GIULIANO GENEROSO
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- Predictors of coronary artery calcium incidence and progression: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)(2020) CARDOSO, Rhanderson; GENEROSO, Giuliano; STANIAK, Henrique L.; FOPPA, Murilo; DUNCAN, Bruce B.; PEREIRA, Alexandre C.; BLAHA, Michael J.; BLANKSTEIN, Ron; NASIR, Khurram; BENSENOR, Isabela M.; LOTUFO, Paulo A.; BITTENCOURT, Marcio S.Background and aims: There are limited data on serial coronary artery calcium (CAC) assessments outside North American and European populations. We sought to investigate risk factors for CAC incidence and progression in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: We included individuals with no prior cardiovascular disease and two CAC measurements in ELSA-Brasil. Incident CAC was defined as a baseline CAC of 0 followed by CAC > 0 on the second study. CAC progression was defined according to multiple published criteria. We performed logistic and linear regression to identify risk factors for CAC incidence and progression. We also examined risk factor effect modification by baseline CAC (0 vs. > 0). Results: A total of 2707 individuals were included (57% women, age 48.6 +/- 7.7 years). Participants self-identified as white (55%), brown (24%), black (16%), Asian (4%) and Indigenous (1%). The mean period between CAC assessments was 5.1 +/- 0.9 years. CAC incidence occurred in 282 (13.3%) of 2127 individuals with baseline CAC of 0. CAC progression occurred in 319 (55%) of 580 participants with baseline CAC > 0. Risk factors for CAC incidence included older age, male sex, white race, hypertension, diabetes, higher BMI, smoking, lower HDL-C, higher LDL-C and triglycerides, and metabolic syndrome. Older age and elevated LDL-C were associated with CAC incidence, but not progression. Risk factors consistently associated with CAC progression were hypertension, diabetes, hypertriglyceridemia, and metabolic syndrome. On interaction testing, these four risk factors were more strongly associated with CAC progression as compared to CAC incidence. Conclusions: CAC incidence was associated with multiple traditional risk factors, whereas the only risk factors associated with progression of CAC were hypertension, diabetes, hypertriglyceridemia, and metabolic syndrome.
conferenceObject Association Between HDL-P Subfractions and Intima-Media Carotid Thickness.(2018) GENEROSO, Giuliano; BENSENOR, Isabela M.; SANTOS, Raul D.; SANTOS, Itamar S.; JONES, Steven R.; OTVOS, James D.; BLAHA, Michael J.; TOTH, Peter P.; LOTUFO, Paulo A.; BITTENCOURT, Marcio S.- The association between triglyceride-rich lipoproteins, circulating leukocytes, and low-grade inflammation: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)(2023) CESENA, Fernando Yue; GENEROSO, Giuliano; SANTOS, Raul D.; PEREIRA, Alexandre Costa; BLAHA, Michael J.; JONES, Steven R.; TOTH, Peter P.; LOTUFO, Paulo A.; BITTENCOURT, Marcio Sommer; BENSENOR, Isabela M.Background: Experimental studies have linked triglyceride-rich lipoproteins (TRLs) to inflamma-tion, but the extent of this phenomenon in vivo has not been completely elucidated.Objective: We investigated the association between TRL subparticles and inflammatory markers (circulating leukocytes, plasma high-sensitivity C-reactive protein [hs-CRP], and GlycA) in the general population.Methods: This was a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). TRLs (number of particles per unit volume) and GlycA were measured by nuclear mag-netic resonance spectroscopy. The association between TRLs and inflammatory mark ers w as determined by multiple linear regression models adjusted for demographic data, metabolic conditions, and lifestyle factors. Standardized regression coefficients (beta) with 95% confidence intervals are reported. Results: The study population comprised 4,001 individuals (54% females, age 50 +/- 9 years). TRLs, especially medium and large subparticles, were associated with GlycA (beta 0.202 [0.168, 0.235], p < 0.001 for total TRLs). There was no association between TRLs and hs-CRP (beta 0.022 [-0.011, 0.056], p = 0.190). Medium, large, and very large TRLs were associated with leukocytes, with stronger connections with neutrophils and lymphocytes than monocytes. When TRL subclasses were analyzed as the proportion of the total pool of TRL particles, medium and large TRLs were positively related to leukocytes and GlycA, whereas smaller particles were inversely associated.Conclusions: There are different patterns of association between TRL subparticles and inflammatory markers. The findings support the hypothesis that TRLs (especially medium and larger subparticles) may induce a low-grade inflammatory environment that involves leukocyte activation and is captured by GlycA, but not hs-CRP.(c) 2023 National Lipid Association.
