WILSON SALGADO FILHO
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- Achilles tendon xanthomas are associated with the presence and burden of subclinical coronary atherosclerosis in heterozygous familial hypercholesterolemia: A pilot study(2017) MANGILI, Leonardo C.; MINAME, Marcio H.; SILVA, Pamela R. S.; BITTENCOURT, Marcio S.; ROCHA, Viviane Z.; MANGILI, Otavio C.; SALGADO FILHO, Wilson; CHACRA, Ana P.; JANNES, Cinthia E.; PEREIRA, Alexandre C.; SANTOS, Raul D.Background and aims: Achilles tendon xanthomas (ATX) are a sign of long-term exposure to high blood cholesterol in familial hypercholesterolemia (FH) patients, which have been associated with cardiovascular disease. We evaluated the ATX association with the presence and extent of subclinical coronary atherosclerosis in heterozygous FH patients. Methods: 102 FH patients diagnosed by US-MEDPED criteria (67% with genetically proven FH), with median LDL-C 279 mg/dL (interquartile range: 240; 313), asymptomatic for cardiovascular disease, underwent computed tomography angiography and coronary artery calcium (CAC) quantification. Subclinical coronary atherosclerosis was quantified by CAC, segment-stenosis (SSS) and segment-involvement (SIS) scores. Adjusted Poisson regression was used to assess the association of ATX with subclinical atherosclerosis burden as continuous variables. Results: Patients with ATX (n = 21, 21%) had higher LDL-C and lipoprotein(a) [Lp(a)] concentrations as well as greater CAC scores, SIS and SSS (p < 0.05). After adjusting for age, sex, smoking, hypertension, previous statin use, HDL-C, LDL-C and Lp(a) concentrations, there was an independent positive association of ATX presence with CAC scores (beta = 1.017, p < 0.001), SSS (beta = 0.809, p < 0.001) and SIS (beta = 0.640, p < 0.001). Conclusions: ATX are independently associated with the extension of subclinical coronary atherosclerosis quantified by tomographic scores in FH patients.
- Association between postprandial triglycerides and coronary artery disease detected by coronary computed tomography angiography(2014) STANIAK, Henrique L.; FILHO, Wilson Salgado; MINAME, Marcio H.; BENSENOR, Isabela M.; LOTUFO, Paulo A.; SHAROVSKY, Rodolfo; ROCHITTE, Carlos E.; BITTENCOURT, Marcio S.; SANTOS, Raul D.Background: Studies have demonstrated the association of severe anatomical coronary artery disease (CAD) with postprandial triglycerides (TG) concentrations. Nevertheless the relationship between less severe atherosclerosis plaque burden and postprandial TG is less established. Objective: to study the relationship between postprandial TG and CAD detected by coronary computed tomographic angiography (CTA). Material and methods: 130 patients who underwent an oral fat tolerance test were enrolled (85 with CAD detected by CTA and 45 without). Postprandial lipemia was studied by measuring TG from T0h to T6h with 2-h intervals, and analyzed the TG change over time using a longitudinal multivariable linear mixed effects model with the log normal of the TG as the primary outcome. Results: The majority of individuals with CAD had non-obstructive disease (63.3%) Patients with CAD had a slower clearance of postprandial TG change from 4 h to 6 h (p < 0.05) compared to patients without CAD. These results remained significant after adjustment for fasting TG and glucose, age, gender, body mass index, and waist circumference. However, those differences did not reach statistical significance after adjustment for fasting HDL-C. Conclusion: Patients with mild (<25% lumen obstruction) and moderate CAD (25-50% lumen obstruction) detected by coronary CTA had an impaired postprandial metabolism, with a delayed TG clearance, when compared to individuals with no CAD. This difference was partially explained by the lower HDL-C. Thus, though postprandial TG may contribute to the development of CAD, this association is partially related to low HDL-C.
