MARCIO SOMMER BITTENCOURT
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- Association Between Smoking and Serum GlycA and High-Sensitivity C-Reactive Protein Levels: The Multi-Ethnic Study of Atherosclerosis (MESA) and Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)(2017) KIANOUSH, Sina; BITTENCOURT, Marcio S.; LOTUFO, Paulo A.; BENSENOR, Isabela M.; JONES, Steven R.; DEFILIPPIS, Andrew P.; TOTH, Peter P.; OTVOS, James D.; TIBUAKUU, Martin; HALL, Michael E.; HARADA, Paulo H. N.; BLAHA, Michael J.Background-Inflammation is suggested to be a central feature of atherosclerosis, particularly among smokers. We studied whether inflammatory biomarkers GlycA and high-sensitivity C-reactive protein are associated with cigarette smoking. Methods and Results-A total of 11 509 participants, 6774 from the MESA (Multi-Ethnic Study of Atherosclerosis) and 4735 from ELSA-Brasil (The Brazilian Longitudinal Study of Adult Health) were included. We evaluated the cross-sectional association between multiple measures of smoking behavior and the inflammatory biomarkers, GlycA and high-sensitivity C-reactive protein, using regression models adjusted for demographic, anthropometric, and clinical characteristics. Participants were 57.7 +/- 11.1 years old and 46.4% were men. Never, former, and current smokers comprised 51.7%, 34.0%, and 14.3% of the population, respectively. Multivariable-adjusted mean absolute difference in GlycA levels (mu mol/L) with 95% confidence interval (CI) were higher for former (4.1, 95% CI, 1.7-6.6 mu mol/L) and current smokers (19.9, 95% CI, 16.6-23.2 mu mol/L), compared with never smokers. Each 5-unit increase in pack-years of smoking was associated with higher GlycA levels among former (0.7, 95% CI, 0.3-1.1 mu mol/L) and current smokers (1.6, 95% CI, 0.8-2.4 mu mol/L). Among former smokers, each 5-year increase in time since quitting smoking was associated with lower GlycA levels (-1.6, 95% CI, -2.4 to -0.8 lmol/L) and each 10-unit increase in number of cigarettes/day was associated with higher GlycA among current smokers (2.8, 95% CI, 0.5-5.2 mu mol/L). There were similar significant associations between all measures of smoking behavior, and both log-transformed GlycA and high-sensitivity C-reactive protein. Conclusions-Acute and chronic exposure to tobacco smoking is associated with inflammation, as quantified by both GlycA and high-sensitivity C-reactive protein. These biomarkers may have utility for the study and regulation of novel and traditional tobacco products.
- Race and Resting-State Heart Rate Variability in Brazilian Civil Servants and the Mediating Effects of Discrimination: An ELSA-Brasil Cohort Study(2016) KEMP, Andrew H.; KOENIG, Julian; THAYER, Julian F.; BITTENCOURT, Marcio S.; PEREIRA, Alexandre C.; SANTOS, Itamar S.; DANTAS, Eduardo M.; MILL, Jose G.; CHOR, Dora; RIBEIRO, Antonio L. P.; BENSENOR, Isabela M.; LOTUFO, Paulo A.Objectives African Americans are characterized by higher heart rate variability (HRV), a finding ostensibly associated with beneficial health outcomes. However, these findings are at odds with other evidence that blacks have worse cardiovascular outcomes. Here, we examine associations in a large cohort from the ELSA-Brasil study and determined whether these effects are mediated by discrimination. Methods Three groups were compared on the basis of self-declared race: black (n = 2,020), brown (n = 3,502), and white (n = 6,467). Perceived discrimination was measured using a modified version of the Everyday Discrimination Scale. Resting-state HRV was extracted from 10-minute resting-state electrocardiograms. Racial differences in HRV were determined by regression analyses weighted by propensity scores, which controlled for potentially confounding variables including age, sex, education, and other health-related information. Nonlinear mediation analysis quantified the average total effect, comprising direct (race-HRV) and indirect (race-discrimination-HRV) pathways. Results Black participants displayed higher HRV relative to brown (Cohen's d = 0.20) and white participants (Cohen's d = 0.31). Brown relative to white participants also displayed a small but significantly higher HRV (Cohen's d = 0.14). Discrimination indirectly contributed to the effects of race on HRV. Conclusions This large cohort from the Brazilian population shows that HRV is greatest in black, followed by brown, relative to white participants. The presence of higher HRV in these groups may reflect a sustained compensatory psychophysiological response to the adverse effects of discrimination. Additional research is needed to determine the health consequences of these differences in HRV across racial and ethnic groups.
