Silent Atrial Fibrillation in Elderly Pacemaker Users: A Randomized Trial Using Home Monitoring.

BACKGROUND: Pacemaker with remote monitoring (PRM) may be useful for silent atrial fibrillation (AF) detection. The aims of this study were to evaluate the incidence of silent AF, the role of PRM, and to determine predictors of silent AF occurrence. METHODS: Three hundred elderly patients with permanent pacemaker (PPM) were randomly assigned to the remote group (RG) or control group (CG). All patients received PPM with remote monitoring capabilities. Primary end point was AF occurrence rate and the secondary end points were time to AF detection and number of days with AF. RESULTS: During the average follow-up of 15.7±7.7 months, AF episodes were detected in 21.6% (RG = 24% vs CG = 19.3%, P = 0.36]. There was no difference in the time to detect the first AF episode. However, the median time to detect AF recurrence in the RG was lower than that in the CG (54 days vs 100 days, P = 0.004). The average number of days with AF was 16.0 and 51.2 in the RG and CG, respectively (P = 0.028). Predictors of silent AF were left atrial diameter (odds ratio [OR] 1.2; 95% CI = 1.1-1.3; P < 0.001) and diastolic dysfunction (OR 4.8; 95% CI = 1.6-14.0; P = 0.005). CONCLUSIONS: The incidence of silent AF is high in elderly patients with pacemaker; left atrial diameter and diastolic dysfunction were predictors of its occurrence. AF monitoring by means of pacemaker is a valuable tool for silent AF detection and continuous remote monitoring allows early AF recurrence detection and reduces the number of days with AF.

Minimally supervised multimodal exercise to reduce falls risk in economically and educationally disadvantaged older adults.

Few studies have evaluated the benefit of providing exercise to underprivileged older adults at risk for falls. Economically and educationally disadvantaged older adults with previous falls (mean age 79.06, SD = 4.55) were randomized to 4 mo of multimodal exercise provided as fully supervised center-based (FS, n = 45), minimally supervised home-based (MS, n = 42), or to nonexercise controls (C, n = 32). Comparing groups on the mean change in fall-relevant mobility task performance between baseline and 4 mo and compared with the change in C, both FS and MS had significantly greater reduction in timed up-and-go, F(2,73) = 5.82, p = .004, η2 p = .14, and increase in tandem-walk speed, F(2,73) = 7.71, p < .001 η2 p = .17. Change in performance did not statistically differ between FS and MS. In community-dwelling economically and educationally disadvantaged older adults with a history of falls, minimally supervised home-based and fully supervised center-based exercise programs may be equally effective in improving fall-relevant functional mobility.

How to Improve Clinical Outcomes and Reduce Cardiovascular Risk in Older People with Cardiovascular Disease: Bridging Evidence Gaps.

The geriatric population is greatly impacted by cardiovascular disease. Thus, it becomes essential to 'geriatricise' the cardiologist through the dissemination of geriatric cardiology. In the early days of geriatric cardiology, it was discussed whether it was simply cardiology 'well done'. Today, 40 years later, it seems clear that this is indeed the case. Patients with cardiovascular disease usually have several chronic conditions. Clinical practice guidelines often address a single condition and do not provide sufficient guidance for patients with multimorbidity. There are several evidence gaps regarding these patients. Physicians and members ofthe care team need a multidimensional understanding ofthe patient to better promote the optimisation of care. It is important to understand that ageing is inevitable, heterogeneous and increases vulnerability. Caregivers must know how to assess elderly patients in a multidomain practical way and how to recognise the factors that may have implications on treatment.

Inflammatory and Immunological parameters in adults with Down syndrome.

BACKGROUND: The increase in life expectancy within the general population has resulted in an increasing number of elderly adults, including patients with Down syndrome (DS), with a current life expectancy of about 50 years. We evaluate the parameters of humoral and cellular immune response, the quantitative expression of the regulator of calcineurin1 gene (RCAN1) and the production of cytokines. The study group consisted of adults DS (n = 24) and a control group with intellectual disability without Down syndrome (ID) (n = 21) and living in a similar environmental background. It was evaluated serology, immunophenotyping, the quantitative gene expression of RCAN1 and the production of cytokines. RESULTS: In the DS group, the results showed an increase in NK cells, CD8, decreased CD19 (p < 0.05) and an increase spontaneous production of IFNgamma, TNFalpha and IL-10 (p < 0.05). There was not any difference in RCAN1 gene expression between the groups. CONCLUSIONS: These data suggest a similar humoral response in the two groups. The immunophenotyping suggests sign of premature aging of the immune system and the cytokine production show a proinflammatory profile.

