Author | Study type | FH Population | Country | Outcomes | Results |
---|---|---|---|---|---|
Sivapalaratnam et al. 2010 [17] | 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 [20] | 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 [31] | 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 [32] | 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 [33] | 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 [34] | 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 [35] | 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 [36] | 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 [37] | 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 [38] | 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 [39] | 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 [40] | 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 [41] | 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 [42] | 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. |