- Subclinical carotid artery atherosclerosis and performance on cognitive tests in middle-aged adults: Baseline results from the ELSA-Brasil(2015) SUEMOTO, Claudia K.; SANTOS, Itamar S.; BITTENCOURT, Marcio S.; PEREIRA, Alexandre C.; GOULART, Alessandra C.; RUNDEK, Tatjana; PASSOS, Valeria M.; LOTUFO, Paulo; BENSENOR, Isabela M.Background and aims: Carotid artery intima-media thickness (CIMT) may be used as a biomarker for early cognitive impairment. However, the results of the association between CIMT and cognitive function in middle-aged subjects are mixed. We aimed to investigate this association in a large Brazilian sample with no history of stroke at baseline. Additionally, we tested the effect of interactions between CIMT and cardiovascular risk factors on cognitive performance. Methods: In this cross-sectional study, cognition was evaluated using the delayed word recall (DWRT), the category fluency, and the trail making tests (TMT). CIMT was measured at the common carotid artery. The association between CIMT and cognitive tests was investigated using linear regression models, adjusted for an extensive set of possible confounding variables. We also included interaction terms with selected risk factors. Results: The mean age of the 8208 participants was 49.6 +/- 7.3 years, 44% were male, and 56% White. Increase in CIMT was associated with worse performance on the DWRT (beta = -0.433, 95% CI = -0.724; -0.142, p = 0.004). We found effect modification of the association between cognitive function and CMIT by self-reported heart failure and alcohol intake. Participants had worse performance in the TMT if they had greater CIMT and current alcohol use (p < 0.0001). The interaction between CIMT and heart failure on TMT performance was not significant after adjustment for multiple comparisons (p = 0.07). Conclusions: In this sample of middle-aged adults, CIMT was inversely associated with memory function. Additionally, the presence of alcohol use resulted in a stronger association of CIMT with worse performance on an executive function test.
conferenceObject Anxiety and Depressive Symptoms are Associated with Coronary Artery Calcium. A Cross-sectional Analysis of Elsa-Brasil Baseline Data(2016) SANTOS, Itamar S.; BITTENCOURT, Marcio S.; ROCCO, Priscila T.; PEREIRA, Alexandre C.; BARRETO, Sandhi M.; BRUNONI, Andre R.; GOULART, Alessandra C.; BLAHA, Michael J.; LOTUFO, Paulo A.; BENSENOR, Isabela M.- Impact of metabolically healthy obesity on carotid intima-media thickness - The Brazilian Longitudinal Study of Adult Health(2020) ROMAGNOLLI, Carla; BENSENOR, Isabela M.; SANTOS, Itamar S.; LOTUFO, Paulo A.; BITTENCOURT, Marcio S.Background and aims: Obesity increases the risk of metabolic abnormalities, which contributes to elevated cardiovascular risk. However, the independent role of obesity in the development of cardiovascular disease is still debatable. There are individuals with an obesity phenotype without metabolic abnormalities: ""metabolically healthy obesity"" (MHO). This study evaluates the association between MHO and carotid intima-media thickness (CIMT), an early marker of subclinical atherosclerosis. Methods and results: This is a cross-sectional analysis of the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We used a strict definition to classify MHO: body mass index >30 kg/m2 and meeting none of the four metabolic syndrome criteria. Data from 10,335 participants were analyzed. The obesity prevalence in our population was 21.2% (n = 2191). The prevalence of MHO was 5.6% (n = 124). When individuals were stratified according to metabolic health, we found the metabolically healthy individuals were younger, more likely to be women and never smokers. The mean CIMT of the sample was 0.81 mm (+0.20). The mean CIMT of the metabolically healthy subsample was 0.70 mm (+0.13) in individuals without obesity and 0.76 mm (+0.13) in individuals with obesity (p < 0.001). The mean CIMT of the metabolically unhealthy subsample was 0.81 mm (+0.20) in individuals without obesity and 0.88 mm (+0.20) in individuals with obesity (p <0.001). These findings remained essentially unchanged after multivariate adjustment for confounding factors. Conclusion: The concept of MHO, even with the strict definition, seems inadequate, as even in this population, obesity is associated with higher CIMT levels.
