Buenaventura Brito Díaz

Sex hormones and autoimmunity.

Autoimmune diseases occur more in women than in men, and this may be attributable to the role of estrogens. Androgens promote autoimmune diseases with a profile of type 1 cytokines, such as rheumatoid arthritis, whereas estrogens promote autoimmune diseases with a type 2 cytokine profile, like systemic lupus erythematosus. Both androgens and estrogens regulate the Th1/Th2 balance. Type 1 autoimmune diseases are improved when decrease type 1 cytokines (i.e. during fasting), or when there is a rise in type 2 cytokines (increased estrogens, as in pregnancy). Type 2 autoimmune diseases improve when type 2 cytokines are diminished (decreased estrogen, as in post-partum period) or when type 1 response is stimulated.

Inverse Association Between Obesity and Antinuclear Antibodies in Women

To the Editor: More than 70% of all autoimmune illnesses occur in women, a figure that has been attributed to stimulation of the Th2 response by estrogens. However, a little-explored relationship is that which may exist between obesity and autoimmune disorders in women. Since the discovery of leptin1 it has been known that the cytokine-producing capacity of adipose tissue is high. Serum concentration of leptin is 3- to 4-fold higher in women than in men. However, little is known about the reasons for this difference. To date no studies have investigated the relationship between leptin and autoimmune disease in the…

Efficiency of different strategies to detect autoantibodies to extractable nuclear antigens.

Autoantibodies to extractable nuclear antigens (anti-ENA) are identified mainly in samples positive for antinuclear antibodies (ANA). Although the method of choice for ANA screening is indirect immunofluorescence (IIF), several techniques are available to detect anti-ENA. The aim of this study was to compare the efficiency of five different strategies to determine anti-ENA. During a 2-year period we screened ANA in 30375 samples with IIF, and the 4475 samples ANA positive were tested for anti-ENA by double immune diffusion screening or fluoroenzymeimmunoassay (Screening FI); anti-ENA specificities were then determined by line immunoassay (LIA) or fluoroenzymeimmunoassay (FI). We compared five strategies that involved FI or LIA identification of anti-ENA with or without prior screening, or an algorithm that combined fluorescence pattern, number of anti-ENA specificities requested by the clinician and ANA dilution titer. One cost unit (CU) was defined as the cost of 1 test of ANA determination. We detected 553 anti-ENA positive samples. The most efficient strategy was the algorithm, at a cost of 3.3 CU per sample processed, the second most efficient strategy was screening plus FI identification (cost=3.8 CU), and the third most efficient strategy was screening plus LIA identification (cost=3.9 CU). The fourth most efficient strategy was FI identification without prior screening (13.3 CU per sample) and the least efficient was LIA identification without prior screening (13.6 CU per sample). In conclusion, an algorithm that combined techniques for detection, ANA titer, fluorescence pattern and number of specificities requested was the most efficient strategy for determining anti-ENA.

Factores asociados al conocimiento y el control de la hipertensión arterial en Canarias

INTRODUCTION AND OBJECTIVES To analyze the factors associated with knowledge and control of hypertension in the adult population of the Canary Islands (18-75 years). METHODS We recruited a random sample of the general population aged ≥18 years. Hypertension was defined as systolic/diastolic blood pressure ≥140/90 mmHg or known hypertension (self-declared, or controlled hypertension <140/90 mmHg). The bivariate association of known and controlled hypertension with age, sex, anthropometry, serum lipids, medication, and lifestyle was corroborated by adjusting a multivariate logistic model. RESULTS We included 6675 participants. The prevalence of hypertension was higher in men (40% vs 31%, P<.001), who also had a lower frequency of treated and controlled hypertension. Female sex (P<.001), age ≥55 years (P<.001), obesity (P<.001), and diabetes (P<.001) were associated with known hypertension. The modifiable factors that, in spite of treatment, increased the risk of poor control of hypertension were alcohol consumption (>30 g/day, odds ratio [OR]=2.4, P<.001; >15-≤30 g/day, OR=2, P=.009; >5-≤15, g/day, OR=1.83, P=.004), obesity (body mass index ≥30, OR=2, P=.003; >24.9-<30, OR=1.7, P=.024), serum cholesterol >250 mg/dL (OR=1.6, P=.006) and elevated heart rate (>80 bpm, OR=1.45, P=.045; >70-≤80 bpm, OR=1.36, P=.038). CONCLUSIONS The awareness of hypertension increases with frequent use of the health system and with factors associated with known hypertension: female sex, age, underlying health problems. The modifiable factors associated with poor control of known hypertension are alcohol consumption, obesity, elevated heart rate, and hypercholesterolemia.

