Otavio Gebara

Increased Levels of C-Reactive Protein After Oral Hormone Replacement Therapy May Not Be Related to an Increased Inflammatory Response

Background—It has been suggested that hormone replacement therapy (HRT) in postmenopausal women is associated with an increased inflammatory response that may trigger acute cardiovascular events. This suggestion is mainly based on the finding of elevated C-reactive protein (CRP) levels after HRT. The aim of the present study was to evaluate a broad spectrum of vascular inflammation markers in 389 postmenopausal women with increased cardiovascular risk at baseline and after either 6 months of HRT (126 women) or no HRT (263 women). Methods and Results—Compared with baseline, CRP levels significantly increased after HRT (0.9±0.2 versus 1.6±0.4 mg/L, P <0.01); on the contrary, soluble intracellular adhesion molecule-1 decreased from 208±57 to 168±37 ng/mL (P <0.01) after HRT. Similarly, vascular cell adhesion molecule-1 decreased from 298±73 to 258±47 ng/mL (P <0.01), plasma E-selectin levels were reduced from 17.8±5.6 to 14.8±3.9 ng/mL (P <0.01), interleukin-6 levels decreased from 1.51±0.22 to 1.29±0.28 pg/mL, and s-thrombomodulin plasma levels decreased from 4.8±0.7 to 4.3±0.9 ng/mL (P <0.01). No significant changes in either CRP or vascular inflammatory marker were detected in women not taking HRT. Conclusions—The discrepancy between increased plasma levels of CRP and reduced plasma levels of all other markers of inflammation suggests that the increased CRP levels after oral HRT may be related to metabolic hepatic activation and not to an acute-phase response. HRT seems to be associated with an overall decrease in vascular inflammation.

Relationship between body mass index, waist circumference, and waist-to-hip ratio and mortality in elderly women: a 5-year follow-up study

This study examines the association between body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC) and all-cause and cardiovascular mortality in elderly women in a 5-year longitudinal study of 575 female outpatients 60 years and over. The highest BMI, WHR, and WC quartiles and predefined BMI categories were analyzed as predictive variables. Death occurred in 88 (15.4%). Underweight (BMI < 18.5 kg/m2) was associated with all-cause mortality in uni- and multivariate analyses, regardless of age bracket. The survival curves and univariate analysis showed that the highest WHR quartile (> or = 0.97) was associated with all-cause mortality. However, after adjustment for age, smoking, and previous cardiovascular diseases, the increase in WHR was positively associated only in women from 60 to 80 years of age. None of the anthropometric measurements was associated with cardiovascular mortality. The results indicate that underweight and increased waist-to-hip ratio were predictors of all-cause mortality in elderly women, mainly among those under 80 years.

Diagonal earlobe crease as a marker of the presence and extent of coronary atherosclerosis

This study evaluates the association between the presence of diagonal earlobe creases (ELC) and coronary artery disease (CAD). One thousand four hundred twenty-four patients (760 men and 664 women, aged 30 to 80 years) were examined for the presence of ELC and classified into 2 groups: group I control--1,086 consecutive patients who denied symptoms of myocardial ischemia and were admitted to a general hospital for other reasons; group II CAD--338 patients with documented CAD (presence of > or = 70% coronary diameter stenosis at angiography). ELC was present in 304 patients (28%) in group I and 220 (65%) in group II (p < 0.0001). The patients were stratified in age groups to isolate the influence of age because the prevalence of ELC and CAD increased with advancing age (p < 0.0001 for both). This association remained statistically significant in all decades, except for patients aged > 70 years. To further remove the confounding effect of different age and sex distributions between the groups, a direct adjustment of the ELC prevalence was performed. When adjusted for age and sex, the prevalence of creases was still 58% higher in patients with CAD than in control subjects (p < 0.001). The presence of ELC was also related to the extent of CAD as measured by the number of major arteries narrowed (p = 0.015). The observed sensitivity of the sign for the diagnosis of CAD was 65%, the specificity 72%, the positive predictive value 42% and the negative predictive value 87%.

Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy.

Objective: The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy. Design: We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy. Results: In all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% ± 11%, intracellular adhesion molecule: −21% ± 4%, vascular cell adhesion molecule: −15% ± 6%, E-selectin: −18% ± 4%, s-thrombomodulin −10.5% ± 3.7%, IL-6 −14% ± 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% ± 8%, intracellular adhesion molecule: −3% ± 2%, vascular cell adhesion molecule: −5% ± 2%, E-selectin: +6% ± 2%, s-thrombomodulin: +5% ± 2%, IL-6: +12% ± 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy. Conclusions: Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.

Efeitos Cardiovasculares da Testosterona

A testosterona e secretada durante tresepocas da vida: 1) no primeiro trimestre da vida intra-uterina,transitoriamente; 2) na vida neonatal e 3) continuamenteapos a puberdade. O nivel de testosterona produzido podeser calculado pela depuracao metabolica, pela media dosniveis de testosterona circulante, por diferenca arteriove-nosa testicular ou pela taxa de fluxo testicular.

