SAFEHEART risk-equation and cholesterol-year-score are powerful predictors of cardiovascular events in French patients with familial hypercholesterolemia

Gallo, Antonio; Charrière, Sybil; Vimont, A.; Chapman, M. John; Angoulvant, Denis; Boccara, Franck; Cariou, Bertrand; Carreau, Valérie; Carrié, Alain; Bruckert, Éric; Béliard, Sophie; Cottin, Yves; Filippo, Mathilde Di; Dulong, Sonia; Durlach, V.; Farnier, Michel; Ferrari, Émile; Ferrières, Dorota; Ferrières, Jean; Giral, Philippe; Gonbert, Sophie; Hankard, R.; Inamo, Jocelyn; Kalmykova, Olga; Krempf, Michel; Moulin, Philippe; Paillard, François; Peretti, Noël; Perrin, Agnès; Rabes, Jean Pierre; Sultan, Ariane; Tounian, P.; Valéro, René; Vergès, Bruno; Yelnik, Cécile; Ziegler, O.

doi:10.1016/j.atherosclerosis.2020.06.011

Cited by 35 publications

(26 citation statements)

References 33 publications

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“…Interestingly, the extent of LDL-C's effect on ASCVD is far greater in the Mendelian randomization studies than in the clinical trials; the primary underlying cause of this difference is considered to be life-long exposure to LDL-C. 20 Several studies have demonstrated that this hypothesis may be applicable to the general American population, 21,22 as well as to French patients with FH. 23 The present study lends strong support to this hypothesis in Japanese patients with FH, by additional consideration of the mutation status of FH genes and Achilles tendon thickness, clearly demonstrating that LDL-C is the causal factor for the development of ASCVD.…”

Section: Type Of Macessupporting

confidence: 77%

Effect of Cumulative Exposure to Low-Density Lipoprotein-Cholesterol on Cardiovascular Events in Patients With Familial Hypercholesterolemia

Tada

Okada

Nohara

et al. 2021

Circ J

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LDL-C levels throughout an individual's lifetime increase the risk; 5-8 however, validation studies using realworld data, especially those including patients with FH, are lacking. Conversely, we have recently reported that patients with FH identified through cascade screening at a younger age exhibit significantly better prognosis of ASCVD than their first relatives who seek medical attention at an older age. 9Therefore, we aimed to determine whether cholesterolyear-score, an indicator of cumulative exposure to LDL-C, was associated with ASCVD in Japanese patients with FH referred to Kanazawa University Hospital in Japan. Familial hypercholesterolemia (FH), caused primarily by mutations in the low-density lipoprotein (LDL) receptor (LDLR), proprotein convertase subtilisin/ kexin type 9 (PCSK9), or apolipoprotein B (APOB) genes, is characterized by the clinical triad of primary hyper-LDL cholesterolemia, tendon xanthomas, and premature atherosclerotic cardiovascular disease (ASCVD). 1,2 The prevalence of FH is ≈1 in 300 in general populations, 1 in 31 among individuals with ischemic heart disease, and 1 in 15 among those with premature ischemic heart disease. 3 Cumulative exposure to LDL-cholesterol (LDL-C) since birth is suggested to be detrimental in individuals with FH, leading to ASCVD beyond a certain threshold. 4 This cumulative exposure hypothesis has been widely accepted, based on the results of Mendelian randomization studies showing that particular genetic variations associated with Editorial p ????

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Section: Type Of Macessupporting

confidence: 77%

Effect of Cumulative Exposure to Low-Density Lipoprotein-Cholesterol on Cardiovascular Events in Patients With Familial Hypercholesterolemia

Tada

Okada

Nohara

et al. 2021

Circ J

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“…The LDL-C year score was calculated as follows: LDL-C year score (mg-year/dL) = LDL-C max (mg/dL) at diagnosis * age at diagnosis + LDL-C (mg/dL) at inclusion * [age at inclusion – age at diagnosis]. The total cholesterol year score was calculated as: total cholesterol year score (mg-year/dL) = TC max (mg/dL) at diagnosis * age at diagnosis + TC (mg/dL) at inclusion * [age at inclusion – age at diagnosis] [ 18 , 19 ].…”

