Cristina Karohl

Sex differences in mental stress-induced myocardial ischemia in young survivors of an acute myocardial infarction.

Objectives Emotional stress may disproportionally affect young women with ischemic heart disease. We sought to examine whether mental stress–induced myocardial ischemia (MSIMI), but not exercise-induced ischemia, is more common in young women with previous myocardial infarction (MI) than in men. Methods We studied 98 post-MI patients (49 women and 49 men) aged 38 to 60 years. Women and men were matched for age, MI type, and months since MI. Patients underwent technetium-99m sestamibi perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores were obtained with observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify ischemia under both stress conditions. Results Women 50 years or younger, but not older women, showed a more adverse psychosocial profile than did age-matched men but did not differ for conventional risk factors and tended to have less angiographic coronary artery disease. Compared with age-matched men, women 50 years or younger exhibited a higher SDS with mental stress (3.1 versus 1.5, p = .029) and had twice the rate of MSIMI (SDS ≥3; 52% versus 25%), whereas ischemia with physical stress did not differ (36% versus 25%). In older patients, there were no sex differences in MSIMI. The higher prevalence of MSIMI in young women persisted when adjusting for sociodemographic and life-style factors, coronary artery disease severity, and depression. Conclusions MSIMI post-MI is more common in women 50 years or younger compared with age-matched men. These sex differences are not observed in post-MI patients who are older than 50 years.

Noninvasive imaging for assessment of calcification in chronic kidney disease

Vascular calcification is highly prevalent in patients with chronic kidney disease and has a progressive course. Several cardiovascular and uremia-related risk factors, such as abnormalities in mineral metabolism, contribute to the development of vascular calcification, although the pathophysiological mechanisms are still unclear. The presence and extent of vascular calcification is associated with an increased risk of cardiovascular events and mortality. By contrast, patients who do not have calcification seem to have a good prognosis, with minimal or no calcification progression over an extended period of time. A number of noninvasive imaging methods are available to detect vascular calcification and may help clinicians to make therapeutic decisions. Cardiac CT remains the reference standard to detect and quantify coronary artery, aortic and cardiac valve calcification. However, the high cost of equipment, the inability to perform in-office testing and the expertise required limit its use on a routine basis. Other imaging methods, such as planar X-ray, ultrasound and echocardiography, are appropriate alternatives to evaluate vascular and valvular calcification. In this Review, we discuss the noninvasive imaging methods most frequently used to assess vascular and valvular calcification, with their advantages and limitations.

Heritability of Renal Function and Inflammatory Markers in Adult Male Twins

Background: Loss of renal function is accompanied by a progressive increase in markers of inflammation; it is unknown whether they share common genetic pathways. Study Design: We evaluated the shared heritability of estimated glomerular filtration rate (eGFR) and markers of inflammation and endothelial activation in 524 twin males from the Vietnam Era Twin Registry; 9 twins were excluded due to incomplete or incorrect data. Models were adjusted for age, race, body mass index, smoking, hypertension, diabetes mellitus, prior coronary artery disease and intercurrent medications. Results: The mean eGFR was 89 ± 13 ml/min/1.73 m2 (range 35–146); eGFR, intracellular adhesion molecule (ICAM) and TNF-α receptor (TNF-αR) were moderately heritable (all ∼50%), while IL-6 receptor (IL-6R) and P-selectin were highly heritable (68 and 76%, respectively). IL-6R and TNF-αR showed a significant inverse association with eGFR (p = 0.04 and p < 0.0001) while the association with ICAM and P-selectin was direct (p = 0.001 and p = 0.06). Bivariate structural equation models showed that the association between eGFR and biomarkers was due to unique environmental factors and there were no shared genetic pathways. Conclusion: We found no shared genetic pathways between renal function and inflammation. Thus, increased inflammation represents a response to declining renal function rather than being a mechanism contributing to renal deterioration.

Coronary calcification and its association with mortality in haemodialysis patients.

Aim:  Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.

