FERNANDA MARCIANO CONSOLIM COLOMBO

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Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico

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  • article 17 Citação(ões) na Scopus
    High Muscle Sympathetic Nerve Activity Is Associated With Left Ventricular Dysfunction in Treated Hypertensive Patients
    (2013) SOUZA, Silvia Beatriz Cavasin de; ROCHA, Juraci Aparecida; CUOCO, Marco Antonio Romeu; GUERRA, Grazia Maria; FERREIRA-FILHO, Julio Cesar; BORILE, Suellen; KRIEGER, Eduardo Moacyr; BORTOLOTTO, Luiz Aparecido; CONSOLIM-COLOMBO, Fernanda Marciano
    The presence of asymptomatic left ventricular diastolic dysfunction (LVDD) in hypertensive patients can be associated with the development of cardiac events. The increase in sympathetic activity may be 1 of the mechanisms that predisposes to this outcome. In this study, we analyzed 2 hypotheses: (i) whether sympathetic activity is higher in the presence of LVDD, independent of blood pressure control and (ii) whether different classes of LVDD have a different effect on sympathetic activity. After analyzing left ventricular function using echo Doppler cardiography, 45 hypertensive patients receiving treatment were allocated into 3 groups: normal function (LV-NF, n 15), impaired relaxation (LV-IR, n 15), and pseudonormal or restrictive (LV-P/R, n 15). An age-, sex-, and body mass indexmatched control group of normotensive volunteers (N, n 14) was included. Muscle sympathetic nerve activity (MSNA), heart rate, and systolic blood pressure variabilities and baroreflex sensitivity were evaluated while the patient was in a supine position. Blood pressure and antihypertensive drug use were similar among the hypertensive groups. The LV-IR and LV-P/R groups had similar MSNA (331 and 321 bursts/min, respectively), which was significantly higher than that of the LV-NF and N groups (263 and 152 bursts/min, respectively). The LV-IR and LV-P/R groups had significantly higher LF-systolic blood pressure variability and significantly lower baroreflex sensitivity compared with the N group. The presence of asymptomatic LVDD is associated with increased MSNA, independent of blood pressure control. The sympathetic hyperactivity associated with LVDD is similar in the different patterns of LVDD studied.
  • article 24 Citação(ões) na Scopus
    The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial
    (2021) SANGALETI, Carine Teles; KATAYAMA, Keyla Yukari; ANGELIS, Katia De; MORAES, Tercio Lemos de; ARAUJO, Amanda Aparecida; LOPES, Heno F.; CAMACHO, Cleber; BORTOLOTTO, Luiz Aparecido; MICHELINI, Lisete Compagno; IRIGOYEN, Maria Claudia; OLOFSSON, Peder S.; BARNABY, Douglas P.; TRACEY, Kevin J.; PAVLOV, Valentin A.; COLOMBO, Fernanda Marciano Consolim
    Background: The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS. Trial Design and Methods: The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n = 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment. Results: Galantamine treatment significantly increased antioxidant enzyme activities, including SOD [+1.65 USOD/mg protein, [95% CI 0.39-2.92], P = 0.004] and CAT [+0.93 nmol/mg, [95% CI 0.34-1.51], P = 0.01], decreased lipid peroxidation [thiobarbituric acid reactive substances [log scale 0.72 pmol/mg, [95% CI 0.46-1.07], P = 0.05], and systemic nitrite levels [log scale 0.83 mu mol/mg protein, [95% CI 0.57-1.20], P = 0.04] compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment. Conclusion: Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS.