Factors associated with parietal cell autoantibodies in the general population

The presence in serum of parietal cell autoantibodies (PCA) is a characteristic of autoimmune gastritis. We determined the prevalence of PCA in the general population and investigate their association with type 2 diabetes, insulin resistance and lifestyle factors related with autoimmune gastritis. A cross-sectional study was performed, involving 429 individuals enrolled in a cohort study of the general population of the Canary Islands. All participants underwent physical examination, provided a blood sample and responded to a questionnaire regarding health and lifestyle factors. Serum concentrations of PCA, soluble CD40 ligand (sCD40L), C-peptide and glucose (to determine insulin resistance) were measured. The association of PCA with the other factors was determined with bivariate analysis, and logistic regression models were used to adjust the associations for age and sex. The prevalence of PCA was 7.8% (95% CI=10.3-5.3). The factors associated with PCA were female sex (p=0.032), insulin resistance (p=0.016), menopause (p=0.029) and sCD40L (p=0.019). Alcohol consumption (p=0.006) and smoking (p=0.005) were associated with low prevalences of PCA. After adjustment for age and sex, the association with PCA was confirmed for smoking (OR=0.1 [0.0-0.9]), alcohol consumption (OR=0.3 [0.1-0.9]), insulin resistance (OR=2.4 [1.1-4.9]), female sex (OR=2.4 [1.1-5.3]), sCD40L (OR=3.7 [1.2-11.4]) and menopause (OR=5.3 [1.2-23.3]). In conclusion, smoking and alcohol consumption acted as protective factors against the appearance of PCA in the general population, whereas female sex, menopause, insulin resistance and elevated serum sCD40L were risk markers for PCA. In patients who smoke or drink alcohol, clinicians should be cautious when using PCA to rule out autoimmune gastritis.

Autoantibody detection with indirect immunofluorescence on HEp-2 cells: Starting serum dilutions for systemic rheumatic diseases

Antinuclear antibodies (ANA) are determined, among other reasons, to identify samples which need a second test to detect the associated specificities. Our aim was to evaluate the clinical and economic impact generated by using an initial dilution for ANA of 1:160. We analyzed all samples for which ANA, anti-ENA and anti-dsDNA were requested over a 1-year period. ANA were detected by indirect immunofluorescence. Anti-ENA were analyzed with a combination of techniques. Anti-dsDNA were detected by radioimmunoassay. Cost analysis was performed by calculating the difference between two cut-offs (ANA 1:40 and 1:160). A total of 13,233 samples were processed for ANA, of which 59.9% were positive with the 1:40 cut-off and 39.2% with the 1:160 cut-off. At ANA titer 1:40, 0.2% of the samples were anti-ENA-positive and 2.2% were anti-dsDNA positive. Only ANA dilutions of 1:160 and higher showed significantly increased positive predictive value for anti-ENA (1.5 versus 0.2, p=0.029) and anti-dsDNA (8.3 versus 2.2, p<0.001) compared to the 1:40 titer. With the 1:160 cut-off, 16.6% fewer ANA tests, 41.8% fewer anti-ENA determinations and 36.4% fewer anti-dsDNA tests would have been needed. The average saving was 0.87 cost-units per sample (1 unit=2.06euro). We conclude that setting the starting dilution for ANA at 1:160 avoids unnecessary studies, increases the positive predictive values of ANA for anti-ENA and anti-dsDNA, and generates clinical and economic benefits.

Leptin, estrogens and cancer.

Obesity is a state of leptin resistance in which the membrane leptin receptor and the JAK-STAT pathway are blocked. This leads to increased intracellular concentrations of lipid metabolites, increased non-oxidative metabolism by adipocytes, and stimulation of the cell estrogen cycle. These factors are potentially oncogenic via the shared mitogen-activated protein kinase (MAPK), mitogen/extracellular signal-regulated kinase (MEK) and extracellular signal-regulated kinase (ERK) cellular pathways.

