Large Spanish Population Research Articles

The "UNAV-experience of living with chronic heart failure scale": a psychometric validation study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Plan Estatal de I+D+I 2013-2016 (2013-2016 State Plan for Scientific and Technical Research and Innovation) of the Spanish Government and co-financed by the Subdirectorate-General for the Evaluation and Promotion of Research of the Carlos III Health Institute (Instituto de Salud Carlos III - ISCIII) and the European Regional Development Fund (Fondos Europeos de Desarrollo Regional - FEDER) Introduction No validated patient-reported scale has been identified focused on exploring the life experience of people with chronic heart failure. Its development is necessary to address the person's view as a unitary being, and understand the illness as a health experience embedded in the person's life history. Purpose This study aimed to analyse the psychometric properties of the "UNAV-Experience of Living with Chronic Heart Failure Scale" in a large Spanish population. Methods A test-retest validation study was conducted between June 2020 and May 2022. The study was performed in five Spanish hospitals' outpatient heart failure units. The sample consisted of 300 adult patients with chronic heart failure with functional class II-IV. The test-retest was performed with 50 of these patients. Sociodemographic data, clinical data, the Minnesota Living With Heart Failure Questionnaire, the Kansas City Cardiomyopathy Questionnaire and the UNAV-Experience of Living with Chronic Heart Failure Scale were collected. The adjustment of the data to the Rasch model was analysed, as well as psychometric analyses according to classical test theory: data quality and acceptability, reliability and construct validity. Results The initial version of 53 items (developed based on the results of a qualitative study, a systematic literature review, the opinion of a panel of experts and a pilot study) was finally reduced to 30 items. Through Rasch's analysis, five dimensions were identified that made up this scale: 1) Living with CHF involves profound personal changes (7 items); 2) People living with CHF have to accept their situation (5 items); 3) People with CHF need to feel that their life is normal (7 items); 4) People with CHF need to live with hope (5 items); 5) People with CHF feel that their situation negatively influences their close environment (6 items). No subscales showed asymmetry or floor effect. All items had a corrected total item correlation >0.30. The homogeneity index of the items ranged from 0.31 to 0.57, and Cronbach's alpha ranged from 0.73 to 0.87. The intraclass correlation coefficient was between 0.79 and 0.89. All subscales showed significant differences by gender (p<0.001), except for the Acceptance subscale. The subscales on Profound Change, Acceptance and Hope showed significant differences by educational level (p<0.05). Regarding functional class, subscale scores significantly differed between class II and III-IV (p<0.01). Conclusions The UNAV-Experience of Living with Chronic Heart Failure Scale is an original and valid tool to measure the experience of living with chronic heart failure from the person's perspective.

Genome-wide significant risk factors on chromosome 19 and the APOE locus.

The apolipoprotein E (APOE) gene on chromosome 19q13.32, was the first, and remains the strongest, genetic risk factor for Alzheimer’s disease (AD). Additional signals associated with AD have been located in chromosome 19, including ABCA7 (19p13.3) and CD33 (19q13.41). The ABCA7 gene has been replicated in most populations. However, the contribution to AD of other signals close to APOE gene remains controversial. Possible explanations for inconsistency between reports include long range linkage disequilibrium (LRLD). We analysed the contribution of ABCA7 and CD33 loci to AD risk and explore LRLD patterns across APOE region. To evaluate AD risk conferred by ABCA7 rs4147929:G>A and CD33 rs3865444:C>A, we used a large Spanish population (1796 AD cases, 2642 controls). The ABCA7 rs4147929:G>A SNP effect was nominally replicated in the Spanish cohort and reached genome-wide significance after meta-analysis (odds ratio (OR)=1.15, 95% confidence interval (95% CI)=1.12–1.19; P = 1.60 x 10-19). CD33 rs3865444:C>A was not associated with AD in the dataset. The meta-analysis was also negative (OR=0.98, 95% CI=0.93–1.04; P=0.48). After exploring LRLD patterns between APOE and CD33 in several datasets, we found significant LD (D’ >0.20; P <0.030) between APOE-Ɛ2 and CD33 rs3865444C>A in two of five datasets, suggesting the presence of a non-universal long range interaction between these loci affecting to some populations. In conclusion, we provide here evidence of genetic association of the ABCA7 locus in the Spanish population and also propose a plausible explanation for the controversy on the contribution of CD33 to AD susceptibility.