Short- and Midterm Adherence to Platelet P2Y12 Receptor Inhibitors After Percutaneous Coronary Intervention With Drug-Eluting Stents.

INTRODUCTION/OBJECTIVES: In patients who have undergone recent percutaneous coronary intervention (PCI), poor adhesion to antiplatelet agents may increase the risk of stent thrombosis and death. We aimed to investigate the adherence to different P2Y12 receptor inhibitors after PCI with drug-eluting stent in stable and unstable patients and to evaluate the factors associated with low adherence. METHOD: In a prospective study conducted between 2014 and 2018, the 8-item Morisky scale was applied at 30 days and 6 months post-PCI to measure P2Y12 receptor inhibitors adherence. Also, we describe the characteristics of patients using different platelet receptor P2Y12 inhibitors. Regression models were used to identify predictors of poor adherence. RESULTS: A total of 214 patients were included (65 ± 12 years, 81% man, 61% acute coronary syndromes). Patients in the clopidogrel group were older than those in the prasugrel (68 ± 12 vs 59 ± 11 years, P < .01, respectively) or ticagrelor group (68 ± 12 vs 62 ± 12 years, P < .01). Patients with low/moderate adherence at 30 days and 6 months represented, respectively, 19.8% and 27.5% of our sample. Current smokers and preexisting cardiovascular disease at presentation were associated with lower adherence at 30 days. CONCLUSIONS: We found substantial rates of moderate and low adherence to P2Y12 receptor inhibitors early after PCI. Current smokers and preexisting cardiovascular disease at presentation were associated with a lower likelihood of adherence. These results highlight the need of monitoring adherence to medical treatment after PCI.

Hypertension and Stroke: Update on Treatment.

Stroke is the second most common cause of mortality worldwide and the third most common cause of disability. Hypertension is the most prevalent risk factor for stroke. Stroke causes and haemodynamic consequences are heterogeneous which makes the management of blood pressure in stroke patients complex requiring an accurate diagnosis and precise definition of therapeutic goals. In this article, the authors provide an updated review on the management of arterial hypertension to prevent the first episode and the recurrence. They also present a discussion on blood pressure management in hypertensive urgencies and emergencies, especially in the acute phase of hypertensive encephalopathy, ischaemic stroke and haemorrhagic stroke.

Association between clinical factors and self-underestimation of cardiovascular risk in subjects submitted to a routine health evaluation.

BACKGROUND: The perception of cardiovascular (CV) risk is essential for adoption of healthy behaviors. However, subjects underestimate their own risk. HYPOTHESIS: Clinical characteristics might be associated with self-underestimation of CV risk. METHODS: This is a retrospective, cross-sectional study of individuals submitted to routine health evaluation between 2006 and 2012, with calculated lifetime risk score (LRS) indicating intermediate or high risk for CV disease (CVD). Self-perception of risk was compared with LRS. Logistic regression analysis was performed to test the association between clinical characteristics and subjective underestimation of CV risk. RESULTS: Data from 5863 subjects (age 49.4 ± 7.1 years; 19.9% female) were collected for analysis. The LRS indicated an intermediate risk for CVD in 45.7% and a high risk in 54.3% of individuals. The self-perception of CV risk was underestimated compared with the LRS in 4918 (83.9%) subjects. In the adjusted logistic regression model, age (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.10-1.47 per 10 years, P = 0.001), smoking (OR: 1.99, 95% CI: 1.40-2.83, P < 0.001), dyslipidemia (OR: 1.21, 95% CI: 1.01-1.46, P = 0.045), physical activity (OR: 1.66, 95% CI: 1.36-2.02, P < 0.001), and use of antihypertensive (OR: 1.49, 95% CI: 1.15-1.92, P = 0.002) and lipid-lowering medications (OR: 2.13, 95% CI: 1.56-2.91, P < 0.001) were associated with higher chance of risk underestimation, whereas higher body mass index (OR: 0.92, 95% CI: 0.90-0.94, P < 0.001), depressive symptoms (OR: 0.46, 95% CI: 0.37-0.57, P < 0.001), and stress (OR: 0.41, 95% CI: 0.33-0.50, P < 0.001) decreased the chance. CONCLUSIONS: Among individuals submitted to routine medical evaluation, aging, smoking, dyslipidemia, physical activity, and use of antihypertensive and lipid-lowering medications were associated with higher chance of CV risk underestimation. Subjects with these characteristics may benefit from a more careful risk orientation.

