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1.
Eur J Clin Nutr ; 73(12): 1622-1625, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31695140

RESUMO

The association of components of a low saturated fat (SFA) and of a Mediterranean diet was tested with atherosclerosis biomarkers in 190 familial hypercholesterolemia adults (FH) from Brazil (BR) and Spain (SP). Median blood LDL-C, Apolipoprotein B (apoB), and C reactive protein (hs-CRP) concentrations were higher in BR than in SP: 179.0 vs.161 mg/dL; 141 vs. 103 mg/dL; and 1.6 vs. 0.8 mg/L respectively (all p < 0.001). In BR there was lower median total fat (22.3 vs. 38.3%) and SFA (8.1 vs. 12.5%) but higher cholesterol (283.3 mg vs.188.9 mg) and carbohydrate (57.1 vs. 42.5%) consumption (all p < 0.001). Inverse associations were encountered between fibers, mono, and polyunsaturated fats and their ratios to SFA with LDL-C and ApoB (all p < 0.001). There was a direct association respectively of cholesterol with lipid biomarkers and of carbohydrates and trans-fatty acids with hs-CRP while other fats showed inverse relations with the latter (p < 0.001).

2.
Prog Cardiovasc Dis ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669498

RESUMO

Familial hypercholesterolemia (FH) is a frequent genetic disorder characterized by elevated low-density lipoprotein (LDL)-cholesterol (LDL-C) levels and early onset of atherosclerotic cardiovascular disease. FH is caused by mutations in genes that regulate LDL catabolism, mainly the LDL receptor (LDLR), apolipoprotein B (APOB) and gain of function of proprotein convertase subtilisin kexin type 9 (PCSK9). However, the phenotype may be encountered in individuals not carrying the latter monogenic defects, in approximately 20% of these effects of polygenes predominate, and in many individuals no molecular defects are encountered at all. These so-called FH phenocopy individuals have an elevated atherosclerotic cardiovascular disease risk in comparison with normolipidemic individuals but this risk is lower than in those with monogenic disease. Individuals with FH are exposed to elevated LDL-C levels since birth and this explains the high cardiovascular, mainly coronary heart disease, burden of these subjects. However, recent studies show that this risk is heterogenous and depends not only on high LDL-C levels but also on presence of previous cardiovascular disease, a monogenic cause, male sex, smoking, hypertension, diabetes, low HDL-cholesterol, obesity and elevated lipoprotein(a). This heterogeneity in risk can be captured by risk equations like one from the SAFEHEART cohort and by detection of subclinical coronary atherosclerosis. High dose high potency statins are the main stain for LDL-C lowering in FH, however, in most situations these medications are not powered enough to reduce cholesterol to adequate levels. Ezetimibe and PCSK9 inhibitors should also be used in order to better treat LDL-C in FH patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31702778

RESUMO

AIMS: The objective of this study was to evaluate if vascular age derived from coronary artery calcium (CAC) score improves atherosclerosis cardiovascular disease (ASCVD) risk discrimination in primary prevention asymptomatic heterozygous familial hypercholesterolaemia (FH) patients undergoing standard lipid-lowering therapy. METHODS AND RESULTS: Two hundred and six molecularly confirmed FH individuals (age 45 ± 14 years, 36% males, baseline LDL-cholesterol 6.2 ± 2.2 mmol/L; 239 ± 85mg/dL) were followed by 4.4 ± 2.9 years (median: 3.7 years, interquartile ranges 2.7-6.8). CAC measurement was performed, and lipid-lowering therapy was optimized according to FH guidelines. Vascular age was derived from CAC and calculated according to the Multi Ethnic Study of Atherosclerosis algorithm. Risk estimation based on the Framingham equations was calculated for both biological (bFRS) and vascular (vaFRS) age. During follow-up, 15 ASCVD events (7.2%) were documented. The annualized rate of events for bFRS <10%, 10-20%, and >20% was respectively: 8.45 [95% confidence interval (CI) 3.17-22.52], 23.28 (95% CI 9.69-55.94), and 28.13 (95% CI 12.63-62.61) per 1000 patients. The annualized rate of events for vaFRS <10%, 10-20%, and >20% was respectively: 0, 0, and 50.37 (95% CI 30.37-83.56) per 1000 patients. vaFRS presented a better discrimination for ASCVD events compared to bFRS 0.7058 (95% CI 0.5866-0.8250) vs. vaFRS 0.8820 (95% CI 0.8286-0.9355), P = 0.0005. CONCLUSION: CAC derived vascular age can improve ASCVD risk discrimination in primary prevention FH subjects. This tool may help further stratify risk in FH patients already receiving lipid-lowering medication who might be candidates for further treatment with newer therapies.