  • article 2 Citação(ões) na Scopus
    Functional Limitation and Intermittent Claudication: Impact of Blood Pressure Measurements
    (2012) SILVA, Rita de Cassia Gengo e; GIRIBELA, Cassiana Rosa Galvao; WOLOSKER, Nelson; CONSOLIM-COLOMBO, Fernanda Marciano
    Background: Arterial hypertension is an important risk factor for Lower-Limb Occlusive Arterial Disease (LLOAD). However, the correlation between blood pressure and pulse pressure (PP) with LLOAD severity and functional impairment resulting from this disease is not well established in the Brazilian population. Objective: To verify whether there is a correlation between blood pressure, PP, LLOAD severity and functional capacity in patients with symptomatic LLOAD. Methods: A total of 65 patients (62.2 + 8.1 years, 56.9% males) were evaluated. They were divided into two groups: normal (A) and high (B) blood pressure. LLOAD severity was assessed using the ankle-brachial index (ABI) and functional capacity by the total and pain-free walking distance at the 6-minute walking test (6MWT). Results: Group A consisted of 17 (26.1%) patients. The systolic (SBP), diastolic blood pressure (DBP), and PP were, respectively, 125.4 +/- 11.7, 74.5 +/- 9.1 and 50.9 +/- 10.0 mmHg in group A and 160.7 +/- 19.6, 90.0 +/- 12.2 and 70.7 +/- 20.2 mmHg in group B. The ABI was significantly lower in group B (0.66 +/- 0.12 vs. 0.57 +/- 0.13, p < 0.05). SBP and PP correlated with LLOAD severity and the distances walked at the 6MWT. Patients with PP > 40 mmHg walked shorter distances. Conclusion: SBP and PP significantly correlated with the distances walked in the 6MWT, suggesting they are clinical markers of functional capacity impairment in patients with symptomatic LLOAD. (Arq Bras Cardiol 2012; 98(2): 161-166)
  • article 10 Citação(ões) na Scopus
    Arg16Gly and Gln27Glu beta 2 adrenergic polymorphisms influence cardiac autonomic modulation and baroreflex sensitivity in healthy young Brazilians
    (2015) ATALA, Magda M.; GOULART, Alessandra; GUERRA, Grazia M.; MOSTARDA, Cristiano; RODRIGUES, Bruno; MELLO, Priscila R.; CASARINE, Dulce E.; IRIGOYEN, Maria-Claudia; PEREIRA, Alexandre C.; CONSOLIM-COLOMBO, Fernanda M.
    The association between functional beta(2) adrenergic receptor (beta(2)-AR) polymorphisms and cardiac autonomic modulation is still unclear. Thus, two common polymorphisms in the beta(2)-AR gene (Gln27Glu beta(2) and Arg16Gly beta(2)) were studied to determine whether they might affect tonic and reflex cardiac sympathetic activity in healthy young subjects. A total of 213 healthy young white subjects of both genders (53% female), aged 18-30 years (23.5 +/- 3.4 y), had their continuous blood pressure curves noninvasively recorded by Finometer at baseline, and other hemodynamic parameters, as cardiac autonomic modulation, baroreflex sensitivity, and allele, genotype, and diplotype frequencies calculated. Associations were made between Arg16Gly beta(2) and Gln27Glu beta(2) polymorphisms and between beta(2)-AR diplotypes and all variables. The heart rate was significantly lower (P<0.001) in the presence of homozygous Arg/Arg alleles (60.9 +/- 1.5 bpm) than in that of Arg/Gly heterozygotes (65.9 +/- 1.0 bpm) or Gly/Gly homozygotes (66.3 +/- 1.2 bpm). Homozygous carriers of Arg16 allele had an alpha index (19.2 +/- 1.3) significantly higher (P<0.001) than that of the subjects with the Gly allele Gly/Gly ( 14.5 +/- 0.7) or Arg/Gly (14.6 +/- 0.7). Furthermore, the recessive Glu27Glu and the heterozygous Gln27Glu genotypes had a higher percentage of low-frequency components (LF%) than the homozygous Gln27Gln (15.1% vs. 16.0% vs. 8.2%, P=0.03, respectively). In healthy young subjects, the presence of beta(2)-AR Arg16 allele in a recessive model was associated with higher baroreflex sensitivity, and increased parasympathetic modulation in studied individuals.