High frequency of silent brain infarcts associated with cognitive deficits in an economically disadvantaged population.

OBJECTIVE:: Using magnetic resonance imaging, we aimed to assess the presence of silent brain vascular lesions in a sample of apparently healthy elderly individuals who were recruited from an economically disadvantaged urban region (São Paulo, Brazil). We also wished to investigate whether the findings were associated with worse cognitive performance. METHODS:: A sample of 250 elderly subjects (66-75 years) without dementia or neuropsychiatric disorders were recruited from predefined census sectors of an economically disadvantaged area of Sao Paulo and received structural magnetic resonance imaging scans and cognitive testing. A high proportion of individuals had very low levels of education (4 years or less, n=185; 21 with no formal education). RESULTS:: The prevalence of at least one silent vascular-related cortical or subcortical lesion was 22.8% (95% confidence interval, 17.7-28.5), and the basal ganglia was the most frequently affected site (63.14% of cases). The subgroup with brain infarcts presented significantly lower levels of education than the subgroup with no brain lesions as well as significantly worse current performance in cognitive test domains, including memory and attention (p<0.002). CONCLUSIONS:: Silent brain infarcts were present at a substantially high frequency in our elderly sample from an economically disadvantaged urban region and were significantly more prevalent in subjects with lower levels of education. Covert cerebrovascular disease significantly contributes to cognitive deficits, and in the absence of magnetic resonance imaging data, this cognitive impairment may be considered simply related to ageing. Emphatic attention should be paid to potentially deleterious effects of vascular brain lesions in poorly educated elderly individuals from economically disadvantaged environments.

Persistent Depressive Symptoms are Independent Predictors of Low-Grade Inflammation Onset Among Healthy Individuals.

Background: Depressive symptoms are independently associated with an increased risk of cardiovascular disease (CVD) among individuals with non-diagnosed CVD. The mechanisms underlying this association, however, remain unclear. Inflammation has been indicated as a possible mechanistic link between depression and CVD. Objectives: This study evaluated the association between persistent depressive symptoms and the onset of low-grade inflammation. Methods: From a database of 1,508 young (mean age: 41 years) individuals with no CVD diagnosis who underwent at least two routine health evaluations, 134 had persistent depressive symptoms (Beck Depression Inventory - BDI ≥ 10, BDI+) and 1,374 had negative symptoms at both time points (BDI-). All participants had been submitted to repeated clinical and laboratory evaluations at a regular follow-up with an average of 26 months from baseline. Low-grade inflammation was defined as plasma high-sensitivity C-Reactive Protein (CRP) concentrations > 3 mg/L. The outcome was the incidence of low-grade inflammation evaluated by the time of the second clinical evaluation. Results: The incidence of low-grade inflammation was more frequently observed in the BDI+ group compared to the BDI- group (20.9% vs. 11.4%; p = 0.001). After adjusting for sex, age, waist circumference, body mass index, levels of physical activity, smoking, and prevalence of metabolic syndrome, persistent depressive symptoms remained an independent predictor of low-grade inflammation onset (OR = 1.76; 95% CI: 1.03-3.02; p = 0.04). Conclusions: Persistent depressive symptoms were independently associated with low-grade inflammation onset among healthy individuals.