4.
Curr Atheroscler Rep ; 21(12): 48, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31741187

RESUMO

PURPOSE OF REVIEW: The goal of this review is to evaluate the role of inhibiting the synthesis of lipoproteins when there is no or little residual LDL-receptor function as in patients with homozygous familial hypercholesterolaemia. Lomitapide is administered orally once a day while mipomersen is given by subcutaneous injection once a week. Lomitapide inhibits microsomal triglyceride transfer protein while mipomersen is an antisense oligonucleotide directed against apoB100. RECENT FINDINGS: The pivotal registration trials for lomitapide and mipomersen were published in 2013 and 2010, respectively. More recently published data from extension trials and cohort studies provides additional information on long-term safety and efficacy. The mean LDL cholesterol reduction was 50% with lomitapide in its single-arm open-label registration trial. Mipomersen reduced LDL cholesterol by approximately 25% in its double-blind, placebo-controlled registration study. Both lomitapide and mipomersen therapy are associated with variable increases in hepatic fat content. The long-term safety of increased hepatic fat content in patients receiving these therapies is uncertain and requires further study. Both drugs may cause elevated transaminase in some patients, but no cases of severe liver injury have been reported. Lomitapide may also cause gastrointestinal discomfort and diarrhoea, especially if patients consume high-fat meals and patients are advised to follow a low-fat diet supplemented with essential fatty acids and fat-soluble vitamins. Mipomersen may cause injection-site and influenza-like reactions. The effect of lomitapide and mipomersen on cardiovascular outcomes has not been studied, but circumstantial evidence suggests that the LDL cholesterol lowering achieved with these two agents may reduce cardiovascular event rates.

5.
Arch Med Res ; 50(6): 362-367, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31678894

RESUMO

BACKGROUND: Although elevated high-density lipoprotein cholesterol (HDL-C) is considered protective against atherosclerotic cardiovascular disease, no causal relationship has been demonstrated. HDL-C comprises a group of different subfractions that might have different effects on atherosclerosis. Our objective was to investigate the association between HDL-C subfractions with the coronary artery calcium (CAC) score. METHODS: We included 3,674 (49.8 ± 8.3 years, 54% women) participants from the ELSA-Brasil study who had no prior history of CVD and were not currently using lipid-lowering medications. We measured the fasting lipoprotein cholesterol fractions (in mmol/l) by a zonal ultracentrifugation method (VAP). We analyzed the independent predictive values of total HDL-C, HDL2-C, and HDL3-C subfractions and in the HDL2-C/HDL3-C ratio using linear regression to predict Ln(CAC+1) and logistic regression to predict the presence of CAC. RESULTS: Overall 912 (24.8%) of the participants had CAC>0, and 294 (7.7%) had CAC>100. The mean total HDL-C, HDL2-C, and HDL3-C were: 1.42 ± 0.37, 0.38 ± 0.17 and 1.03 ± 0.21 mmol/l, respectively. Individuals with CAC>0 had lower levels of total HDL-C as well as of each subfraction (p < 0.001). When adjusted for age, gender, smoking, hypertension, alcohol use, physical activity, and LDL-C, we observed an inverse association between HDL-C and its subfractions and CAC (p < 0.05). However, by adding triglycerides in the adjustment, neither total HDL-C nor its subfractions remained independently associated with the presence or extent of CAC. CONCLUSION: In this cross-sectional analysis, neither the total HDL-C nor its subfractions (HDL2-C and HDL3-C, as well as HDL2-C/HDL3-C ratio) measured by VAP are independently associated with the presence or extent of coronary calcification.

