|Author||Study type||FH Population||Country||Outcomes||Results|
|Sivapalaratnam et al. 2010 ||Observational study||40 FH patients||Netherlands Amsterdam||the effectiveness of statins on reducing the arterial wall thicknesses (cIMT)||
• Pre-treatment total cholesterol levels of FH patients were on average 9.3±2.0 mmol/L.|
• Pre-treatment, total cholesterol levels of FH patients were on average 9.3±2.0 mmol/L, whereas treated HF patients had LDL-C levels between 8±1.5 mmol/L and total cholesterol levels between 5.8±1.6.
• Long-term statin treatment reduced cIMT values in severe FH patients.
|Pérez de Isla et al. 2017 ||multicentre, nationwide, long-term prospective cohort study SAFEHEART||2404 adult patients with FH (molecularly defined population)||Spain Madrid||defining the key risk factors for predicting incident ASCVD||
• During the follow-up of the study (5.5 years), 122 patients (5.1%) suffered fatal and nonfatal incident ASCVD, respectively.|
• Age, male sex, history of previous ASCVD, high blood pressure, increased body mass index, active smoking, and low-density lipoprotein cholesterol and Lp(a) levels were independent predictors of incident ASCVD.
|Junyent et al. 2008 ||Case-control study||146 FH patients carrying null alleles (n=48), defective-receptor alleles (n=62), undetermined-function alleles (n=25), or APOB defects (n=11)||Spain, Barcelona||molecularly defined heterozygous FH in comparison with matched control subjects||
• 23 patients had coronary heart disease (CHD).|
• The frequency of both tendon xanthomas and CHD was 2-fold higher than in the control group.
• All femoral intima-media thickness (IMT) measurements were increased in FH patients versus patients in the control group (P=0.001).
• On multivariate analysis, the mean of IMT (a measure of early atherosclerosis) was independently associated with age, LDL-C, sex, and systolic blood pressure.
|Perak et al. 2016 ||6 large epidemiological cohorts||3850 (5.6%) had the FH phenotype by the primary definition (LDL-C levels ≥190 mg/dL and < 130 mg/dL)||USA, Chicago||coronary heart disease (CHD) total atherosclerotic cardiovascular disease (ASCVD) risks||
• After covariate adjustment, the FH phenotype was associated with high 30-year CHD risk (HR= 5, 95% CI: 1.1–21.7, P< 0.005).|
• CHD risk was increased by 10 to 20 years in men and 20 to 30 years in women.
• Total ASCVD risk was elevated (HR=4.1, 95% CI: 1.2–13.4, P< 0.005)
• FH phenotype definitions which included family history, LDL-C thresholds, or alternative lipid fractions, decreased the FH phenotype prevalence to 0.2–0.4%, without affecting the CHD risk (HR=8.0; 95% CI:1.0–61.6, P< 0.05).
|Pereira et al. 2015 ||observational cross-sectional study||202 patients with heterozygous FH||Brazil, São Paulo||association of peripheral artery disease PAD with other manifestations of cardiovascular disease (CVD)||
• The mean age was 51 ± 14 years, 35% men and total cholesterol levels were 342 ± 86 mg/dL.|
• The prevalence of PAD and previous CVD were 17 and 28.2%.
• On multivariate analysis, CVD was independently associated with the diagnosis of PAD (OR = 2.50; 95% CI: 1.004–6.230; P = 0.049).
|Nanchen et al. 2016 ||a multicentre, prospective cohort study||945 patients with clinical diagnosis of FH||Switzerland Lausanne||the occurrence of CV events during the first year after hospitalization for ACS||
• The prevalence of FH was 5.5% with the Simon Broome definition, and 1.6% with the Dutch Lipid Clinic score.|
• After multivariable adjustment including age, the risk was greater in patients with FH than in those without, with an adjusted HR =2.73 (95% CI: 1.46–5.11; P=0.002) for the Simon Broome definition and an adjusted HR =3.53 (95% CI: 1.26–9.94; P=0.017) for the Dutch Lipid Clinic definition.
• Patients with FH and ACS have a > 2-fold adjusted risk of coronary event recurrence within the first year after discharge than patients without FH despite the widespread use of high-intensity statins.
|Besseling et al. 2016 ||retrospective cohort study||1559 He FH patients||Netherlands Amsterdam||the relative risk reduction for CAD and for mortality by using statins||• In heterozygous (He) FH patients, the moderate - to high intensity statin therapy reduced the risk for CAD and the mortality by 44%.|
|Brunham et al. 2016 ||longitudinal observational study||339 patients with clinically diagnosed HeFH||Vancouver, Canada||characterizing the clinical features, the treatment patterns and CV outcomes||
• The overall CV event rate was 33.5/1000 person -years.|
• Among patients that had a CV event during the follow up, 59% experienced a recurrent event within 5 years.