  • article 15 Citação(ões) na Scopus
    Does Obstructive Sleep Apnea Influence Blood Pressure and Arterial Stiffness in Response to Antihypertensive Treatment?
    (2018) FATURETO-BORGES, Fernanda; JENNER, Raimundo; COSTA-HONG, Valeria; LOPES, Heno F.; TEIXEIRA, Sandra H.; MARUM, Elias; GIORGI, Dante A. M.; CONSOLIM-COLOMBO, Fernanda M.; BORTOLOTTO, Luiz A.; LORENZI-FILHO, Geraldo; KRIEGER, Eduardo M.; DRAGER, Luciano F.
    Untreated obstructive sleep apnea (OSA) is common in patients with hypertension and may impair blood pressure (BP) and target-organ damage responses to antihypertensive therapy. In this study, we recruited hypertensive patients who underwent treatment with a 30-day regimen of hydrochlorothiazide 25 mg plus enalapril (20 mg BID) or losartan (50 mg BID) and were assessed with a baseline clinical evaluation, polysomnography, 24-hour ambulatory BP monitoring, and carotid-femoral pulse wave velocity. All the examinations except for polysomnography were repeated at 6 and 18 months of follow-up. We studied 94 hypertensive patients (mean age, 55 +/- 9 years). The frequency of OSA was 55%. Compared with baseline, we did not observe significant differences between groups in 24-hour BP, daytime systolic and diastolic BPs, or night-time systolic BP at 6 and 18 months. The BP control rate at 24 hours (<130/80 mmHg) was similar between the groups (baseline, 42.3% versus 45.2%; 6 months, 46.9% versus 57.5%; 18 months, 66.7% versus 61.5%). However, patients with OSA had higher night-time diastolic BP decrease than did the non-OSA group (6 months, -4.9 +/- 11.8 versus -0.3 +/- 10.3 mmHg; 18 months, -6.7 +/- 11.1 versus -1.2 +/- 10.6 mmHg; P=0.027). There were no differences in the number and class of antihypertensive medications prescribed during follow-up. In terms of arterial stiffness, patients with OSA had higher pulse wave velocity than did patients without OSA at baseline (10.3 +/- 1.9 versus 9.2 +/- 1.7 m/s; P=0.024), but both groups had similar decreases in pulse wave velocity during follow-up. In conclusion, with combined antihypertensive treatment aimed at controlling BP, hypertensive patients with OSA had similar 24-hour BP and arterial stiffness to those without OSA.
  • article 40 Citação(ões) na Scopus
    Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER-Prevention Randomized Clinical Trial
    (2016) FUCHS, Sandra Costa; POLI-DE-FIGUEIREDO, Carlos E.; FIGUEIREDO NETO, Jose A.; SCALA, Luiz Cesar N.; WHELTON, Paul K.; MOSELE, Francisca; MELLO, Renato Bandeira de; VILELA-MARTIN, Jose F.; MOREIRA, Leila B.; CHAVES, Hilton; GOMES, Marco Mota; SOUSA, Marcos R. de; SILVA, Ricardo Pereira e; CASTRO, Iran; CESARINO, Evandro Jose; JARDIM, Paulo Cesar; ALVES, Joao Guilherme; STEFFENS, Andre Avelino; BRANDAO, Andrea Araujo; CONSOLIM-COLOMBO, Fernanda M.; ALENCASTRO, Paulo Ricardo de; NETO, Abrahao Afiune; NOBREGA, Antonio C.; FRANCO, Roberto Silva; SOBRAL FILHO, Dario C.; BORDIGNON, Alexandro; NOBRE, Fernando; SCHLATTER, Rosane; GUS, Miguel; FUCHS, Felipe C.; BERWANGER, Otavio; FUCHS, Flavio D.
    Background-Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER-Prevention) trial aimed to evaluate the efficacy and safety of a low-dose diuretic for the prevention of hypertension and end-organ damage. Methods and Results-This randomized, parallel, double-blind, placebo-controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new-onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38-0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm(P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow-Lyon voltage and voltage-duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). Conclusions-A combination of low-dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension.