Effect of a combined oral contraceptive containing 20 μg ethinyl estradiol and 75 μg gestodene on hemostatic parameters

The effects of a combined oral contraceptive (COC) containing 20 μg ethinyl estradiol (EE) and 75 μg gestodene (GSD) on prothrombin activity (PA), activated partial thromboplastin time (APTT), thrombin time (TT), platelet number, fibrinogen, antithrombin III (ATIII), protein C, protein S and D-dimer were evaluated over 6 months in 23 young, healthy women. Laboratory assessments were performed prior to initiation of COC use (pretreatment) and after 3 and 6 months of use. Results showed no significant changes in fibrinogen, protein C, ATIII or D-dimer during COC use, compared with pretreatment values. The increase in platelet count, decreases in protein S level, PA and APTT, and the prolongation of TT were significant. In conclusion, the use of a COC containing 20 μg EE and 75 μg GSD did not cause any significant changes in the hemostatic parameters studied that could be suggestive of a higher prothrombotic risk. Further studies with a larger sample size are necessary in order to obtain conclusive data.

Predictors of the risk of falls among elderly with chronic atrial fibrillation

OBJECTIVES: Though elderly persons with chronic atrial fibrillation have more comorbidities that could limit indications for the chronic use of anticoagulants, few studies have focused on the risk of falls within this particular group. To evaluate the predictors of the risk of falls among elderly with chronic atrial fibrillation, a cross-sectional, observational study was performed. METHODS: From 295 consecutive patients aged 60 years or older with a history of atrial fibrillation who were enrolled within the last 2 years in the cardiogeriatrics outpatient clinic of the Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 107 took part in this study. Their age was 77.9±6.4 years, and 62 were female. They were divided into two groups: a) no history of falls in the previous year and b) a history of one or more falls in the previous year. Data regarding the history of falls and social, demographic, anthropometric, and clinical information were collected. Multidimensional assessment instruments and questionnaires were applied. RESULTS: At least one fall was reported in 55 patients (51.4%). Among them, 27 (49.1%) presented recurrent falls, with body lesions in 90.4% and fractures in 9.1% of the cases. Multivariate logistic regression showed that self-reported difficulty maintaining balance, use of amiodarone, and diabetes were independent variables associated with the risk of falls, with a sensitivity of 92.9% and a specificity of 44.9%. CONCLUSION: In a group of elderly patients with chronic atrial fibrillation who were relatively independent and able to attend an outpatient clinic, the occurrence of falls with recurrence and clinical consequences was high. Difficulty maintaining balance, the use of amiodarone and a diagnosis of diabetes mellitus were independent predictors of the risk for falls. Thus, simple clinical data predicted falls better than objective functional tests.

Daytime systolic blood pressure load and previous stroke predict cardiovascular events in treated octogenarians with hypertension.

ACKNOWLEDGMENTS Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Yu-Wei Chen and Chih-Jen Wu: concept and design. Han-Hsiang Chen: drafting the article. Ching-Wei Chang and Tsang-En Wang: providing intellectual content of critical importance to the work described. Chen-Wang Chang: analysis and interpretation of data. Sponsor’s Role: No sponsor participated in the design, methods, subject recruitment, data collection, analysis, or preparation of the letter.

Clinical Predictors of Prognosis in Severe Aortic Stenosis in Unoperated Patients >75 Years of Age

In elderly patients with severe aortic stenosis, clinical evaluation can dictate decision making. Asymptomatic patients in normal sinus rhythm, without left atrial enlargement and without bundle branch block, can be safely followed clinically, regardless of echocardiographic findings.

Depression as a Clinical Determinant of Dependence and Low Quality of Life in Elderly Patients with Cardiovascular Disease

Background The aging process promotes a progressive increase in chronic-degenerative diseases. The effect of these diseases on the functional capacity has been well recognized. Another health parameter concerns “quality of life related to health”. Among the elderly population, cardiovascular diseases stand out due to the epidemiological and clinical impact. Usually, these diseases have been associated with others. This set of problems may compromise both independence and quality of life in elderly patients who seek cardiologic treatment. These health parameters have not been well contemplated by cardiologists. Objective Evaluating, among the elderly population with cardiovascular disease, which are the most relevant clinical determinants regarding dependence and quality of life. Methods This group was randomly and consecutively selected and four questionnaires were applied: HAQ, SF-36, PRIME-MD e Mini Mental State. Results The study included 1,020 elderly patients, 63.3% women. The group had been between 60 and 97 years-old (mean: 75.56 ± 6.62 years-old). 61.4% were independent or mild dependence. The quality of life total score was high (HAQ: 88.66 ± 2.68). 87.8% of patients had a SF-36 total score > 66. In the multivariate analysis, the association between diagnoses and high degrees of dependence was significant only for previous stroke (p = 0.014), obesity (p < 0.001), lack of physical activity (p = 0.016), osteoarthritis (p < 0.001), cognitive impairment (p < 0.001), and major depression (p < 0.001). Analyzing the quality of life, major depression and physical illness for depression was significantly associated with all domains of the SF-36. Conclusion Among an elderly outpatient cardiology population, dependence and quality of life clinical determinants are not cardiovascular comorbidities, especially the depression.