Fundamento: Sintomas depressivos estão associados de forma independente ao risco aumentado de doença cardiovascular (DCV) em indivíduos com DCV não diagnosticada. Os mecanismos subjacentes a essa associação, entretanto, não estão claros. Inflamação tem sido indicada como um possível elo mecanicista entre depressão e DCV. Objetivos: Este estudo avaliou a associação entre sintomas depressivos persistentes e o início de inflamação de baixo grau. Métodos: De um banco de dados de 1.508 indivíduos jovens (idade média: 41 anos) sem diagnóstico de DCV submetidos a pelo menos duas avaliações de saúde de rotina, 134 tinham sintomas depressivos persistentes (Inventário de Depressão de Beck - BDI ≥10, BDI+) e 1.374 não apresentavam sintomas em nenhuma das ocasiões (BDI-). Todos os participantes foram submetidos a repetidas avaliações clínicas e laboratoriais em seguimento regular, cuja média foi de 26 meses desde a condição basal. Definiu-se inflamação de baixo grau como concentração plasmática de proteína C reativa (PCR) ultrassensível > 3 mg/L. O desfecho foi a incidência de inflamação de baixo grau por ocasião da segunda avaliação clínica. Resultados: A incidência de inflamação de baixo grau foi maior no grupo BDI+ em comparação ao grupo BDI- (20,9% vs. 11,4%; p = 0,001). Após ajuste para sexo, idade, circunferência abdominal, índice de massa corporal, níveis de atividade física, tabagismo e prevalência de síndrome metabólica, os sintomas depressivos persistentes continuaram sendo um preditor independente de início de inflamação de baixo grau (OR = 1,76; IC 95%: 1,03-3,02; p = 0,04). Conclusões: Sintomas depressivos persistentes foram independentemente associados com início de inflamação de baixo grau em indivíduos saudáveis.

Prefrontal-Parietal White Matter Volumes in Healthy Elderlies Are Decreased in Proportion to the Degree of Cardiovascular Risk and Related to Inhibitory Control Deficits.

Cardiovascular risk (CVR) factors may be associated with poor cognitive functioning in elderlies and impairments in brain structure. Using MRI and voxel-based morphometry (VBM), we assessed regional white matter (WM) volumes in a population-based sample of individuals aged 65-75 years (n = 156), subdivided in three CVR subgroups using the Framingham Risk Score. Cognition was assessed using the Short Cognitive Performance Test. In high-risk subjects, we detected significantly reduced WM volume in the right juxtacortical dorsolateral prefrontal region compared to both low and intermediate CVR subgroups. Findings remained significant after accounting for the presence of the APOEε4 allele. Inhibitory control performance was negatively related to right prefrontal WM volume, proportionally to the degree of CVR. Significantly reduced deep parietal WM was also detected bilaterally in the high CVR subgroup. This is the first large study documenting the topography of CVR-related WM brain volume deficits. The significant association regarding poor response inhibition indicates that prefrontal WM deficits related to CVR are clinically meaningful, since inhibitory control is known to rely on prefrontal integrity.

Estrogen treatment improves arterial distensibility, fibrinolysis, and metabolic profile in postmenopausal women with type 2 diabetes mellitus.

The effects of isolated estrogen therapy on the hemostatic system and arterial distensibility were determined in postmenopausal females with type 2 diabetes mellitus. This was a prospective nonrandomized study of 19 subjects (age, 56.2 +/- 4.7 years; body mass index, 27.8 +/- 2.4 kg/m(2) [mean +/- SD]). Inclusion was done after 2 months of glycemic and blood pressure control. The study consisted of 4 months of placebo treatment immediately followed by an equal period of oral conjugated equine estrogens (CEE) 0.625 mg/d. Measures included anthropometrics, a metabolic profile (oral glucose tolerance test and fasting glycated hemoglobin, total cholesterol and fractions, and triglyceride levels), and coagulation and fibrinolytic factors at the end of the placebo period and after 4 months of oral CEE. Conjugated equine estrogen therapy decreased plasminogen activator inhibitor 1 (placebo x CEE: 16.33 +/- 9.11 x 13.08 +/- 8.87 UI/mL, P < .03) and increased factor VIII activity (134.11% +/- 46.18% x 145.33% +/- 42.04%, P < .04). An increase in high-density lipoprotein cholesterol levels (placebo x CEE: 42.47 +/- 6.80 x 53.32 +/- 11.89 mg/dL, P < .01), and a decrease in glycated hemoglobin (8.45% +/- 1.30% vs 7.58% +/- 1.06%, P < .02) and in fasting glucose levels (121.51 +/- 21.05 x 111.21 +/- 20.74 mg/dL, P = .02) followed CEE therapy. Pulse wave velocity and augmentation index were performed by applanation tonometry and were obtained at the end of the placebo period (placebo), again after an intravenous load of 1.25 mg of CEE (short-term), and after 4 months of oral CEE (long-term). A significant decrease in central (carotid-femoral) pulse wave velocity was seen both after short- and long-term CEE (placebo vs short-term vs long-term: 9.36 +/- 2.58 vs 8.26 +/- 2.20 vs 7.98 +/- 1.90 m/s, respectively [analysis of variance, P < .03]; placebo vs short-term, P < .05; placebo vs long-term, P < .01), whereas augmentation index decreased only after long-term CEE (placebo vs short-term vs long-term: 39.14% +/- 6.94% vs 37.48% +/- 8.67% vs 34.3.3% +/- 8.11% [analysis of variance, P < .05], respectively; placebo vs long-term, P < .05). Long-term administration of CEE leads to an improvement in fibrinolysis and arterial distensibility, associated with an increase of the intrinsic coagulation pathway in postmenopausal women with type 2 diabetes mellitus.