- Dietary patterns and subclinical atherosclerosis incidence and progression: Results from ELSA-Brasil(2023) ALVES, Mariane de A.; MIRANDA, Andreia M.; CACAU, Leandro T.; LEVY, Jessica; GENEROSO, Giuliano; BITTENCOURT, Marcio S.; LOTUFO, Paulo A.; BENSENOR, Isabela M.; MARCHIONI, Dirce M.Background and aims: Cardiovascular disease (CVD) is the main cause of disease burden worldwide. Coronary artery calcification (CAC) score is a subclinical atherosclerosis marker able to predict the risk of CVD in asymptomatic patients, and few studies have investigated the association between dietary patterns (DP) and CAC score prospectively. Thus, the aim of this study was to estimate the association between baseline DP and CAC score incidence and progression on the ELSA-Brasil cohort. Methods and results: This study is a longitudinal prospective analysis of the ELSA-Brasil participants who underwent a CAC exam on baseline and follow-up (n = 2,824). CAC incidence was defined as a baseline CAC score equal to zero (n = 2,131) and subsequent follow-up CAC score greater than zero. CAC progression was defined according to the Hokanson method for the individuals who presented a CAC score greater than zero at the baseline (n = 639). Dietary data were assessed at the baseline using a food frequency questionnaire (FFQ), and factor analysis was applied to identify DP. Poisson regression models with robust variance and linear regression models were applied to estimate the association between baseline DP and CAC incidence and progression. The incidence of CAC was 14.6%, while 60.3% of the individuals presented CAC progression. Three DP were identified: convenience, Brazilian traditional, and prudent. We did not find a significant association between baseline DP and CAC incidence or progression. Conclusion: Our findings from this longitudinal prospective analysis showed that baseline DP are not associated with CAC incidence or progression. & COPY; 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University.
- High-density Lipoprotein-cholesterol Subfractions and Coronary Artery Calcium: The ELSA-Brasil Study(2019) GENEROSO, Giuliano; BENSENOR, Isabela M.; SANTOS, Raul D.; STANIAK, Henrique L.; SHAROVSKY, Rodolfo; SANTOS, Itamar S.; GOULART, Alessandra C.; JONES, Steven R.; KULKARNI, Krishnan R.; BLAHA, Michael J.; TOTH, Peter P.; LOTUFO, Paulo A.; BITTENCOURT, Marcio S.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/I) 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/I, 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. (C) 2019 IMSS.