- Whole-genome sequencing uncovers two loci for coronary artery calcification and identifies ARSE as a regulator of vascular calcification(2023) VRIES, Paul S. de; CONOMOS, Matthew P.; SINGH, Kuldeep; NICHOLSON, Christopher J.; JAIN, Deepti; HASBANI, Natalie R.; JIANG, Wanlin; LEE, Sujin; CARDENAS, Christian L. Lino; LUTZ, Sharon M.; WONG, Doris; GUO, Xiuqing; YAO, Jie; YOUNG, Erica P.; TCHEANDJIEU, Catherine; HILLIARD, Austin T.; BIS, Joshua C.; BIELAK, Lawrence F.; BROWN, Michael R.; MUSHAROFF, Shaila; CLARKE, Shoa L.; TERRY, James G.; PALMER, Nicholette D.; YANEK, Lisa R.; XU, Huichun; HEARD-COSTA, Nancy; WESSEL, Jennifer; SELVARAJ, Margaret Sunitha; LI, Rebecca H.; SUN, Xiao; TURNER, Adam W.; STILP, Adrienne M.; KHAN, Alyna; NEWMAN, Anne B.; RASHEED, Asif; FREEDMAN, Barry I.; KRAL, Brian G.; MCHUGH, Caitlin P.; HODONSKY, Chani; SALEHEEN, Danish; HERRINGTON, David M.; JACOBS JR., David R.; NICKERSON, Deborah A.; BOERWINKLE, Eric; WANG, Fei Fei; HEISS, Gerardo; JUN, Goo; KINNEY, Greg L.; SIGURSLID, Haakon H.; DODDAPANENI, Harshavardhan; HALL, Ira M.; BENSENOR, Isabela M.; BROOME, Jai; CRAPO, James D.; WILSON, James G.; SMITH, Jennifer A.; BLANGERO, John; VARGAS, Jose D.; MOSQUERA, Jose Verdezoto; SMITH, Joshua D.; VIAUD-MARTINEZ, Karine A.; RYAN, Kathleen A.; YOUNG, Kendra A.; TAYLOR, Kent D.; LANGE, Leslie A.; EMERY, Leslie S.; BITTENCOURT, Marcio S.; BUDOFF, Matthew J.; MONTASSER, May E.; YU, Miao; MAHANEY, Michael C.; MAHAMDEH, Mohammed S.; FORNAGE, Myriam; FRANCESCHINI, Nora; LOTUFO, Paulo A.; NATARAJAN, Pradeep; WONG, Quenna; MATHIAS, Rasika A.; GIBBS, Richard A.; DO, Ron; MEHRAN, Roxana; TRACY, Russell P.; KIM, Ryan W.; NELSON, Sarah C.; DAMRAUER, Scott M.; KARDIA, Sharon L. R.; RICH, Stephen S.; FUSTER, Valentin; NAPOLIONI, Valerio; ZHAO, Wei; TIAN, Wenjie; YIN, Xianyong; I, Yuan- Min; MANNING, Alisa K.; PELOSO, Gina; KELLY, Tanika N.; O'DONNELL, Christopher J.; MORRISON, Alanna C.; CURRAN, Joanne E.; ZAPOL, Warren M.; BOWDEN, Donald W.; BECKER, Lewis C.; CORREA, Adolfo; MITCHELL, Braxton D.; PSATY, Bruce M.; CARR, John Jeffrey; PEREIRA, Alexandre C.; ASSIMES, Themistocles L.; STITZIEL, Nathan O.; HOKANSON, John E.; LAURIE, Cecelia A.; ROTTER, Jerome I.; VASAN, Ramachandran S.; POST, Wendy S.; PEYSER, Patricia A.; MILLER, Clint L.; MALHOTRA, RajeevCoronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study of CAC in 22,400 participants from multiple ancestral groups. We confirmed associations with four known loci and identified two additional loci associated with CAC (ARSE and MMP16), with evidence of significant associations in replication analyses for both novel loci. Functional assays of ARSE and MMP16 in human vascular smooth muscle cells (VSMCs) demonstrate that ARSE is a promoter of VSMC calcification and VSMC phenotype switching from a contractile to a calcifying or osteogenic phenotype. Furthermore, we show that the association of variants near ARSE with reduced CAC is likely explained by reduced ARSE expression with the G allele of enhancer variant rs5982944. Our study highlights ARSE as an important contributor to atherosclerotic vascular calcification and a potential drug target for vascular calcific disease. de Vries, Conomos, Singh and Nicholson et al. identify two additional loci associated with coronary artery calcification (ARSE and MMP16) via a genome-wide association study in 22,400 participants from multiple ancestral groups and prove that ARSE is a mediator of vascular smooth muscle cell calcification and phenotype switching.