Vitamin D Status and Coronary Flow Reserve Measured by Positron Emission Tomography: A Co-Twin Control Study

CONTEXT Vitamin D insufficiency is associated with increased cardiovascular events in the general population. Additionally, low serum 25-hydroxyvitamin D [25(OH)D] is associated with endothelial dysfunction and arterial stiffness. However, little is known about the association between serum 25(OH)D level and myocardial blood flow. OBJECTIVE Our objective was to examine the association between serum 25(OH)D levels and coronary flow reserve (CFR) measured by (13)N-positron emission tomography in asymptomatic middle-aged male twins. DESIGN The Emory Twin Study is a cross-sectional study of soldiers from the Vietnam Era Registry. SETTING The study was conducted at the General Clinical Research Center, Emory University, Atlanta, GA. PARTICIPANTS A total of 368 middle-aged male twins were enrolled for the study. Serum 25(OH)D levels were measured in all subjects and classified as vitamin D insufficiency [25(OH)D <30 ng/ml] or sufficiency [25(OH)D ≥30 ng/ml]. Positron emission tomography with [(13)N]ammonia was used to evaluate myocardial blood flow at rest and after adenosine stress. CFR was measured as the ratio of maximum to rest myocardial blood flow. MAIN OUTCOME MEASURE Primary outcome was CFR measurement. RESULTS Mean overall serum 25(OH)D concentration was 37.0 ± 21.4 ng/ml; 167 twins (45%) were vitamin D insufficient. CFR was significantly lower in subjects with vitamin D insufficiency compared with subjects with vitamin D sufficiency (2.41 vs. 2.64; P = 0.007), even after adjustment for traditional cardiovascular risk factors, serum PTH, calcium, and phosphorus levels, and season. An abnormal CFR (CFR <2) was more prevalent in subjects with vitamin D insufficiency than with vitamin D sufficiency (31 vs. 20%; P = 0.03). In addition, in vitamin D status-discordant twin pairs, CFR was significantly lower in the vitamin D-insufficient twin than in the vitamin D-sufficient co-twin (2.35 vs. 2.58; P = 0.037). CONCLUSION Vitamin D insufficiency is associated with lower CFR in men. This association may help explain some of the increased cardiovascular risk reported in individuals with vitamin D insufficiency.

Situação do hiperparatireoidismo secundário autônomo no Brasil: dados do Censo Brasileiro de Paratireoidectomia

INTRODUCTION Secondary hyperparathyroidism (SHP) is a common and serious complication of chronic kidney disease (CKD), with a negative impact on morbidity and mortality. Despite advances in the clinical management of SHP, treatment failure still occurs in a significant number of patients. In such cases, parathyroidectomy (PTx) is indicated. OBJECTIVE To have an overview of the prevalence of severe SHP and of its surgical treatment in hemodialysis (HD) patients in Brazil. METHODS This was an observational and descriptive study. Data were obtained from questionnaires posted to 660 dialysis units (DU). RESULTS Results are expressed in absolute values and percentages, or means and standard deviation, as appropriate. 226 (34%) DU answered the questionnaire, providing data about 32,264 HD patients. The prevalence rate of severe SHP (PTH > 1,000 pg/mL) was 10.7 % (n = 3,463). 68 hospitals countrywide perform PTX. Around 40% of them are university centers. 49 (21.7%) DU reported not to have a specialized medical center to refer their patients with severe SHP. 74 (33%) DU reported that the time interval between surgery indication and its performance was over 6 months. The main recognized obstacles to surgery performance were: difficulty to perform the preoperative exams, lack of head and neck surgeons and the long waiting time. CONCLUSIONS Although severe SHP is highly prevalent in Brazil, a significant number of patients do not have access to PTx. Better public health policies and liaison between nephrologists and head and neck surgeons are urgently required to change this reality.INTRODUCTION: Secondary hyperparathyroidism (SHP) is a common and serious complication of chronic kidney disease (CKD), with a negative impact on morbidity and mortality. Despite advances in the clinical management of SHP, treatment failure still occurs in a significant number of patients. In such cases, parathyroidectomy (PTx) is indicated. OBJECTIVE: To have an overview of the prevalence of severe SHP and of its surgical treatment in hemodialysis (HD) patients in Brazil. METHODS: This was an observational and descriptive study. Data were obtained from questionnaires posted to 660 dialysis units (DU). RESULTS: Results are expressed in absolute values and percentages, or means and standard deviation, as appropriate. 226 (34%) DU answered the questionnaire, providing data about 32,264 HD patients. The prevalence rate of severe SHP (PTH > 1,000 pg/mL) was 10.7 % (n = 3,463). 68 hospitals countrywide perform PTX. Around 40% of them are university centers. 49 (21.7%) DU reported not to have a specialized medical center to refer their patients with severe SHP. 74 (33%) DU reported that the time interval between surgery indication and its performance was over 6 months. The main recognized obstacles to surgery performance were: difficulty to perform the preoperative exams, lack of head and neck surgeons and the long waiting time. CONCLUSIONS: Although severe SHP is highly prevalent in Brazil, a significant number of patients do not have access to PTx. Better public health policies and liaison between nephrologists and head and neck surgeons are urgently required to change this reality.

