PAULO CALEB JUNIOR DE LIMA SANTOS
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
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- Impact of diabetes mellitus on arterial stiffness in a representative sample of an urban Brazilian population(2013) ALVIM, Rafael de Oliveira; SANTOS, Paulo Caleb Junior Lima; MUSSO, Mariane Manso; CUNHA, Roberto de Sa; KRIEGER, Jose Eduardo; MILL, Jose Geraldo; PEREIRA, Alexandre CostaBackground: Independent of other cardiovascular (CV) risk factors, increased arterial stiffness has been established as a predictor of morbidity and mortality. The main aim of this study was to investigate the impact of diabetes on arterial stiffness in a representative sample of an urban Brazilian population plus Amerindians. Methods: A total of 1,415 individuals from the general population were randomly selected plus 588 Amerindians from a native community in Brazil. In addition, a sub-sample of 380 individuals from the general population had 5-year follow-up data. Pulse wave velocity (PWV) was measured with a non-invasive automatic device (Complior, Colson; Garges les Gonesses, France) and increased arterial stiffness was defined as PWV >= 12 m/s. Results: In the overall group, diabetic individuals had higher frequencies of increased arterial stiffness and hypertension. They also had higher values of PWV, body mass index, total cholesterol, triglycerides, systolic and diastolic blood pressures compared to non-diabetic individuals (p < 0.01). In an analysis stratified by hypertension, PWV values and increased arterial stiffness frequency were higher in diabetic individuals in both groups (hypertensive and non-hypertensive) (p < 0.05). Furthermore, higher risk for increased arterial stiffness was observed in the diabetic individuals from the overall group (OR = 2.27; CI = 1.47-3.52, p < 0.001) and from the hypertensive group (OR = 2.70; CI = 1.58-4.75, p < 0.001), adjusted for covariates. Regarding the ethnic stratification, diabetic individuals from Amerindian, White, and Mulatto (mixed-race) groups had higher PWV values and a greater frequency of increased arterial stiffness compared to non-diabetic individuals. Both diabetic and non-diabetic individuals had higher PWV values after 5 years. There was no significant difference in the 5-year PWV progression in diabetic compared to non-diabetic individuals. Conclusions: These results confirm, in a sample of Brazilian population, that the presence of diabetes is associated with increased arterial stiffness and it may contribute in part to increased cardiovascular risk in diabetic patients.
- CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability in patients on long-term anticoagulation(2013) SANTOS, Paulo Caleb Junior Lima; DINARDO, Carla Luana; SCHETTERT, Isolmar Tadeu; SOARES, Renata Alonso Gadi; KAWABATA-YOSHIHARA, Liz; BENSENOR, Isabela Martins; KRIEGER, Jose Eduardo; LOTUFO, Paulo Andrade; PEREIRA, Alexandre CostaThe main aim of this study was to determine whether CYP2C9 and VKORC1 polymorphisms influence warfarin dose variability during initial dose-finding phase and during maintenance treatment after 360 days. Two hundred and six consecutive patients who were beginning warfarin therapy were selected. They were assessed for general and clinical characteristics; prescribed warfarin dose; response to therapy on days 7-10, 30, 60, 180, and 360; adverse events; and CYP2C9 *2, *3, *5, *6, *8, *11, and VKORC1 1639G > A assays. During the first 30 days of anticoagulation, the relative variability of warfarin dose was significantly associated with CYP2C9*2 and CYP2C9*3 polymorphisms (p = 0.02) and with VKORC1 1639G > A genotypes (p = 0.04). Warfarin variability was also statistically different according to predicted metabolic phenotype and to VKORC1 genotypes after 360 days of treatment, and in the phase between 180 and 360 days (long-term dose variability). Both CYP2C9 and VKORC1 polymorphisms were associated with the international normalized ratio (INR) made between 7 and 10 days/initial dose ratio, adjusted for covariates (p < 0.01 and p = 0.02, respectively). Patients carrying VKORC1 and CYP2C9 variants presented lower required dose (at the end of follow-up of 360 days) compared to patients carrying wild-type genotypes (p = 0.04 and p = 0.03, respectively). Genetic information on CYP2C9 and VKORC1 is important both for the initial dose-finding phase and during maintenance treatment with warfarin.