Section: Methodsmentioning

confidence: 99%

Relations of physical signs to genotype, lipid and inflammatory markers, coronary stenosis or calcification, and outcomes in patients with heterozygous familial hypercholesterolemia

et al. 2021

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Background Although the presence of physical signs [tendon xanthomas and/or corneal arcus (TX/CA)], are associated with the risk of coronary artery disease in patients with heterozygous familial hypercholesterolemia (HeFH), their relationship with genotypes and clinical characteristics has not been fully determined. This study aimed to examine the association of TX/CA with genetic mutation, lipid- and inflammation-related markers, the severity of coronary stenosis or calcification, and cardiovascular events (CVEs) in patients with HeFH. Methods LDLR, APOB, and PCSK9 genes were screened in 523 HeFH patients, and patients with TX/CA (n = 50) were 1:4 propensity score-matched to patients without TX/CA (n = 200) to adjust for age and sex. Laboratory markers (proprotein convertase subtilisin/kexin type 9 [PCSK9], lipoprotein(a) and high-sensitivity C-reactive protein [hsCRP]), computed tomography angiography, coronary angiography, and follow-up for CVEs were performed. Results Patients with physical signs had significantly higher low-density lipoprotein cholesterol levels; higher PCSK9 or hsCRP concentrations; more LDLR positive mutations; and higher prevalence of high tertiles of Gensini, SYNTAX and Jeopardy scores as well as coronary artery calcium scores than did those without. Over an average follow-up of 3.7 years, the incidence of CVEs was significantly higher in patients with TX/CA (log-rank p < 0.001). Patients with physical signs and mutation positivity had threefold higher risks of CVEs (adjusted hazard ratio 3.34, 95% confidence interval 1.04–10.72, p = 0.024). Conclusions Physical signs were associated with genotypes and phenotypes, and worse outcomes in patients with HeFH, suggesting that these signs may help in risk stratification in these patients.

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“…High intensity statin dose was defined as previously described (atorvastatin 40 or 80 mg/day, rosuvastatin 20 or 40 mg/day, or simvastatin 80 mg/day) [13] .…”

Section: Methodsmentioning

confidence: 99%

Myocardial fibrosis assessed by magnetic resonance imaging in asymptomatic heterozygous familial hypercholesterolemia: the cholcoeur study

Giral¹,

Rosenbaum²,

Mattina³

et al. 2021

eBioMedicine

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Background Familial Hypercholesterolemia (FH) is an underdiagnosed condition with an increased cardiovascular risk. It is unknown whether lipid accumulation plays a role in structural myocardial changes. Cardiovascular Magnetic Resonance (CMR) is the reference technique for the morpho-functional evaluation of heart chambers through cine sequences and for myocardial tissue characterization through late gadolinium enhancement (LGE) and T1 mapping images. We aimed to assess the prevalence of myocardial fibrosis in FH patients. Methods Seventy-two asymptomatic subjects with genetically confirmed FH (mean age 49·24, range 40 to 60 years) were prospectively recruited along with 31 controls without dyslipidaemia matched for age, sex, BMI, and other cardiovascular risk factors. All underwent CMR including cine, LGE, pre- and post-contrast T1 mapping. Extracellular volume (ECV) and enhancement rate of the myocardium (ERM = difference between pre- and post-contrast myocardial T1, normalized by pre-contrast myocardial T1) were calculated. Findings Five FH patients and none of the controls had intramyocardial LGE (p= 0·188). While no changes in Native T1 and ECV were found, post-contrast T1 was significantly lower (430·6 ± 55ms vs. 476·1 ± 43ms, p<0·001) and ERM was higher (57·44± 5·99 % vs 53·04±4·88, p=0·005) in HeFH patients compared to controls. Moreover, low post-contrast T1 was independently associated with the presence of xanthoma (HR 5·221 [1·04-26·28], p= 0·045). A composite score combining the presence of LGE, high native T1 and high ERM (defined as ≥ mean ± 1·5 SD) was found in 20·8% of the HeFH patients vs. 0% in controls (p<0·000, after adjustment for main confounders). Interpretation CMR revealed early changes in myocardial tissue characteristics in HeFH patients, that should foster further work to better understand and prevent the underlying pathophysiological processes.

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SAFEHEART risk-equation and cholesterol-year-score are powerful predictors of cardiovascular events in French patients with familial hypercholesterolemia

Abstract: SAFEHEART-risk equation can now be used in other European population of HeFH patients to predict CV events.• The cholesterol-year-score is a robust predictor of CV events in HeFH patients.• SAFEHEART-RE and the cholesterol-year-score are valid in primary prevention heFH patients.

Cited by 35 publications

References 33 publications

Effect of Cumulative Exposure to Low-Density Lipoprotein-Cholesterol on Cardiovascular Events in Patients With Familial Hypercholesterolemia

Effect of Cumulative Exposure to Low-Density Lipoprotein-Cholesterol on Cardiovascular Events in Patients With Familial Hypercholesterolemia

Relations of physical signs to genotype, lipid and inflammatory markers, coronary stenosis or calcification, and outcomes in patients with heterozygous familial hypercholesterolemia

Myocardial fibrosis assessed by magnetic resonance imaging in asymptomatic heterozygous familial hypercholesterolemia: the cholcoeur study

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