  • article 5 Citação(ões) na Scopus
    The Role of Acute Intermittent Hypoxia in Neutrophil-Generated Superoxide, Sympathovagal Balance, and Vascular Functionin Healthy Subjects
    (2017) ALMEIDA, Germana P. L.; TROMBETTA, Ivani C.; CEPEDA, Felipe X.; HATANAKA, Elaine; CURI, Rui; MOSTARDA, Cristiano; IRIGOYEN, Maria C.; BARRETO-FILHO, Jose A. S.; KRIEGER, Eduardo M.; CONSOLIM-COLOMBO, Fernanda M.
    Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPXreoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O-2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 +/- 2 years; 22.3 +/- 0.46 kg/m(2)), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O-2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). we recorded O-2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 +/- 50 vs. 741 +/- 135, P < 0.05). We found a similar increase in LF/HF post-HPX6 (0.91 +/- 0.11 vs. 2.85 +/- 0.40, P < 0.05). PR was diminished from pre-HPX to post-HPX6 (1.0 +/- 0.03 vs. 0.85 +/- 0.06, P < 0.05). Further analysis showed significant association between O-2 saturation and PMNs RLU (R = -0.62, P = 0.02), and with LF/HF (R = -0.79, P = 0.02) post-HPX6. In addition, an association was found between PMNs RLU and PR post-HPX6 (R = 0.58, P = 0.04). Conclusion: Acute exposure to intermittent HPX not only increased superoxide generation in neutrophils, but also impaired cardiac sympathovagal balance in healthy subjects. These data reinforce the role of intermittent HPX in superoxide generation on neutrophils, which may lead to an impairment in peripheral vascular resistance.
  • article 5 Citação(ões) na Scopus
    Visceral Obesity and High Systolic Blood Pressure as the Substrate of Endothelial Dysfunction in Obese Adolescents
    (2021) HUSSID, Maria Fernanda; CEPEDA, Felipe Xerez; JORDAO, Camila P.; LOPES-VICENTE, Rafaela R. P.; VIRMONDES, Leslie; KATAYAMA, Keyla Y.; OLIVEIRA, Ezequiel F. de; OLIVEIRA, Luis V. F.; CONSOLIM-COLOMBO, Fernanda Marciano; TROMBETTA, Ivani Credidio
    Background: Obesity affects adolescence and may lead to metabolic syndrome (MetS) and endothelial dysfunction, an early marker of cardiovascular risk. Albeit obesity is strongly associated with obstructive sleep apnea (OSA), it is not clear the role of OSA in endothelial function in adolescents with obesity. Objective: To investigate whether obesity during adolescence leads to MetS and/or OSA; and causes endothelial dysfunction. In addition, we studied the possible association of MetS risk factors and apnea hypopnea index (AHI) with endothelial dysfunction. Methods: We studied 20 sedentary obese adolescents (OA; 14.2 +/- 1.6 years, 100.9 +/- 20.3kg), and 10 normal-weight adolescents (NWA, 15.2 +/- 1.2 years, 54.4 +/- 5.3kg) paired for sex. We assessed MetS risk factors (International Diabetes Federation criteria), vascular function (Flow-Mediated Dilation, FMD), functional capacity (VO(2)peak) and the presence of OSA (AHI>1event/h, by polysomnography). We considered statistically significant a P<0.05. Results: OA presented higher waist (WC), body fat, triglycerides, systolic (SBP) and diastolic blood pressure (DBP), LDL-c and lower HDL-c and VO(2)peak than NWA. MetS was presented in the 35% of OA, whereas OSA was present in 86.6% of OA and 50% of EA. There was no difference between groups in the AHI. The OA had lower FMD than NWA (6.17 +/- 2.72 vs. 9.37 +/- 2.20%, p=0.005). There was an association between FMD and WC (R=-0.506, p=0.008) and FMD and SBP (R=-0.493, p=0.006). Conclusion: In adolescents, obesity was associates with MetS and caused endothelial dysfunction. Increased WC and SBP could be involved in this alteration. OSA was observed in most adolescents, regardless of obesity.