6.
Soc Sci Med ; 242: 112591, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31630009

RESUMO

RATIONALE: Familial Hypercholesterolemia (FH) is a genetic condition that predisposes patients to substantially increased risk of early-onset atherosclerotic cardiovascular disease. FH risks can be minimized through regular participation in three self-management. BEHAVIORS: physical activity, healthy eating, and taking cholesterol lowering medication. OBJECTIVE: The present study tested the effectiveness of an integrated social cognition model in predicting intention to participate in the self-management behaviors in FH patients from seven countries. METHOD: Consecutive patients in FH clinics from Australia, Hong Kong, Brazil, Malaysia, Taiwan, China, and UK (total N = 726) completed measures of social cognitive beliefs about illness from the common sense model of self-regulation, beliefs about behaviors from the theory of planned behavior, and past behavior for the three self-management behaviors. RESULTS: Structural equation models indicated that beliefs about behaviors from the theory of planned behavior, namely, attitudes, subjective norms, and perceived behavioral control, were consistent predictors of intention across samples and behaviors. By comparison, effects of beliefs about illness from the common sense model were smaller and trivial in size. Beliefs partially mediated past behavior effects on intention, although indirect effects of past behavior on intention were larger for physical activity relative to taking medication and healthy eating. Model constructs did not fully account for past behavior effects on intentions. Variability in the strength of the beliefs about behaviors was observed across samples and behaviors. CONCLUSION: Current findings outline the importance of beliefs about behaviors as predictors of FH self-management behaviors. Variability in the relative contribution of the beliefs across samples and behaviors highlights the imperative of identifying sample- and behavior-specific correlates of FH self-management behaviors.

7.
Curr Opin Lipidol ; 30(6): 419-427, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31577610

RESUMO

PURPOSE OF REVIEW: Atherogenic dyslipidaemia, characterized by high plasma triglycerides (a surrogate for triglyceride-rich remnant lipoproteins) and low high-density lipoprotein cholesterol (HDL-C), is prevalent in patients with type 2 diabetes mellitus (T2DM) and contributes to a high modifiable residual cardiovascular risk. Fibrates are effective in managing hypertriglyceridaemia but lack consistent cardiovascular benefit in clinical trials and exhibit pharmacokinetic interaction with statins (gemfibrozil) and renal and hepatic safety issues (fenofibrate). The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm offers potential for improving potency, selectivity and the benefit-risk profile. RECENT FINDINGS: The present review discusses evidence for the novel SPPARMα agonist, pemafibrate. Clinical trials showed robust lowering of triglyceride-rich lipoproteins, elevation in HDL-C and nonlipid beneficial effects including anti-inflammatory activity. There was a favourable safety profile, with no increase in serum creatinine, evident with fenofibrate, and improved renal and hepatic safety. The cardiovascular outcomes study PROMINENT is critical to confirming the SPPARMα concept by validating reduction in residual cardiovascular risk in patients with T2DM and long-term safety. SUMMARY: SPPARMα offers a new paradigm for reducing residual cardiovascular risk in T2DM. PROMINENT will be critical to differentiating the first SPPARMα, pemafibrate, as a novel therapeutic class distinct from current fibrates.

8.
Eur J Prev Cardiol ; : 2047487319880985, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31604401

RESUMO

AIMS: Familial hypercholesterolemia patients are characterized by early onset of coronary artery calcification and atherosclerosis, and high incidence of cardiovascular events. Plasma proprotein convertase subtilisin/kexin type 9 was reported to be a predictor for cardiovascular risk in the general population. However, its prognostic value for predicting recurrent cardiovascular events in familial hypercholesterolemia patients remains undetermined. METHODS: A total of 249 patients with molecularly and/or clinically (Dutch Lipid Clinic Network score > 6) defined familial hypercholesterolemia who had experienced a first cardiovascular event were consecutively included and plasma proprotein convertase subtilisin/kexin type 9 concentrations were measured by enzyme-linked immunosorbent assay. Coronary artery calcification was measured using Agatston method and coronary severity was assessed by Gensini score, respectively. All patients received standard lipid-lowering therapy and were followed-up for recurrent cardiovascular events. Univariate and multivariate regression and Cox analyses was used to calculate hazard ratios with 95% confidence interval. RESULTS: Circulating proprotein convertase subtilisin/kexin type 9 concentrations were positively associated with coronary artery calcification scores and Gensini score by both univariate and multivariate analyses. During a mean follow-up of 43 ± 19 months, 29 (11.51%) recurrent cardiovascular events occurred. Kaplan-Meier analysis showed that patients with the highest proprotein convertase subtilisin/kexin type 9 levels had the lowest event-free survival time. Multivariable Cox regression analysis revealed that proprotein convertase subtilisin/kexin type 9 was independently associated with recurrent cardiovascular events (hazard ratio: 1.45, 95% confidence interval: 1.11-1.88). The combination of proprotein convertase subtilisin/kexin type 9 to Cox prediction model led to an enhanced predictive value for recurrent cardiovascular events. CONCLUSIONS: Increased level of proprotein convertase subtilisin/kexin type 9 was a significant risk factor of atherosclerosis and independently predicted future recurrent cardiovascular events in familial hypercholesterolemia patients receiving standard lipid-lowering treatment.