• After using the lipid-lowering therapies, ≥50% reduction in LDL-C was achieved in 34.5% of the patients, and an LDL-C ≤2 mmol/L in 8.3%. Despite a majority of patients receiving lipid lowering therapy, few patients reached the lipid targets.
|Emanuelsson et al. 2018 ||prospective cohort study of the general population||7109 were diagnosed with FH||Denmark Copenhagen||establishing the PAD risk and the relationship between ABI and myocardial infarction||
• In multivariable adjusted ORs, PAD were 1.84 (95% CI: 1.70–2.00, P=0.001) in those with possible FH and 1.36 (95% CI: 1.00–1.84, P=0.001) in individuals with probable/definite FH compared with patients with unlikely FH.|
• The myocardial infarction was 4.60 (95% CI: 2.36–8.97, P=0.001) in those with possible/probable/definite FH and ABI< 0.9, compared with individuals with unlikely FH and ABI > 0.9.
|Faggiano et al. 2018 ||observational multicentre nationwide survey||368 with DLCN score> 3||Italy||evaluating the prevalence of potential FH and the therapeutic approaches among patients with established coronary artery disease (CAD) or PAD||
• The prevalence of potential FH was 3.7%.|
• Men represented 83.7% of the sample; the mean age was 65.9±10.6 years.
• The most common clinical presentation was new ACS, with or without percutaneous myocardial revascularization (52.5%), followed by stable CAD on medical therapy (26.5%); isolated lower extremity PAD was the least common presentation (3.1%).
• Definite FH (DLCN score> 8) had the highest percentages of patients after an ACS (75% vs 52.5% in the whole study population).
• At discharge, most patients were on high intensity statin therapy, they still had higher LDL-C levels, but without reaching the guideline’s goals.
|Petrov et al. 2018 ||observational study||196 patients with FH diagnosis||Bulgaria, Sofia||the examination of the clinical characteristics and the management of FH over a 12-month period||
• The mean age was 54.4 years, 64.1% of subjects were males.|
• Out of 196 patients the following number of patients met the criteria for FH diagnosis: 27 for definite FH, 94 for probable FH and 75 for possible FH.
• At baseline, the mean CV risk classification was 26.8% for CV high-risk and 73.2% for CV very high-risk.
• At enrolment, the LDL-C levels were 5.6 mmol/L and 4.1 mmol/L at the last observation visit (12 months).
• Most subjects (n=219) received statins, but without reaching the ESC/EAS defined LDL-C targets. Intensive statin treatment (atorvastatin 40–80 mg/daily and rosuvastatin 20–40 mg/daily) was used in 38.6% of the patients and 10% of the subjects received combined therapy (statin plus ezetimibe or other LLT). One subject was statin intolerant (ezetimibe therapy).
|Al-Rasadi et al. 2018 ||multicenter cohort (Gulf COAST cohort)||1030 patients with clinical FH||Arabian Gulf||assessing the prevalence of FH, its management, and impact on ASCVD||
• At admission, the proportion of “probable/definite”, “possible”, and “unlikely” FH in ACS patients was 3.7% (n =119), 28% (n=911), and 68% (n=2194).|
• The “probable/definite” FH group had a greater prevalence of early coronary disease (38% vs 8.8%; P< 0.001), and previous statin use (87% vs 57%; P < 0.001) compared with the “unlikely” FH group.
• After 1 year of follow-up, the “probable/definite” FH cohort had worse lipid control (13% vs 23%; P< 001) and presented a greater association with the composite ASCVD endpoint when compared with the “unlikely” FH group (OR=1.85; 95% CI: 1.01–3.38; P=0.047).
|Teramoto et al. 2018 ||retrospective observational study||3.495 FH patients 193 patients were existing diagnosis of FH (FH-D) and 3339 patients were suspected FH (FH-S)||Japan||evaluation of the epidemiology and the treatment patterns associated with lipid-modifying therapies||
• The mean LDL-C levels were 147.6 mg/dL for patients with FH-S and 119.2 mg/dL for FH-D.|
• 55.5% of the patients were treated with lipid-lowering therapy: high-intensity statins in 19.2% of the FH-D patients and 2.3% of the FH-S patients.
• Among the FH-D and FH-S statin treated patients, 69.3 and 89.7% respectively remained on monotherapy even when their LDL-C was ≥100 mg/dL.
• The therapy and management of LDL-C in Japanese FH patients remain suboptimal.
|Lalić et al. 2018 ||retrospective observational study||302 FH patients treated continuously with statins during 3 years||Serbia Belgrade||analyzing the effect of statin therapy on attainment of LDL-C treatment targets and appearance of new ASCVD and diabetes||
• The high intensity statin was prescribed in 17.9% of the cases.|
• LDL-C levels were significantly lower after 3 years of statin treatment (3.61 ± 1.19 mmol/l) vs. baseline (4.51 ± 1.69 mmol/l; P < 0.01)
• 6.9% of FH patients reached the recommended ≥50% LDL-C reduction and 16.2% attained the LDL-C < 2.6 mmol/l target.
• 9.6% of FH patients developed new ASCVD, with lower HDL-C levels after 3 years of statin treatment, as compared to those who remained free of ASCVD.