- Effectiveness of Coadministration of Varenicline, Bupropion, and Serotonin Reuptake Inhibitors in a Smoking Cessation Program in the Real-Life Setting(2013) ISSA, Jaqueline S.; ABE, Tania Ogawa; MOURA, Simone; SANTOS, Paulo C. J. L.; PEREIRA, Alexandre C.Introduction: Varenicline has a significant impact on the ability to quit smoking. However, patients may have side effects similar to nicotine withdrawal symptoms. The aim of this study was to evaluate the effectiveness of varenicline in monotherapy or in combined therapy with bupropion and/or serotonin reuptake inhibitors (SRIs) in a specific cardiovascular smoking cessation service. Methods: It is an outcome research of 427 patients that received varenicline monotherapy or combined pharmacotherapy and were followed for 52 weeks. Patients were oriented to take varenicline until week 12. During each medical visit, the patients were evaluated and in the cases of mood changes after varenicline use, SRIs were prescribed. Bupropion was combined in patients that did not achieve complete tobacco abstinence in 2 or 3 weeks after starting varenicline use or if the patient presented uncomfortable abstinent symptoms. Results: The success (continuous abstinence rate in 52 weeks) in different drug regimens were: varenicline monotherapy (32.1%), varenicline + bupropion (55.0%), varenicline + SRI (50.6%), and varenicline + bupropion + SRI (57.7%). In a multivariate analysis of successful treatment predictors, compared with varenicline monotherapy, patients who used bupropion + SRI adjuvant treatment had an odds ratio (OR) of 5.05 (1.99-12.80) for a successful treatment response after 1-year follow-up, while patients who used bupropion or SRI had OR of 3.21 (1.68-6.14) and 3.58 (1.98-6.48), respectively. Conclusions: Our results suggest that adjuvant treatment to varenicline therapy may be associated with improved success in smoking cessation, especially in patients with nicotine withdrawal symptoms. These results should be tested in randomized controlled trials.
- Association between UCP2 A55V polymorphism and risk of cardiovascular events in patients with multi-vessel coronary arterial disease(2013) GIOLI-PEREIRA, Luciana; SANTOS, Paulo C. J. L.; SUGAYA, Luisa S.; FERREIRA, Noely E.; KRIEGER, Jose Eduardo; PEREIRA, Alexandre C.; HUEB, Whady A.Background: UCP2 (uncoupling protein 2) plays an important role in cardiovascular diseases and recent studies have suggested that the A55V polymorphism can cause UCP2 dysfunction. The main aim was to investigate the association of A55V polymorphism with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease and preserved left ventricular function. Methods: The participants of the MASS II were genotyped for the A55V polymorphism using allele-specific PCR assay. Survival curves were calculated with the Kaplan-Meier method and evaluated with the log-rank statistic. The relationship between baseline variables and the composite end-point of cardiac death, acute myocardial infarction (AMI), refractory angina requiring revascularization and cerebrovascular accident were assessed using a Cox proportional hazards survival model. Results: There were no significant differences for baseline variables according genotypes. After 2 years of follow-up, dysglycemic patients harboring the W genotype had higher occurrence of AMI (p=0.026), Death+AMI (p=0.033), new revascularization intervention (p=0.009) and combined events (p=0.037) as compared with patients carrying other genotypes. This association was not evident in normoglycemic patients. Conclusions: These findings support the hypothesis that A55V polymorphism is associated with UCP2 functional alterations that increase the risk of cardiovascular events in patients with previous coronary artery disease and dysglycemia.