Effect of estradiol 17beta upon coronary artery vasoconstrictor response to methylergometrine maleate in female menopausal patients.

BACKGROUND: Estrogens produce several beneficial effects upon the cardiovascular system. Amongst these, an endothelium-independent effect has been convincingly demonstrated only in vitro, while there is no evidence for such an effect in vivo. The aim of the present study was to evaluate the effect of acute administration of estradiol 17beta upon coronary artery reactivity to methylergometrine in 16 menopausal patients with coronary artery disease. METHODS: Sixteen menopausal patients underwent coronary angiography at rest and after incremental doses of methylergometrine (intracoronary 2, 10, 30 microg) before and 20 min after either intracoronary estradiol 17beta (20 ng/mL at 1 mL/min for 20 min; 8 patients) or placebo (Dextrose 5%, 1 mL/min; 8 patients). RESULTS AND CONCLUSIONS: No significant differences were observed in baseline coronary artery diameter or area between the 2 groups. No significant differences in the degree of coronary artery constriction were observed after either estradiol 17beta or placebo at submaximal doses of methylergometrine. However, the degree of coronary artery constriction after maximal doses of methylergometrine was significantly attenuated by estradiol 17beta compared to placebo (change in diameter: -0.9+/-4.5% vs. -19+/-6%, p<0.001; change in area: -3.2+/-9% vs. -32.2+/-10%, p<0.001). Estradiol 17beta reduces coronary artery constriction following methylergometrine administration in menopausal patients with coronary artery disease. This effect may be related to the calcium-antagonist properties of the ovarian hormone.

Density of Chlamydia pneumoniae is increased in fibrotic and calcified areas of degenerative aortic stenosis.

BACKGROUND: The process of aortic degeneration associated with calcified aortic stenosis shares many similarities with coronary artery atherosclerosis. Inflammation and infection are involved in both diseases. Chlamydia pneumoniae has been identified in atherosclerotic plaques. However, the studies about the presence of C. pneumoniae in degenerative aortic stenotic valves are not conclusive. OBJECTIVE: We investigated whether an association exists between the density of C. pneumoniae and fibrosis or calcification in aortic stenosis. DESIGN: Autopsy and surgical specimens were divided into 3 groups: Normal, 11 normal autopsy valves Atherosclerosis, 10 autopsy valves from patients with systemic atherosclerosis and no aortic stenosis and Aortic stenosis, 14 surgical specimens of aortic valves replaced due to aortic stenosis. SETTING: Heart Institute (InCor), University of São Paulo Medical School. PATIENTS: Aortic valves from patients aged 52+/-16 years, 69+/-9 years, and 71+/-8 years. INTERVENTION: Specimens were evaluated by immunohistochemical technique (to detect C. pneumoniae antigens), in situ hybridization, and electron microscopy (to quantify the density of C. pneumoniae in the valves). MEASUREMENTS: The aortic stenosis group was analyzed according to 3 subregions: aortic stenosis-preserved, peripheral preserved regions; aortic stenosis-fibrosis, peri-calcified fibrotic tissue; and aortic stenosis-calcification, calcified nodules. RESULTS: The median values of C. pneumoniae antigens were 0.09, 0.30, 0.18, 1.33, and 3.3 in groups Normal, Atherosclerosis, Aortic stenosis-preserved, Aortic stenosis-fibrosis, and Aortic stenosis-calcification, respectively. The amount of C. pneumoniae was greater in the Atherosclerosis and Aortic stenosis-calcification groups than in the Normal group (P<0.05). C. pneumoniae was greater in the Aortic stenosis group in the calcified and fibrotic regions than in preserved region (P<0.05). CONCLUSION: An association was found between the higher density of C. pneumoniae and fibrosis/calcification in stenotic aortic valves.