9.
Eur J Prev Cardiol ; : 2047487319876765, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537123
10.
Eur J Prev Cardiol ; : 2047487319871735, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31533447

RESUMO

BACKGROUND: Comprehensive control of multiple cardiovascular risk factors reduces cardiovascular risk but is difficult to achieve. DESIGN: A multinational, cross-sectional, observational study. METHODS: The International ChoLesterol management Practice Study (ICLPS) investigated achievement of European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline low-density lipoprotein cholesterol (LDL-C) targets in patients receiving lipid-modifying therapy in countries outside Western Europe. We examined the rate of, and association between, control of multiple risk factors in ICLPS participants with dyslipidaemia, diabetes and hypertension (N = 2377). RESULTS: Mean (standard deviation) age of patients was 61.4 (10.4) years; 51.3% were male. Type 2 diabetes was the most common form of diabetes (prevalence, 96.9%). The prevalence of metabolic syndrome was 67.8%, obesity 40.4%, atherosclerotic disease 39.6% and coronary artery disease 33.5%. All patients were at high (38.2%) or very high (61.8%) cardiovascular risk according to ESC/EAS guidelines. Body mass index (BMI) was <25 kg/m2 in 20.3% of patients, 62.8% had never smoked and 25.2% were former smokers. Overall, 12.2% achieved simultaneous control of LDL-C, diabetes and blood pressure. Risk factor control was similar across all participating countries. The proportion of patients achieving individual guideline-specified treatment targets was 43.9% for LDL-C, 55.5% for blood pressure and 39.3% for diabetes. Multiple correspondence analysis indicated that control of LDL-C, control of blood pressure, control of diabetes, BMI and smoking were associated. CONCLUSION: Comprehensive control of multiple cardiovascular risk factors in high-risk patients is suboptimal worldwide. Failure to control one risk factor is associated with poor control of other risk factors.

12.
J Clin Lipidol ; 13(5): 735-743, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31377052

RESUMO

BACKGROUND: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease. OBJECTIVE: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status. METHODS: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24-104 weeks' duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non-familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75 mg every 2 weeks (Q2W) to 150 mg Q2W at Week 12 if predefined risk-based LDL-C goals were not achieved at Week 8 (≥70 mg/dL in very high cardiovascular risk; ≥100 mg/dL in moderate or high cardiovascular risk). Two trials compared alirocumab 150 mg Q2W vs placebo. The efficacy and safety of alirocumab were assessed post hoc in subgroups stratified by age (<65, ≥65 to <75, ≥75 years) and baseline hypertension or smoking status. RESULTS: Alirocumab reduced LDL-C by 23.7% (75/150 mg vs ezetimibe + statin) to 65.4% (150 mg vs placebo + statin) from baseline to Week 24 vs control. Subgroup analyses confirmed no significant interactions in response to alirocumab between age group, hypertension, or smoking status. Overall rates of treatment-emergent adverse events were similar between alirocumab and control groups. CONCLUSIONS: In this pooled analysis from 10 trials, alirocumab led to substantial LDL-C reductions vs control in every age group and regardless of hypertension or smoking status. Alirocumab was well tolerated in all subgroups.