Approach to Cardiovascular Disease Prevention in Patients With Chronic Kidney Disease

Opinion statementChronic kidney disease (CKD) is associated with a large burden of cardiovascular risk factors ultimately leading to increased cardiovascular events and mortality. Prevention of cardiovascular disease (CVD) in CKD involves early identification of individuals at high-risk of renal disease. In fact, substantial evidence points to a complex bidirectional relationship between CKD and CVD. Therefore, most interventions directed at CKD prevention should include multiple risk factor interventions with the goal of preventing CVD events while slowing progression of CKD. Clearly, prevention of CVD in CKD is a complex task and requires a multidisciplinary team approach, with a well-defined program, rational targets for each risk factor, and implementation of the most effective intervention strategies. Although several interventions to prevent CVD have proven effective in the general population and in individuals at high risk for CVD, a true benefit in patients with CKD remains to be demonstrated for several of them. A few rational targets of intervention should be optimal blood pressure control, reduction of proteinuria, treatment of dyslipidemia, good control of diabetes, smoking cessation, dietary salt restriction, achievement of normal body mass index, partial correction of anemia, and management of mineral metabolism abnormalities. Lifestyle modification and pharmacological therapy with renin-angiotensin blockers, β-blockers, diuretics, statins, and aspirin should be encouraged in the early stages of CKD.

The pitfall of treating low bone turnover: Effects on cortical porosity

Although it is recognized that cortical bone contributes significantly to the mechanical strength of the skeleton, little is known about this compartment from bone biopsy studies, particularly in CKD patients. In addition, there is no prospective data on the effects of CKD-MBD therapy on cortical porosity (Ct.Po). This is a post hoc analysis on data from a randomized controlled trial on the effects of different phosphate binders on bone remodelling. Therapy was adjusted according to the first biopsy, and included sevelamer or calcium acetate, calcitriol and changes in calcium dialysate concentration. We measured Ct.Po at baseline and one year after. Fifty-two patients (46±13years old, 67% women and 60% white) were enrolled. Ct.Po was already high at baseline in 85% of patients [30% (17, 46)] and correlated with PTH (p=0.001). Low bone turnover was seen in 28 patients (54.9%). After one-year treatment, PTH increased in patients with low turnover, as intended. However, increased Ct.Po was seen in 49 patients (94%). This increase correlated with the delta of phosphate (p=0.015) and the delta of PTH (p=0.03); it was also higher among non-white patients than in white patients (p=0.039). The risk of increase in Ct.Po was 4.5 higher among non-white patients. Adjusted multiple regression analysis showed that the delta of Ct.Po was dependent on delta PTH and race (r(2)=0.193). We concluded that in an attempt to increase bone turnover, the increase in PTH levels might be associated with higher cortical porosity, particularly in non-white patients. Whether this finding leads to a high risk of fracture deserves further investigation.

Protocolo clínico e diretrizes terapêuticas para o tratamento do hiperparatireoidismo secundário em pacientes com doença renal crônica

INTRODUCAO A doenca renal cronica (DRC) afeta 5-10% da populacao mundial e sua incidencia no Brasil tem aumentado, devido ao numero crescente de pacientes diagnosticados, principalmente os portadores de diabetes mellitus, hipertensao arterial, bem como pelo aumento da longevidade da populacao. […] Protocolo clinico e diretrizes terapeuticas para o tratamento do hiperparatireoidismo secundario em pacientes com doenca renal cronica1 Serviço de Nefrologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil. 2 Serviço de Nefrologia da Universidade Federal de São Paulo, São Paulo, Brasil. 3 Escola de Medicina, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brasil. 4 Departamento de Medicina Interna da Universidade Federal da Bahia, Brasil. 5 Serviço de Nefrologia da Universidade Federal do Rio Grande do Sul, Brasil. 6 Serviço de Nefrologia da Universidade Federal Fluminense, Niterói, RJ, Brasil. 7 Serviço de Nefrologia da Universidade Federal de Pernambuco, Brasil.

Guidelines on Bone Mineral Disorder in Chronic Kidney Disease - Addendum Chapter 2

1 – AVALIACAO DOS NIVEIS DE PARATORMONIO (PTH) E FOSFATASE ALCALINA (FA) NA DRC 1.1 – Os niveis sericos de PTH devem ser analisados em todos os pacientes com DRC, cuja taxa de filtracao glomerular (TFG) for inferior a 60 mL/min/1,73 m2 (Evidencia). Deve-se modificar a frequencia de avaliacao dos niveis sericos de PTH se os resultados das analises mostrarem uma tendencia de elevacao ou de descenso ou apos a instituicao do tratamento, seja ele para reduzir ou elevar os [...]