Molecular characterization of congenital myasthenic syndromes in Spain

Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic disorders, all of which impair neuromuscular transmission. Epidemiological data and frequencies of gene mutations are scarce in the literature. Here we describe the molecular genetic and clinical findings of sixty-four genetically confirmed CMS patients from Spain. Thirty-six mutations in the CHRNE, RAPSN, COLQ, GFPT1, DOK7, CHRNG, GMPPB, CHAT, CHRNA1, and CHRNB1 genes were identified in our patients, with five of them not reported so far. These data provide an overview on the relative frequencies of the different CMS subtypes in a large Spanish population. CHRNE mutations are the most common cause of CMS in Spain, accounting for 27% of the total. The second most common are RAPSN mutations. We found a higher rate of GFPT1 mutations in comparison with other populations. Remarkably, several founder mutations made a large contribution to CMS in Spain: RAPSN c.264C > A (p.Asn88Lys), CHRNE c.130insG (Glu44Glyfs*3), CHRNE c.1353insG (p.Asn542Gluf*4), DOK7 c.1124_1127dup (p.Ala378Serfs*30), and particularly frequent in Spain in comparison with other populations, COLQ c.1289A > C (p.Tyr430Ser). Furthermore, we describe phenotypes and distinguishing clinical signs associated with the various CMS genes which might help to identify specific CMS subtypes to guide diagnosis and management.

A cross‐sectional study of the association between circulating TSH level and lipid profile in a large Spanish population

Some evidence suggests that high serum TSH levels are associated with an adverse lipid profile, but this association is not clear when plasma TSH is within the reference range. Nevertheless, these studies have never been conducted in Spain, a country with a strong adherence to the Mediterranean diet. The study aim was to analyse the association between blood TSH levels and circulating lipids in a large Spanish population and set up a TSH reference range in different age, gender and Body Mass Index (BMI) subpopulations from our cohort. Cross-sectional study on 20 783 subjects. We analysed circulating levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and triglycerides (TG) and compared them with TSH serum levels. Discriminant function analysis was used to determine the TSH cut-off level from where hyperlipidaemia developed. In individuals free of thyroid dysfunction, the mean and the 95% TSH (mU/l) reference limits were 2·20 and 0·72-4·43, respectively. We observed a sex-related difference in TSH concentration (men, 2·07 and 0·72-4·29; women, 2·29 and 0·72-4·49; P < 0·01). We also observed a weight-related difference in TSH concentration (BMI < 30 kg/m(2) , 2·16 and 0·72-4·39; BMI ≥ 30 kg/m(2) , 2·28 and 0·71-4·47; P < 0·01). TSH was positively associated with TC, TG and LDLc levels and negatively with HDLc. We found an association between TSH and lipids in that as TSH increased, the lipid profile became less favourable, even within the normal range. Additionally, TSH reference ranges varied according to gender, age and BMI.

Prevalence of abnormal urinary albumin excretion in a population‐based study in Spain: results from the HERMEX Study

HERMEX is a population-based study which try to evaluate the relative weight of cardiovascular risk factors in the population of Extremadura. This report provides the data obtained about microalbuminuria in a large Spanish population. Observational, cross-sectional, population-based study. A total of 3402 subjects were randomly selected from the Health Care System of Extremadura. The final sample included 2813 subjects (mean age 51·2 years, 53·5% female). Urinary albumin excretion rate (UAER) in first morning urine sample was analysed. Microalbuminuria was diagnosed when UAER was ≥ 22 in men or ≥ 31 mg/g in women. Prevalence of abnormal UAER in general population was 5·5% (microalbuminuria: 4·7%; proteinuria 0·8%). Microalbuminuria grew slightly in patients between 65 and 74 years and showed a dramatic increase in subject older than 75 years (P < 0·001). Men showed a high prevalence of microalbuminuria (5·8% vs. women 3·6%; P = 0·006 chi-squared test). Increased UAER was more common in obese subjects (6·7% vs. 2·3%, P < 0·001), hypertensive patients (8·3% vs. 2·3%, P < 0·001) and diabetic ones (10·9% vs. 3·7%, P < 0·001). The multivariate analysis showed a positive correlation of abnormal UAER with body mass index (BMI), systolic blood pressure, plasma creatinine and triglyceride levels. A low frequency of abnormal UAER was detected in a randomly selected sample of Spanish general population. This finding agreed with the low rates of cardiovascular mortality and morbidity observed in Spain in spite of a high prevalence of classic cardiovascular risk factors.

PCV120 Quality of Life in Chronic Symptomatic Heart Failure Patients in Spain, insight from the Inoescaro Study