13.
J Clin Lipidol ; 13(5): 804-811.e2, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31383603

RESUMO

BACKGROUND: The Martin/Hopkins low-density lipoprotein cholesterol equation (LDL-CN) was previously demonstrated as more accurate than Friedewald LDL-C estimation (LDL-CF) in a North American database not able to take race into account. OBJECTIVES: We hypothesized that LDL-CN would be more accurate than LDL-CF and correlate better with LDL particle number (LDL-P) in a racially diverse Brazilian cohort. METHODS: We performed a cross-sectional analysis of 4897 participants in the Brazilian Longitudinal Study of Adult Health, assessing LDL-CF and LDL-CN accuracy via overlap with ultracentrifugation-based measurement among clinical guideline LDL-C categories as well as mg/dL and percent error differences. We analyzed by triglyceride categories and correlated LDL-C estimation with LDL-P. RESULTS: LDL-CN demonstrated improved accuracy at 70 to <100 and <70 mg/dL (P < .001), with large errors ≥20 mg/dL about 9 times more frequent in LDL-CF at LDL-C <70 mg/dL, mainly due to underestimation. Among individuals with LDL-C <70 mg/dL and triglycerides ≥150 mg/dL, 65% vs 100% of ultracentrifugation-based low-density lipoprotein cholesterol calculation fell within appropriate categories of estimated LDL-CF and LDL-CN, respectively (P < .001). Similar results were observed when analyzed for age, sex, and race. Participants at LDL-C <70 and 70 to <100 mg/dL with discordantly elevated LDL-CN vs LDL-CF had a 58.5% and 41.5% higher LDL-P than those with concordance (P < .0001), respectively. CONCLUSIONS: In a diverse Brazilian cohort, LDL-CN was more accurate than LDL-CF at low LDL-C and high triglycerides. LDL-CN may avoid underestimation of LDL-C and better reflect atherogenic lipid burden in low particle size, high particle count states.

14.
Curr Opin Cardiol ; 34(5): 526-530, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31393421

RESUMO

PURPOSE OF REVIEW: To discuss recent findings related to epidemiology, diagnosis, natural history, atherosclerotic cardiovascular disease (ASCVD) risk heterogeneity and stratification, and treatment of familial hypercholesterolemia. RECENT FINDINGS: Familial hypercholesterolemia persists subdiagnosed, inadequately treated and social disparities aggravate this scenario. Molecular diagnosis is recommended but still not widely available and reimbursed, also recent reclassification of genetic variants associated with familial hypercholesterolemia limits its routine use. New familial hypercholesterolemia clinical diagnostic criteria like FAMCAT are being tested and are apparently more accurate than the classical ones. Genetic traits for familial hypercholesterolemia and high lipoprotein(a) concentrations apparently co-exist and are associated with a higher ASVCD risk than each alone. Indeed, ASCVD risk is heterogenous in heterozygous familial hypercholesterolemia and prospective studies show that it is influenced not only by high LDL-C but also by other risk features like smoking, hypertension, or diabetes. Coronary artery calcification might indicate a higher risk familial hypercholesterolemia population that could benefit from further LDL-C lowering with PCSK9 inhibitors. The latter medications may reduce ASCVD risk in familial hypercholesterolemia individuals similarly to their impact on the general population as shown in a randomized prospective development program (SPIRE). SUMMARY: Knowledge about familial hypercholesterolemia has improved but there are still many challenges for its optimal management.

15.
Curr Opin Lipidol ; 30(5): 414-416, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31460946
16.
Lancet Diabetes Endocrinol ; 7(9): 715-725, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301983

RESUMO

Findings from epidemiological studies over the past 30 years have shown that visceral adipose tissue, accurately measured by CT or MRI, is an independent risk marker of cardiovascular and metabolic morbidity and mortality. Emerging evidence also suggests that ectopic fat deposition, including hepatic and epicardial fat, might contribute to increased atherosclerosis and cardiometabolic risk. This joint position statement from the International Atherosclerosis Society and the International Chair on Cardiometabolic Risk Working Group on Visceral Obesity summarises the evidence for visceral adiposity and ectopic fat as emerging risk factors for type 2 diabetes, atherosclerosis, and cardiovascular disease, with a focus on practical recommendations for health professionals and future directions for research and clinical practice. We discuss the measurement of visceral and ectopic fat, pathophysiology and contribution to adverse health outcomes, response to treatment, and lessons from a public health programme targeting visceral and ectopic fat. We identify knowledge gaps and note the need to develop simple, clinically applicable tools to be able to monitor changes in visceral and ectopic fat over time. Finally, we recognise the need for public health messaging to focus on visceral and ectopic fat in addition to excess bodyweight to better combat the growing epidemic of obesity worldwide.

