study of all genotyped patients with FH in Norway. Characteristics of 714 of 3161 patients in the FH cohort have been reported previously in a retrospective study on collection of data from medical records. 5 These patients had been followed up at a lipid clinic for a mean (SD) of 11.1 (7.9) years, and 89% of the patients were treated IMPORTANCE Aortic valve stenosis (AS) is the most common valve disease. Elevated levels of low-density lipoprotein (LDL) cholesterol are a risk factor; however, lipid-lowering treatment seems not to prevent progression of AS. The importance of LDL cholesterol in the development of AS thus remains unclear. People with familial hypercholesterolemia (FH) have elevated LDL cholesterol levels from birth and until lipid-lowering treatment starts. Thus, FH may serve as a model disease to study the importance of LDL cholesterol for the development of AS.OBJECTIVE To compare the incidence of AS per year in all genetically proven patients with FH in Norway with the incidence of these diseases in the total Norwegian population of about 5 million people. DESIGN, SETTING, AND PARTICIPANTS This is a registry-based prospective cohort study of all Norwegian patients with FH with regard to first-time AS between 2001 and 2009. All genotyped patients with FH in Norway were compared with the total Norwegian populations through linkage with the Cardiovascular Disease in Norway project and the Norwegian Cause of Death Registry regarding occurrence of first-time AS. Data were analyzed between January 1, 2018, and December 31, 2018. MAIN OUTCOMES AND MEASURES Standardized incidence ratios.RESULTS In total, 53 cases of AS occurred among 3161 persons (1473 men [46.6%]) with FH during 18 300 person-...

Background Familial hypercholesterolaemia increases the risk for cardiovascular disease. The primary aim of the present study was to describe sex differences in incidence and prevalence of cardiovascular disease leading to hospitalisation in a complete cohort of genotyped familial hypercholesterolaemia patients. Design and methods In this registry study data on 5538 patients with verified genotyped familial hypercholesterolaemia were linked to data on all Norwegian cardiovascular disease hospitalisations, and hospitalisations due to pre-eclampsia/eclampsia, congenital heart defects and diabetes. Results During 1994-2009 a total of 1411 of familial hypercholesterolaemia patients were hospitalised, and ischaemic heart disease was reported in 90% of them. Mean (SD) age at first hospitalisation and first re-hospitalisation was 45.1 (16.5) and 47.6 (16.3) years, respectively, with no sex differences ( P = 0.66 and P = 0.93, respectively). More men (26.9%) than women (24.1%) with familial hypercholesterolaemia were hospitalised ( P = 0.02). The median (25th-75th percentile) number of hospital admissions was four (two to seven) per familial hypercholesterolaemia patient, with no sex differences ( P = 0.87). Despite having familial hypercholesterolaemia at the time of hospitalisation, the diagnosis of familial hypercholesterolaemia was registered in only 45.7% of the patients at discharge. Conclusion Most cardiovascular disease hospitalisations were due to ischaemic heart disease. Familial hypercholesterolaemia patients were first time hospitalised at age 45.1 years, with no significant sex differences in age, which are important novel findings. The awareness and registration of the familial hypercholesterolaemia diagnosis during the hospital stays were disturbingly low.