Background: Although risk factors for atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolemia (FH) have been described, models for predicting incident ASCVD have not been reported. Our aim was to use the SAFEHEART registry (Spanish Familial Hypercholesterolemia Cohort Study) to define key risk factors for predicting incident ASCVD in patients with FH. Methods: SAFEHEART is a multicenter, nationwide, long-term prospective cohort study of a molecularly defined population with FH with or without previous ASCVD. Analyses to define risk factors and to build a risk prediction equation were developed, and the risk prediction equation was tested for its ability to discriminate patients who experience incident ASCVD from those who did not over time. Results: We recruited 2404 adult patients with FH who were followed up for a mean of 5.5 years (SD, 3.2 years), during which 12 (0.5%) and 122 (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 lipoprotein(a) levels were independent predictors of incident ASCVD from which a risk equation with a Harrell C index of 0.85 was derived. The bootstrap resampling (100 randomized samples) of the original set for internal validation showed a degree of overoptimism of 0.003. Individual risk was estimated for each person without an established diagnosis of ASCVD before enrollment in the registry by use of the SAFEHEART risk equation, the modified Framingham risk equation, and the American College of Cardiology/American Heart Association ASCVD Pooled Cohort Risk Equations. The Harrell C index for these models was 0.81, 0.78, and 0.8, respectively, and differences between the SAFEHEART risk equation and the other 2 were significant ( P =0.023 and P =0.045). Conclusions: The risk of incident ASCVD may be estimated in patients with FH with simple clinical predictors. This finding may improve risk stratification and could be used to guide therapy in patients with FH. Clinical Trial Registration: URL: http://clinicaltrials.gov . Unique identifier: NCT02693548.

Introduction: The body roundness index (BRI) and a body shape index (ABSI) are novel anthropometric indices established to determine both the amount visceral adipose tissue and body fat. Objective: to investigate whether BRI and ABSI are better predictors of hypertension than body mass index (BMI), waist circumference (WC) or waist-to-height ratio (WHtR). Methods: A systematic search was conducted in the Scopus, PubMed and Web of Science databases up until 31 December 2020. Results: The estimated pooled area under curve [AUC (95% CI)] for BRI [0.67 (0.65–0.70)] for the prediction of hypertension were superior to that of ABSI (0.58 (0.56–0.60)), similar to that of BMI [0.67 (0.64–0.69)], and lower than those WC [0.68 (0.66–0.70)] and WHtR [0.68 (0.66–0.71)]. Nevertheless, the difference of BRI compared to WC and WHtR in the context of predicting hypertension was non-significant. ABSI was significantly lower (p < 0.05) than BRI, BMI, WC and WHtR. Similar findings were observed with the summary receiver operating characteristic curve (AUC-SROC). There were no significant differences between subgroups according to type of population or diagnostic criteria of hypertension. The diagnostic odds ratio (dORs) proved that increased BRI and ABSI were related with an elevated hypertension risk. Conclusions: BRI and ABSI have discriminatory power for hypertension in adult women and men from different populations. Although, WHtR and WC provided the best performance when assessing hypertension, no significant differences were found for BRI. Finally, BRI was significantly better predictor of hypertension than ABSI.

Familial hypercholesterolemia (FH) patients are at high risk for premature coronary heart disease (CHD). Despite the use of statins, most patients do not achieve an optimal LDL-cholesterol goal. The aims of this study are to describe baseline characteristics and to evaluate Lipid Lowering Therapy (LLT) in FH patients recruited in SAFEHEART. A cross-sectional analysis of cases recruited in the Spanish FH cohort at inclusion was performed. Demographic, lifestyle, medical and therapeutic data were collected by specific surveys. Blood samples for lipid profile and DNA were obtained. Genetic test for FH was performed through DNA-microarray. Data from 1852 subjects (47.5% males) over 19 years old were analyzed: 1262 (68.1%, mean age 45.6 years) had genetic diagnosis of FH and 590 (31.9%, mean age 41.3 years) were non-FH. Cardiovascular disease was present in 14% of FH and in 3.2% of non-FH subjects (P < 0.001), and was significantly higher in patients carrying a null mutation compared with those carrying a defective mutation (14.87% vs. 10.6%, respectively, P < 0.05). Prevalence of current smokers was 28.4% in FH subjects. Most FH cases were receiving LLT (84%). Although 51.5% were receiving treatment expected to reduce LDL-c levels at least 50%, only 13.6% were on maximum statin dose combined with ezetimibe. Mean LDL-c level in treated FH cases was 186.5 mg/dl (SD: 65.6) and only 3.4% of patients reached and LDL-c under 100 mg/dl. The best predictor for LDL-c goal attainment was the use of combined therapy with statin and ezetimibe. Although most of this high risk population is receiving LLT, prevalence of cardiovascular disease and LDL-c levels are still high and far from the optimum LDL-c therapeutic goal. However, LDL-c levels could be reduced by using more intensive LLT such as combined therapy with maximum statin dose and ezetimibe.

Background: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. Methods: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. Results: The study was completed by 104 patients. The median age was 53.3 (46.2–59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5–175.3) mg/dL at entry and 45.0 (36.0–65.0) mg/dL at follow-up ( P <0.001). Coronary plaque burden changed from 34.6% (32.5%–36.8%) at entry to 30.4% (27.4%–33.4%) at follow-up ( P <0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P <0.001) and mainly fibrous (+6.2%; P <0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (–3.9%; P <0.001) and necrotic plaque (–0.6%; P <0.001). Conclusions: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05465278.