To analyze, for the first time in a large Spanish population of heart failure pts, quality of life according to NYHA class II, III or IV using generic and specific quality of life questionnaires. A descriptive analysis of a multicenter, prospective observational study was performed. Pts who met inclusion criteria were followed-up for a period of 12 months, with 3 visits programmed at baseline, 6 months and 12 months. A total of 9 Spanish hospitals were involved in the study. Questionnaires used to measure quality of life were: EQ-5D (generic questionnaire), Minessotta living with heart failure- MLWHF (specific questionnaire) and Barthel Index (index of independence). A total of 330 pts completed the study, 74.2% men, mean age was 62.9 years. 82.4% were in NYHA class II, 16.4% NYHA class III and 1.2% NYHA class IV. A total of 20 pts died along the period of study and 25 pts did not complete follow up. Significant differences were observed in Barthel Index's scores depending on class: class II 97.2 ± 7.3 vs. Class III-IV 91.4 ± 14.3. Related to EQ-5D scores, individuals in class II had a mean value of 0.8058 ± 0.2048 (out of 1), and mean VAS value of 56.75 ± 17.39 (out of 100). Individuals in NYHA class III-IV had a mean value of 0.6135 ± 0.3032 (out of 1) and mean VAS value of 50.45 ± 20.24 (out of 100). In a MLWHF questionnaire analyses, pts in NYHA class II showed a mean score of 29.81 ± 18.57 while pts in NYHA class III-IV showed a mean score of 48.53 ± 17.97. Chronic heart failure patients in NYHA III and IV seemed to have a higher grade for physical disability and worse health-related quality of life compared to patients in NYHA II and population of similar age.

A putative “hepitype” in the ATM gene associated with chronic lymphocytic leukemia risk

Chronic lymphocytic leukemia (CLL) cells are characterized by several chromosomal lesions. Some of these aberrations imply chromosome breaks as a result of unrepaired double strand breaks (DSBs) in the DNA. The ATM (ataxia telangiectasia-mutated) protein is the principal integrator of cellular responses to DSBs. ATM deletion is also an adverse prognostic factor in CLL. Taking this into account, we evaluated if genetic and/or epigenetic variation in the ATM gene may modulate the individual susceptibility to develop CLL. Our case-control association study was performed in a large Spanish population of 1,503 individuals, including 742 patients with CLL and 761 controls. We identified one haplotype within the ATM gene that confers an increased risk of CLL development (OR = 1.33; 95% CI: 1.10-1.60). Two polymorphisms of this ATM haplotype eliminated one CpG site each in Introns 15 and 61, causing changes in DNA methylation pattern. These data provide the first evidence for the existence of a putative "hepitype" in the ATM gene associated with CLL risk.

Calibrating the SCORE Cardiovascular Risk Chart for Use in Spain

The Third Joint European Task Force on cardiovascular prevention recommended the SCORE function for predicting 10-year cardiovascular mortality should be used to guide decision-making on clinical interventions. The objective of the present study was to calibrate the function for use in Spain. A model was developed to apply the hazard ratios for cardiovascular mortality at 10 years in SCORE study cohorts to the mean age- and sex-specific risk factors found in the third survey of the MONICA-Catalonia study (1994-96) and to 10-year cardiovascular survival function for the Spanish population based on mortality rates for the year 2002. The estimated risks derived using the calibrated SCORE function were 13% higher than those estimated using the low-risk algorithm. However, the differences between the two varied with age, sex, and, in particular, smoking history. The calibrated SCORE risk chart identified 32 high-risk situations that were not registered in the original low-risk SCORE chart. However, 50% of these situations had a low or zero prevalence. The maximum percentage of subjects who were newly identified as being at a high risk using the calibrated chart was 22%. Most differences were observed in men aged over 55 years. While risk estimates based on sufficiently large Spanish population cohorts are still not available, application of the original cardiovascular risk function calibrated for use in Spain should enable the appropriate clinical and public health decisions to be taken.

“His Majesty’s Most Loyal Vassals”: The Indian Nobility and Tuúpac Amaru

“His Majesty’s Most Loyal Vassals”: The Indian Nobility and Tuúpac Amaru

Normal Values for Photopic and Mesopic Letter Contrast Sensitivity

The exponential increase of patients having refractive surgery has increased the number of patients with night vision disturbances, such as decreased contrast sensitivity. However, there are no standard contrast sensitivity scales in normal persons in the mesopic range. We describe Pelli-Robson contrast sensitivity under photopic and mesopic luminance conditions in a large Spanish population over a wide range of age groups to provide normal values. A further aim was to evaluate the effect of photopic visual acuity on photopic and mesopic contrast sensitivity. A cross-sectional study was performed on 292 participants stratified by age into six groups. Binocular contrast sensitivity was determined with best spectacle correction using the Pelli-Robson letter chart at 1 m under photopic (85 cd/m2) and mesopic (0.15 cd/m2) luminance conditions. Phototopic letter contrast sensitivity began to decrease gradually from the 61 to 70-year-old age group onward, and for mesopic conditions, from the 51 to 60-year-old age group onward. The reduction in mean contrast sensitivity between the oldest and the youngest age groups was 0.20 log units (photopic) and 0.33 log units (mesopic). Loss in contrast sensitivity due to luminance (two successive triplets) increased slightly with age. Both photopic and mesopic letter contrast sensitivity significantly improved as photopic visual acuity increased. Under mesopic conditions, Pelli-Robson contrast sensitivity began to decline 1 decade earlier than under photopic conditions and was affected by visual acuity. Normal values for mesopic contrast sensitivity could be of help in deciding whether mesopic function is normal or a decrease in contrast sensitivity is pathologic in nature.