- Diabetes alters the association between high-density lipoprotein subfractions and carotid intima-media thickness: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)(2018) GENEROSO, Giuliano; BENSENOR, Isabela M.; SANTOS, Itamar S.; SANTOS, Raul D.; GOULART, Alessandra C.; JONES, Steven R.; KULKARNI, Krishnaji R.; BLAHA, Michael J.; TOTH, Peter P.; LOTUFO, Paulo A.; BITTENCOURT, Marcio SommerIntroduction: High-density lipoprotein cholesterol comprises a group of heterogeneous subfractions that might have differential effects on atherosclerosis. Moreover, prior investigations suggest that the presence of diabetes (T2D) modifies the impact of some subfractions on atherosclerosis. In this study, we aimed to evaluate the association between high-density lipoprotein cholesterol subfractions and carotid intima-media thickness in the baseline assessment of the Brazilian Longitudinal Study of Adult Health participants from the Sao Paulo investigation centre. Methods: We evaluated 3930 individuals between 35 and 74 years without previous cardiovascular disease not using lipid-lowering drugs. High-density lipoprotein cholesterol subfractions (HDL2-C and HDL3-C) were measured by vertical ultracentrifugation (vertical auto profile). The relationship between each high-density lipoprotein cholesterol subfraction and carotid intima-media thickness was analysed by multiple linear regression models. Results: Total high-density lipoprotein cholesterol, as well as HDL2-C and HDL3-C, was negatively associated with carotid intima-media thickness after adjustment for demographic data (all p < 0.001) and traditional risk factors (all p < 0.05). When stratified by T2D status, the HDL2-C/HDL3-C ratio showed a negative association with carotid intima-media thickness in participants with T2D (p = 0.032), even after fully controlling for confounding variables, including total high-density lipoprotein cholesterol. Conclusion: HDL2-C, HDL3-C and HDL2/HDL3-C ratio are inversely associated with carotid intima-media thickness after adjustment for traditional risk factors. Association of the HDL2-C/HDL3-C ratio is modified by the presence of diabetes, being more pronounced in diabetic individuals.
- Combined Association of Novel and Traditional Inflammatory Biomarkers With Carotid Artery Plaque: GlycA Versus C-Reactive Protein (ELSA-Brasil)(2023) TEBAR, William R.; MENEGHINI, Vandrize; GOULART, Alessandra C.; SANTOS, Itamar S.; SANTOS, Raul D.; BITTENCOURT, Marcio S.; GENEROSO, Giuliano; PEREIRA, Alexandre C.; BLAHA, Michael J.; JONES, Steven R.; TOTH, Peter P.; OTVOS, James; LOTUFO, Paulo A.; BENSENOR, Isabela M.Elevated levels of glycoprotein acetylation (GlycA) and C-reactive protein (CRP) have been associated with carotid artery plaque (CAP). However, it is not yet established if elevations in both inflammatory biomarkers provide incremental association with CAP. This study aimed evaluate the cross-sectional association of high CRP and GlycA with CAP at baseline participants from the ELSA-Brasil adult cohort. Participants with information on CRP, GlycA, and CAP with neither previous cardiovascular disease nor CRP >10 mg/ L were included. High GlycA and CRP were defined as values within upper quintile and >3 mg/L, respectively. Participants were classified into 4 groups: 1. nonelevated CRP/ GlycA (reference group); 2. elevated CRP alone; 3. elevated GlycA alone; and 4. both elevated. The analysis included 4,126 participants with median age of 50 years-old, being 54.2% of women. Prevalence of CAP was 36.1%. Participants with high CRP had the highest frequency of obesity, whereas participants with high GlycA presented higher cardiovascular risk factor burden and were more likely to have CAP than the reference group (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.11 to 1.73), persisting after multivariable adjustment (OR 1.37, 95% CI 1.02 to 1.83). Participants with both elevated CRP and GlycA were more likely to have CAP in crude (OR 1.35, 95% CI 1.10 to 1.65) but not in adjusted models. The findings suggest potential different biologic pathways between inflammation and carotid atherosclerosis: high GlycA was associated with CAP whereas high CRP was more associated with obesity. & COPY; 2023 Elsevier Inc. All rights reserved. (Am J Cardiol 2023;204:140-150)