[Predictive value of ventilatory and metabolic variables for risk of death in patients with cardiac failure]. / Valor preditivo de variáveis ventilatórias e metabólicas para óbito em pacientes com insuficiência cardíaca.

OBJECTIVE: To analyze the predictive value of respiratory, metabolic, and hemodynamic variables obtained during the cardiopulmonary stress test for the risk of death in patients with heart failure. METHODS: Eighty-seven NYHA Functional Class II and III patients were analyzed, ages 51 +/- 0.5 years, 26 of them with Chagas' disease, 30 with coronary ischemia, and 31 with idiopathic etiology. The cardiopulmonary stress test consisted of a ramp-protocol with 5 to 15 W/min workload increments performed on a bicycle-ergonometer until exhaustion. RESULTS: In this study, the multiple Cox regression analysis of age, height, weight, body surface, and gender showed that these parameters were not statistically significant control factors. Oxygen uptake, ventilatory equivalent of oxygen, ventilatory equivalent of carbon dioxide production, oxygen pulse, and end-tidal partial pressure of carbon dioxide at the anaerobic threshold, respiratory compensation point, and peak exercise proved to be important death predictors in heart failure patients. The relationship between the increase in carbon dioxide output as a function of the increase in minute ventilation, and the association between the oxygen uptake increase and the elevation of the workload from the beginning of exercise to the anaerobic threshold were statistically significant predictors of death in heart failure patients (p<0.05). CONCLUSION: The cardiopulmonary stress test makes it possible to evaluate ventilatory, metabolic, and hemodynamic variables that may be utilized as important markers of life prognosis in these patients.

[Exercise stress test: prognostic value for elderly patients with stable coronary atherosclerosis]. / Teste ergométrico: valor prognóstico em pacientes idosos com doença aterosclerótica coronariana estável.

OBJECTIVE: To study the prognostic value of exercise stress test variables in elderly patients with coronary atherosclerosis and exercise-induced ischemia. METHODS: Sixty-four elderly patients (61 men, 73 +/- 5 years old) with coronary atherosclerosis, verified by cardiac catheterization, that were clinically stable, had a left ventricle ejection fraction greater than or equal to 0.40 and developed myocardial ischemia during the exercise stress test were studied. The patients were evaluated every six months for cardiac events (death, myocardial infarction, unstable angina, angioplasty and myocardial revascularization). RESULTS: After a mean follow-up period of 48 months, 23 (36%) patients suffered cardiac events. There was no clinical or angiographical differences among the patients that suffered cardiac events and those that did not. Using multivariate analysis, the presence of chest pain during the exercise stress test (relative risk 2.668, p = 0.031) and the heart rate at the onset of ischemia (relative risk 0.966, p = 0.009) were associated with cardiac events. CONCLUSION: In this elderly population, the presence of chest pain during the exercise stress test and the heart rate at the onset of ischemia were associated with cardiac events. These variables could be useful for risk evaluation in patients with stable coronary atherosclerosis.

A time-series analysis of the relation between unemployment rate and hospital admission for acute myocardial infarction and stroke in Brazil over more than a decade.

BACKGROUND: The effect of socioeconomic stressors on the incidence of cardiovascular disease (CVD) is currently open to debate. Using time-series analysis, our study aimed to evaluate the relationship between unemployment rate and hospital admission for acute myocardial infarction (AMI) and stroke in Brazil over a recent 11-year span. METHODS AND RESULTS: Data on monthly hospital admissions for AMI and stroke from March 2002 to December 2013 were extracted from the Brazilian Public Health System Database. The monthly unemployment rate was obtained from the Brazilian Institute for Applied Economic Research, during the same period. The autoregressive integrated moving average (ARIMA) model was used to test the association of temporal series. Statistical significance was set at p<0.05. From March 2002 to December 2013, 778,263 admissions for AMI and 1,581,675 for stroke were recorded. During this time period, the unemployment rate decreased from 12.9% in 2002 to 4.3% in 2013, while admissions due to AMI and stroke increased. However, the adjusted ARIMA model showed a positive association between the unemployment rate and admissions for AMI but not for stroke (estimate coefficient=2.81±0.93; p=0.003 and estimate coefficient=2.40±4.34; p=0.58, respectively). CONCLUSIONS: From 2002 to 2013, hospital admissions for AMI and stroke increased, whereas the unemployment rate decreased. However, the adjusted ARIMA model showed a positive association between unemployment rate and admissions due to AMI but not for stroke. Further studies are warranted to validate our findings and to better explore the mechanisms by which socioeconomic stressors, such as unemployment, might impact on the incidence of CVD.