- Relationship between TSH Levels and the Advanced Lipoprotein Profile in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)(2020) MIRANDA, Erique Jose F. Peixoto de; GOULART, Alessandra C.; BITTENCOURT, Matti Sommer; SANTOS, Raul D.; BLAHA, Michael J.; JONES, Steven; TOTH, Peter P.; KULKARNI, Krishnaji; SANTOS, Itamar S.; LOTUFO, Paulo A.; BENSENOR, Isabela M.Purpose/aims: The relationship between thyroid-stimulating hormone (TSH) and lipoprotein subfractions by Vertical Auto Profile (VAP) is unclear. We aimed to evaluate lipoprotein profiles according to TSH levels in euthyroid individuals.Material and Methods: Cross-sectional analysis of 3,525 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) with no previous thyroid disease and who were not on lipid-lowering medication. Total-cholesterol and its fractions, lipoprotein subfractions, triglycerides, and triglyceride-rich lipoprotein cholesterol [TRL-C (VLDL1+2-C, VLDL3-C, IDL-C)] were determined by VAP. Associations between TSH quintiles and lipoprotein subfractions were evaluated by crude and adjusted linear regression models.Results: For the total sample, significant beta-coefficients in full adjusted models for the 5(th) quintile of TSH (compared to 1(st)) were found for the following VAP lipids and lipoproteins: IDL-C (beta: 0.90; 0.11 to 1.69); VLDL-C (beta: 2.80; 1.51 to 4.08), triglycerides (beta: 18.66; 8.07 to 29.25), non-HDL-C (beta: 4.63; 0.50 to 8.75 mg/dl), TRL-C (beta:1.93;0.70 to 3.17), VLDL3-C (beta: 1.04; 0.50 to 1.57), as well as, TC/HDL-C (beta: 0.15; 0.03 to 0.26) and TG/HDL-C ratio (beta: 0.49;0.21 to 0.77). In women, similar results were found for VLDL-C, triglycerides, non-HDL-C, TRL-C, VLDL3-C, TC/HDL-C and TG/HDL-C-ratios. In men, we also found positive associations between the highest quintile of TSH with VLDL-C, triglycerides, VLDL3-C and TG/HDL-C.Conclusions: In the ELSA-Brasil, the highest TSH levels were mostly positively associated with lipoprotein levels, particularly TG, TRL and their remnants. Notwithstanding, our findings suggest that TSH levels within the normal range have little impact on the atherogenic profile.
- 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.
- Association of Carotid Plaques and Common Carotid Intima-media Thickness with Modifiable Cardiovascular Risk Factors(2021) SANTOS-NETO, Pedro J.; SENA-SANTOS, Eduardo H.; MEIRELES, Danilo P.; BITTENCOURT, Marcio Sommer; SANTOS, Itamar S.; BENSENOR, Isabela M.; LOTUFO, Paulo A.Objective: To assess the association of carotid plaques and common carotid artery intimamedia thickness with traditional modifiable cardiovascular risk factors. Methods: We examined 4,266 participants aged 35-74years in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline. The presence of plaques at all carotid arteries sites was evaluated. The mean far wall common carotid artery intima-media thickness was measured. To evaluate the association of cardiovascular risk factors with plaques and plaque burden, we applied logistic regression models presented as crude, adjusted by sociodemographic variables, along with multivariate further adjustment for hypertension, diabetes, hypercholesterolemia, and smoking. For the association of cardiovascular risk factors and common carotid artery intima-media thickness, linear regression models were used with the same adjustments. Results: Median age was 51 years (interquartile range: 45-58 years; 54.5% of females). Plaque prevalence in at least one segment of the carotid arteries was 35.9%. Mean common carotid artery intima-media thickness of the far walls was 0.609 +/- 0.133 mm. In the multivariate model for plaque presence, the odds ratios were:1.39 (1.19-1.63) for hypertension;1.58 (1.36-1.82) for hypercholesterolemia; 2.00 (1.65-2.43),1.19 (1.02-1.40) for current and past smoking, and 1.13 (0.95-1.35) for diabetes. In the multivariate linear regression models, common carotid artery intimamedia thickness beta-coefficients were: 0.035 mm (0.027-0.043) for hypertension; 0.020 mm (0.013-0.027) for hypercholesterolemia; 0.020 mm (0.010-0.029), 0.012 mm (0.004-0.020) for current and past smoking, and 0.024 mm (0.015-0.033) for diabetes. Conclusion: Cardiovascular risk factors were independently associated with increasing common carotid artery intima-media thickness, plaque prevalence, and plaque scores. Diabetes did not show an independent association with plaques in the multivariate model.
- Association of Lipoprotein Subfractions With Atherosclerosis in the Baseline Sample of ELSA-Brasil Cohort Study - A Cross-Sectional Analysis(2023) TEBAR, William R.; MENEGHINI, Vandrize; GOULART, Alessandra C.; SANTOS, Itamar S.; SANTOS, Raul D.; BITTENCOURT, Marcio S.; GENEROSO, Giuliano; PEREIRA, Alexandre; BLAHA, Michael J.; JONES, Steven R.; TOTH, Peter P.; OTVOS, James D.; LOTUFO, Paulo A.; BENSENOR, Isabela M.