17.
Cardiovasc Diabetol ; 18(1): 71, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164165

RESUMO

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

18.
J Clin Lipidol ; 13(4): 594-600, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31208705

RESUMO

BACKGROUND: The cross-sectional observational International ChoLesterol management Practice Study study assessed achievement of European Society of Cardiology/European Atherosclerosis Society low-density lipoprotein cholesterol (LDL-C) targets in patients outside Western Europe. OBJECTIVE: The aim of the study was to assess LDL-C goal achievement in International ChoLesterol management Practice Study participants with familial hypercholesterolemia (FH). METHODS: A total of 334 patients (aged ≥18 years) with definite or probable FH (Dutch Lipid Clinic Network score ≥6; 43.1% genetically confirmed) who had been receiving stable lipid-modifying therapy (LMT) for ≥3 months were enrolled. RESULTS: The mean ± standard deviation age of the patients was 58.5 ± 13.1 years, 49.1% were male, and 48.2% had coronary artery disease. Most were receiving statin (∼99%). Of these, 57.6% were on high-intensity statin therapy, 49.1% on the highest dose available, and 13.0% used a statin together with a cholesterol absorption inhibitor (CAI). Mean ± standard deviation LDL-C level was 5.6 ± 3.0 mmol/L before LMT and 3.3 ± 2.0 mmol/L at enrollment. Overall, 32.0% of patients achieved their LDL-C target. Target achievement rates were 36.6% for patients with coronary artery disease, and 27.5% for those without, and 27.9%, 28.0%, and 37.5% for patients treated with a statin plus CAI, highest-dose statin (no CAI), and lower-dose statin (no CAI), respectively. CONCLUSIONS: LDL-C target achievement rates were low in patients with FH, even in those receiving intensive LMT. Factors that are likely to have contributed to the low LDL-C target achievement rates include high baseline LDL-C, inadequate statin dosages, and low use of CAI. Many patients would have been eligible for proprotein convertase subtilisin/kexin type 9 inhibitor therapy.

19.
Atherosclerosis ; 286: 40-45, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31100618

RESUMO

BACKGROUND AND AIMS: Patients with familial hypercholesterolaemia (FH) may require proprotein convertase subtilisin/kexin-type 9 (PCSK9) mAb as add-on therapy to achieve LDL-cholesterol (LDL-C) goals. However, the current cost of these therapies means that choosing suitable patients is based on consensus or clinical judgement rather than a quantitative risk assessment. We used the SAFEHEART Risk Equation (RE) to estimate the number needed to treat (NNT) at different risk thresholds and baseline LDL-C to identify those FH patients more likely to derive the greatest benefit from PCSK9 mAb. METHODS: Five-year event rates were calculated using the SAFEHEART-RE for every patient, overall and across LDL-C strata. A 60% reduction of LDL-C after theoretical treatment with PCSK9 mAb was assumed. Individual absolute risk simulating the effects of PCSK9 inhibition was calculated using the SAFEHEART-RE and, in a similar way, by using the Cholesterol Treatment Trialists' (CTT) Collaboration criteria. Absolute risk reduction and NNTs were calculated. RESULTS: Of the total SAFEHEART population, 2,153 were FH cases aged 18 years or older, on maximum tolerated lipid lowering treatment. NNTs were dependent of both baseline predicted risk and baseline LDL-C level ranging from 44 to 17 for those with 5-year risk of ≥1 to ≥5. The smallest NNT (12) was observed among those with 5-year risk of ≥5% and LDL-C ≥160 mg/dl. Using the CTT criteria produced similar results. CONCLUSIONS: The SAFEHEART-RE may provide a useful quantitative tool for rationalising the selection of FH patients who might derive greater absolute benefits from PCSK9 mAb.

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