No evidence for association of the monocyte chemoattractant protein-1 (−2518) gene polymorphism and Alzheimer's disease

Activation of microglia is a central part of the chronic inflammatory process in Alzheimer disease (AD). The monocyte chemoattractant protein-1 (MCP-1) is a chemokine that plays a role in microglial migration and accumulation at sites of beta-amyloid deposition in senile plaques in the AD brain. A polymorphism in the regulatory region (−2518) of the MCP-1 gene affects the level of MCP-1 expression, and has been associated with a stronger inflammatory response and higher peripheral tissue damage in chronic inflammatory diseases. We investigated whether the MCP-1 (−2518) polymorphism might be responsible for susceptibility to AD in a large Spanish population, utilizing a clinically well-defined group of 328 sporadic AD patients and 315 control subjects. We also examined the combined gene effects between MCP-1 and other proinflammatory cytokine genes such as interleukin-1A (IL-1A) and tumor necrosis factor-α (TNF-α), and the apolipoprotein E (APOE) gene. In the present study, neither the MCP-1 (−2518) G allele itself nor its interaction with the IL-1A (−889) allele 2, TNF-α (−850) allele T or APOE ϵ4 allele conferred increased risk for AD.

Consumption of fruit and wine and the decline in cerebrovascular disease mortality in Spain (1975-1993).

This study examines the changes in provincial distribution of cerebrovascular disease (CVD) mortality and its socioeconomic and lifestyle risk factors to identify those factors that have most greatly contributed to the decline in CVD mortality in Spain during the period 1975-1993. We performed a study using data aggregated at a provincial level. Mortality data were taken from official vital statistics, while data on risk factors were obtained from surveys of representative large Spanish population samples. Correlation and multiple linear regression analyses were performed on percent changes in age-standardized CVD mortality from 1975-1979 to 1989-1993 and its potential determinants during the period 1964-1980. CVD mortality was higher in the southern and eastern (Mediterranean coast) provinces in 1975-1979 and again in 1989-1993. Between these periods there was a 55% decline in CVD mortality, which affected all provinces but was greater in those with a lower CVD mortality (r = -0.31, P = 0.03). The 1964-1980 period witnessed an increase in the intake of most foodstuffs and all types of fats. However, there was a decrease in the consumption of vegetables and legumes and in the proportion of illiteracy among the population older than 45 years. The greatest increase in fruit and fish consumption and the greatest decrease in illiteracy were registered by Spain's northernmost provinces, the same provinces that recorded the greatest decline in CVD mortality. Changes in fruit, wine, and fish intake accounted for 22% of the variation in the decline in CVD mortality. The increase in fruit consumption and decrease in wine consumption showed a statistically significant relationship (P < or = 0.04) with the decline in CVD mortality. The increase in fruit and decrease in wine consumption from 1964-1980 may have contributed to the decline in CVD mortality in Spain during 1975-1993.

Socioeconomic level, sedentary lifestyle, and wine consumption as possible explanations for geographic distribution of cerebrovascular disease mortality in Spain.

The geographic distribution of cerebrovascular disease (CVD) mortality in Spain spans a wide range, from provinces where mortality is low (70/100,000) and close to that of the United States and other Anglo-Saxon countries, to others where mortality is high (180/100,000) and more akin to that of Portugal and the Mediterranean and central European countries. This report seeks to identify the socioeconomic and lifestyle factors that most contribute to the geographic pattern of CVD mortality in Spain. We performed a study using data collected at a provincial level. Mortality data were taken from official vital statistics, and data on risk factors were obtained from surveys of representative large Spanish population samples. Correlation and multiple linear regression analyses were performed on standardized CVD mortality ratios and potential determinants of mortality for the period 1989 to 1993. CVD mortality, unemployment and illiteracy rates, blond cigarette smoking, and sedentary lifestyle proved substantially higher in the south and east (Mediterranean coast) of Spain. Saturated fatty acid intake and wine consumption were both lower in these regions, however. Illiteracy, wine consumption, sedentary lifestyle, high blood pressure, blond cigarette smoking, prevalence of diabetes, and body mass index > or = 30 explained 59% of the variation in CVD mortality. Only illiteracy, sedentary lifestyle, and wine consumption registered a statistically significant relationship (P < .05) with CVD mortality. Whereas lower consumption of wine showed a negative association with CVD mortality, higher consumption revealed a positive association. Socioeconomic level, as measured by illiteracy, sedentary lifestyle, and wine consumption, may partly explain the higher CVD mortality registered for regions situated in the south and east of Spain.