- Percentiles of predicted 10-year cardiovascular disease risk by sex and age in Brazil and their association with estimated risk of long-term atherosclerotic events(2023) CESENA, Fernando Yue; GENEROSO, Giuliano; SANTOS, Itamar de S.; DUNCAN, Bruce B.; RIBEIRO, Antonio Luiz P.; BRANT, Luisa Caldeira; MILL, Jose Geraldo; PEREIRA, Alexandre C.; BITTENCOURT, Marcio Sommer; SANTOS, Raul D.; LOTUFO, Paulo A.; BENSENOR, Isabela M.Objective: Expressing the cardiovascular disease (CVD) risk in relation to peers may complement the estimation of absolute CVD risk. We aimed to determine 10-year CVD risk percentiles by sex and age in the Brazilian population and evaluate their association with estimated long-term atherosclerotic CVD (ASCVD) risk.Methods: A cross-sectional analysis of baseline data from the ELSA-Brasil study was conducted in individuals aged 40-74 years without prior ASCVD. Ten-year CVD risk and long-term ASCVD risk were estimated by the WHO risk score and the Multinational Cardiovascular Risk Consortium tool, respectively. Ten-year risk percentiles were determined by ranking the calculated risks within each sex and age group.Results: Ten-year CVD risk versus percentile plots were constructed for each sex and age group using data from 13,364 participants (55% females; median age, 52 [IQR, 46-59] years). Long-term ASCVD risk was calculated in 12,973 (97.1%) participants. Compared to individuals at the <25th risk percentile, those at the >= 75th percentile had a greater risk of being in the highest quartile of long-term risk (ORs [95% CIs] 6.57 [5.18-8.30] in females and 11.59 [8.42-15.96] in males) in regression models adjusted for age, race, education, and 10-year CVD risk. In both sexes, the association between risk percentile and long-term risk weakened after age 50. A tool for calculating 10-year CVD risk and the corresponding percentile is available at https://bit.ly/3CzPUi6.Conclusions: We established percentiles of predicted 10-year CVD risk by sex and age in the Brazilian population, which independently reflect the estimated long-term ASCVD risk in younger individuals.
conferenceObject Hdl Mean Size is Associated With Coronary Artery Calcification, While Hdl-p and Its Subfractions Are Not(2019) GENEROSO, Giuliano; BENSENOR, Isabela M.; SANTOS, Raul; SANTOS, Itamar S.; JONES, Steven R.; BLAHA, Michael J.; TOTH, Peter P.; LOTUFO, Paulo A.; BITTENCOURT, Marcio S.- Differences in HDL particle size in the presence of subclinical thyroid dysfunctions: The ELSA-Brasil study(2020) JANOVSKY, Carolina Castro Porto Silva; GENEROSO, Giuliano; GOULART, Alessandra C.; SANTOS, Raul D.; BLAHA, Michael J.; JONES, Steven; TOTH, Peter P.; LOTUFO, Paulo A.; BITTENCOURT, Marcio Sommer; BENSENOR, Isabela M.Background and aims: Thyroid dysfunction is related to several lipid abnormalities. There is no consensus about concentration of high-density lipoprotein (HDL) in different studies. The aim of this report is to evaluate HDL particle (HDL-P) subfractions across a spectrum of thyroid functions in a Brazilian population. Methods: Individuals were divided into three groups by baseline thyroid function (subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism). HDL-P subfractions were analyzed by Nuclear Magnetic Resonance (NMR) spectroscopy. To examine the association between HDL-P subfractions and thyroid function, we used univariate and multivariate linear regression models adjusted for demographic characteristics, comorbidities, lifestyle factors, and traditional lipid measurement (HDL-C, LDL-C and triglycerides). Results: Of 3304 participants, 54.1% were women, 51.2% white, with mean age 50.6 +/- 8.7 years. HDL-C and triglycerides levels (p = 0.032 and p = 0.016, respectively) were higher in the SC hypothyroid group. There were no statistically significant differences in total cholesterol levels and LDL-C levels. In univariate analysis, small HDL-P subfractions were significantly lower in subclinical hypothyroidism (p = 0.026) whereas intermediate HDL-P were higher in subclinical hyperthyroidism (p = 0.049), compared to euthyroidism. After adjustment for demographic data, SC hypothyroidism was still statistically associated with lower levels of small HDL-P. After adjusting for comorbidities, lifestyle factors, and traditional lipid measurements, SC hypothyroidism had an established association with lower levels of small HDL-P while SC hyperthyroidism was associated with lower levels of large HDL-P. Conclusions: In this large cohort from a Brazilian population, subclinical hypothyroidism was associated with lower small HDL-P subfractions, and subclinical hyperthyroidism with lower large HDL-P subfractions and higher intermediate HDL-P subfractions.