  • article 18 Citação(ões) na Scopus
    Cardiovascular autonomic dysfunction in sickle cell anemia
    (2012) MARTINS, Wolney de Andrade; LOPES, Heno Ferreira; CONSOLIM-COLOMBO, Fernanda Marciano; GUALANDRO, Sandra de Fatima Menosi; ARTEAGA-FERNANDEZ, Edmundo; MADY, Charles
    Sickle cell anemia (SCA) is associated to increased cardiac output, normal heart rate (HR), abnormal QT dispersion and lower diastolic blood pressure (DBP). The mechanisms are still unknown. The objective of this study was to test the hypothesis that there is cardiovascular autonomic dysfunction (CAD) in SCA. The secondary objectives were to distinguish the roles of chronic anemia and hemoglobinopathy and to evaluate the predominance of the sympathetic or parasympathetic systems in the pathogenesis of CAD. Sixteen subjects with SCA, 13 with sickle cell trait (SCT), 13 with iron deficiency anemia (IDA), and 13 healthy volunteers (HV) were evaluated. All subjects were submitted to 24 h-electrocardiogram (24 h-ECG), plasma norepinephrine (NE) measurement before and after isometric exercise (IE), and also Valsalva maneuver (VM), diving maneuver (DV), and tilt test (TT). Baroreflex sensitivity (BRS) was also evaluated. The minimum, average and maximum HR as well as the percentage of bradycardia and tachycardia at 24-h ECG were similar in all groups. NE at baseline and after IE did not differ between groups. The SCA group showed less bradycardia at phase IV of VM, less bradycardia during DV, and also less tachycardia and lower DBP during TT. BRS for bradycardia and tachycardia reflex was decreased in the SCA and SCT groups. In conclusion, 1) there is CAD in SCA, and it is characterized by the reduction of BRS and the limitation of HR modulation mediated by the parasympathetic system; 2) cardiovascular sympathetic activity is preserved in SCA; and 3) hemoglobinopathy is the preponderant ethiopathogenic factor.
  • article 7 Citação(ões) na Scopus
    Relation of a Socioeconomic Index with Cognitive Function and Neuroimaging in Hypertensive Individuals
    (2021) PARADELA, Regina Silva; FERREIRA, Naomi Vidal; NUCCI, Mariana Penteado; CABELLA, Brenno; MARTINO, Luiza Menoni; TORRES, Laura Alo; COSTA, Danielle Irigoyen da; CONSOLIM-COLOMBO, Fernanda Marciano; SUEMOTO, Claudia Kimie; IRIGOYEN, Maria Claudia
    Background: Socioeconomic factors are important contributors to brain health. However, data from developing countries (where social inequalities are the most prominent) are still scarce, particularly about hypertensive individuals. Objective: To evaluate the relationship between socioeconomic index, cognitive function, and cortical brain volume, as well as determine whether white matter hyperintensities are mediators of the association of the socioeconomic index with cognitive function in hypertensive individuals. Methods: We assessed 92 hypertensive participants (mean age = 58 +/- 8.6 years, 65.2% female). Cognitive evaluation and neuroimaging were performed and clinical and sociodemographic data were collected using questionnaires. A socioeconomic index was created using education, income, occupation (manual or non-manual work), and race. The associations of the socioeconomic index with cognitive performance and brain volume were investigated using linear regression models adjusted for age, sex, time of hypertension since diagnosis, and comorbidities. A causal mediation analysis was also conducted. Results: Better socioeconomic status was associated with better visuospatial ability, executive function, and global cognition. We found associations between a better socioeconomic index and a higher parietal lobe volume. White matter hyperintensities were also not mediators in the relationship between the socioeconomic index and cognitive performance. Conclusion: Socioeconomic disadvantages are associated with worse cognitive performance and brain volume in individuals with hypertension.