- Familial hypercholesterolemia and cardiovascular disease in older individuals(2021) COUTINHO, Elaine R.; MINAME, Marcio H.; ROCHA, Viviane Z.; BITTENCOURT, Marcio S.; JANNES, Cinthia E.; TADA, Mauricio T.; LIMA, Isabella R.; SALGADO FILHO, Wilson; CHACRA, Ana P.; PEREIRA, Alexandre C.; KRIEGER, Jose E.; SANTOS, Raul D.Background and aims: Familial hypercholestemlemia (FH) is characterized by high LDL-cholesterol (LDL-C) and early atherosclerotic cardiovascular disease (ASCVD). With a lipid lowering therapy (LLT), most individuals with FH may have a longer ASCVD-free survival. However, there is scant data about older individuals with FH. Methods: We compared characteristics of genetically defined FH older individuals with age-matched non-FH counterparts. Results: From 4111 genotyped individuals, 462 older than 60 years were included (198 positive and 264 negative for FH variants). There were no differences regarding median age [%25; 75%] 66.0 (62.0; 71.0) and 66.0 (62.2; 71.0) years, p = 0.68 for FH and non-FH, respectively. In both groups, there was a higher frequency of females, however, there were more males in the FH group 37.4% vs. 24.2%, p = 0.002. No differences were seen between FH and non-FH in LLT use: 88.5% vs. 91.5%, p = 0.29. Despite a longer LLT duration in FH patients (with 11.0 (7.0; 20.0) vs. 7.0 (3.0; 13.0) years, p < 0.001), treatment was started late in both groups: at 54.0 (47.0; 61.0) and 59.0 (52.0; 64.0) years, p < 0.001, in FH and non-FH, respectively. FH had greater frequencies of previous and early ASCVD (40.9% vs. 27.3%, p = 0.002, and 22.2% vs. 9.0%, p < 0.001). In FH, male sex [HR (95%C01 2.67 (1.50-4.73), p = 0.001, and LLT onset age 0.96 (0.93-0.99), p = 0.009, were independently associated with ASCVD. Conclusions: Among hypercholesterolemic older individuals participating in a cascade screening program, the genetic diagnosis of FH was associated with higher ASCVD rates, emphasizing the relevance of a monogenic defect as the cause of long-lasting hypercholesterolemia and ASCVD risk, particularly in men.
- Familial hypercholesterolemia in Brazil: Cascade screening program, clinical and genetic aspects(2015) JANNES, Cinthia E.; SANTOS, Raul D.; SILVA, Pamela R. de Souza; TUROLLA, Luciana; GAGLIARDI, Ana C. M.; MARSIGLIA, Julia D. C.; CHACRA, Ana P.; MINAME, Marcio H.; ROCHA, Viviane Z.; SALGADO FILHO, Wilson; KRIEGER, Jose E.; PEREIRA, Alexandre C.Background: There is little knowledge about familial hypercholesterolemia in Brazil. This study presents the first results of genetic cascade screening performed in the city of Sao Paulo. Material and methods: Two-hundred and forty-eight suspected index cases were initially included. DNA was extracted from peripheral blood and the complete coding sequence of low-density lipoprotein receptor, exon 7 of proprotein convertase subtilisin/kexin type 9 gene and part of exon 26 of apolipoprotein B genes were sequenced. Multiplex Ligation-dependent Probe Amplification was performed on cases where a causal mutation was not identified through sequencing. After the identification of a causal mutation screening in first-degree relatives was pursued. Results: From 248 index cases, a mutation was found in 125 individuals (50.4%). 394 relatives were included in the cascade screening program and a mutation was identified in 59.4%. Seventy different causal mutations in the low-density lipoprotein receptor gene (97.2%) and 2 in the apolipoprotein B gene (2.8%) were found. No mutations were encountered in the proprotein convertase subtilisin/ kexin type 9 gene. Mutations in exons 14 and 4 were the most prevalent and, 10 cases of true homozygotes (8 index cases and 2 relatives) and 1 compound heterozygote were identified. The most frequent mutation found was of Lebanese origin, the p.(Cys681*) mutation in exon 14 (8.5%). Conclusion: Genetic familial hypercholesterolemia cascade screening is feasible in Brazil and leads to identification of a mutation in approximately half of the index cases with higher rates of success in their relatives.