Acute Coronary Syndrome in the Young: Clinical Characteristics, Risk Factors and Prognosis

Background: To describe the characteristics of patients ≤40 years of age hospitalized for acute coronary syndrome, analyze the risk factors and identify the variables associated with prognosis. Methods: Case series of patients admitted between 2003 and 2012 inclusive in a tertiary hospital (123 consecutive cases admitted between 2003 and 2012), and case-control study (369 controls selected from the general population matched for sex and age with cases, at a ratio of 3:1). Outcome variables: Mortality, likelihood of survival without readmission for heart-related problems, extent of coronary disease as determined by coronary angiography and cardiovascular risk factors. Results: Mean age was 35.4±4.8 years and 83.7% of the participants were men. Myocardial infarction with abnormal Q wave (48%) and single-vessel involvement (44.7%) predominated. Intrahospital mortality was 1.6%. For the 108 patients eventually included in the follow-up, likelihood of readmission-free survival after 60 months was 69.3±4.8%. In the case group 36% of the patients admitted to using cocaine. Compared to controls, the prevalence in patients was higher for smoking (74.8 vs 33.1%, p<0001), diabetes (14.6% vs 5.1%, p=0.001), low HDL-cholesterol (82.9 vs 34.1%, p<0.001) and obesity (30.0 vs 20.3%, p=0.029). Decreased left ventricular ejection fraction (odds ratio=2.2, p=0.033) and smoking (odds ratio=7.8, p=0.045) were associated with readmission for coronary syndrome. Conclusion: Acute coronary syndrome in people younger than 40 years is associated with diabetes and unhealthy lifestyle: smoking, sedentary behavior (low HDL-cholesterol), cocaine use and obesity. The readmission rate is high, and readmission is associated with smoking and decreased ejection fraction.

Frecuencia cardiaca en reposo y enfermedad cardiovascular

Heart rate reflects autonomic nervous system activity. Numerous studies have demonstrated that an increased heart rate at rest is associated with cardiovascular morbidity and mortality as an independent risk factor. It has been shown a link between cardiac autonomic balance and inflammation. Thus, an elevated heart rate produces a micro-inflammatory response and is involved in the pathogenesis of endothelial dysfunction. In turn, decrease in heart rate produces benefits in congestive heart failure, myocardial infarction, atrial fibrillation, obesity, hyperinsulinemia, insulin resistance, and atherosclerosis. Alteration of other heart rate-related parameters, such as their variability and recovery after exercise, is associated with risk of cardiovascular events. Drugs reducing the heart rate (beta-blockers, calcium antagonists and inhibitors of If channels) have the potential to reduce cardiovascular events. Although not recommended in healthy subjects, interventions for reducing heart rate constitute a reasonable therapeutic goal in certain pathologies.

Incidence, Mortality and Positive Predictive Value of Type 1 Cardiorenal Syndrome in Acute Coronary Syndrome.

Objectives To determine whether the risk of cardiovascular mortality associated with cardiorenal syndrome subtype 1 (CRS1) in patients who were hospitalized for acute coronary syndrome (ACS) was greater than the expected risk based on the sum of its components, to estimate the predictive value of CRS1, and to determine whether the severity of CRS1 worsens the prognosis. Methods Follow-up study of 1912 incident cases of ACS for 1 year after discharge. Cox regression models were estimated with time to event (in-hospital death, and readmission or death during the first year after discharge) as the dependent variable. Results The incidence of CRS1 was 9.2/1000 person-days of hospitalization (95% CI = 8.1–10.5), but these patients accounted for 56.6% (95% CI = 47.4–65.) of all mortality. The positive predictive value of CRS1 was 29.6% (95% CI = 23.9–36.0) for in-hospital death, and 51.4% (95% CI = 44.8–58.0) for readmission or death after discharge. The risk of in-hospital death from CRS1 (RR = 18.3; 95% CI = 6.3–53.2) was greater than the sum of risks associated with either acute heart failure (RR = 7.6; 95% CI = 1.8–31.8) or acute kidney injury (RR = 2.8; 95% CI = 0.9–8.8). The risk of events associated with CRS1 also increased with syndrome severity, reaching a RR of 10.6 (95% CI = 6.2–18.1) for in-hospital death at the highest severity level. Conclusions The effect of CRS1 on in-hospital mortality is greater than the sum of the effects associated with each of its components, and it increases with the severity of the syndrome. CRS1 accounted for more than half of all mortality, and its positive predictive value approached 30% in-hospital and 50% after discharge.