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.

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: 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.

Localized cerebral blood flow reductions in patients with heart failure: a study using 99mTc-HMPAO SPECT.

BACKGROUND AND PURPOSE: Reduced resting global cerebral blood flow has been previously detected in association with heart failure (HF), but it is not clear whether there are brain regions that could be specifically affected by those brain perfusion deficits. The authors used a fully automated, voxel-based image analysis method to investigate, across the entire cerebral volume, the presence of resting regional cerebral blood flow (rCBF) abnormalities in HF patients compared to healthy controls. METHODS: rCBF was evaluated with 99mTc-single-photon emission computed tomography in 17 HF patients (New York Heart Association functional class II or III) and 18 elderly healthy volunteers. Voxel-based analyses of rCBF data were conducted using the statistical parametric mapping software. RESULTS: Significant rCBF reductions in HF patients relative to controls (P<.05, corrected for multiple comparisons) were detected in 2 foci, encompassing, respectively, the left and right precuneus and cuneus and the right lateral temporoparietal cortex and posterior cingulated gyrus. In the HF group, there was also a significant direct correlation between the degree of cognitive impairment as assessed using the Cambridge Mental Disorders of the Elderly Examination and rCBF on a voxel cluster involving the right posterior cingulate cortex and precuneus, located closely to the site where between-group rCBF differences had been identified. CONCLUSIONS: These preliminary findings indicate that posterior cortical areas of the brain may be particularly vulnerable to brain perfusion reductions associated with HF and suggest that functional deficits in these regions might be relevant to the pathophysiology of the cognitive impairments presented by HF patients.

Value of C-reactive protein levels and IL-6 in predicting events levels in women at increased cardiovascular risk.

BACKGROUND: Elevated C-reactive protein (CRP) levels due to of heightened vascular inflammatory state in vascular conditions are often associated with elevated interleukin-6 (IL-6) levels since during inflammation CRP production in the liver is induced by IL-6. It has been suggested that CRP may be a predictors of unfavourable outcome in postmenopausal women (PMW) receiving hormone replacement therapy. Because of the possible metabolic effect of hormone replacement therapy (HRT) on CRP, the relative predictive importance of CRP and IL-6 levels in PMW receiving HRT remains to be elucidated. METHODS: We measured plasma levels of CRP and IL-6 levels in 346 consecutive PMW (mean age 66+/-9 years) with cardiovascular risk >20 in 10 years followed during a 36 month period. Women underwent measurement of inflammatory cytokines at baseline and were allocated to two groups according to the willingness to take hormone replacement therapy. All women underwent a further measurement of CRP and IL-6 at 3 and 6 months. Health status was assessed by out patient visits and hospital charts. RESULTS: During 1 year follow up, three patient died, four had a major cardiovascular event, three had a unstable angina, two had a transient ischemic attack and two patients underwent PTCA. PMW with events had higher CRP levels compared with patients with no events (1.9+/-0.61 versus 1.43+/-0.21, P<0.05) but still within the limits of normal. Also baseline IL-6 plasma levels were significantly higher in PMW with events than in those without events (0.87+/-0.23 versus 0.54+/-0.18, P <0.05). The increase in CRP and IL-6 with HRT was significantly higher in patients with events than in those with no events (CRP: 81+/-12 % versus 76+/-21%, P<0.05; IL-6 9+/-3 % versus -14+/-7%, P<0.05). In a stepwise multivariate analysis, IL-6 levels resulted a stronger predictor of outcome than CRP. CRP levels were predictors of future events only after removal of IL-6 levels and presence of cardiovascular symptoms from the analysis. CRP levels were associated with an unfavourable outcome only when IL-6 levels were also elevated. The increase in CRP with HRT during follow up was not associated to an increased event rate. CONCLUSION: Our study showed that CRP levels are increased in PMW receiving HRT. Elevated IL-6 levels may identify those PMW at increased 1 year risk. CRP levels predict events only when they are coupled with elevated IL-6 levels.