Current causes of death in familial hypercholesterolemia

Background Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by high low-density lipoprotein cholesterol (LDLc) and a high risk of premature cardiovascular disease (CVD). The molecular bases have been well defined, and effective lipid lowering is possible. This analysis aimed to study the current major causes of death of genetically defined heterozygous familial hypercholesterolemia (heFH). Methods A case‒control study was designed to analyse life-long mortality in a group of heFH and control families. Data from first-degree family members of cases and controls (nonconsanguineous cohabitants), including deceased relatives, were collected from a questionnaire and review of medical records. Mortality was compared among heFH patients, nonheFH patients, and nonconsanguineous family members. Results A total of 813 family members were analysed, 26.4% of whom were deceased. Among the deceased, the mean age of death was 69.3 years in heFH individuals, 73.5 years in nonheFH individuals, and 73.2 years in nonconsanguineous individuals, without significant differences. CVD was the cause of death in 59.7% of heFH individuals, 37.7% of nonheFH individuals, and 37.4% of nonconsanguineous individuals (P = 0.012). These differences were greater after restricting the analyses to parents. The hazard ratio of dying from CVD was 2.85 times higher (95% CI, (1.73–4.69) in heFH individuals than in individuals in the other two groups (non-FH and nonconsanguineous), who did not differ in their risk. Conclusions CVD mortality in heFH individuals is lower and occurs later than that described in the last century but is still higher than that in non-FH individuals. This improved prognosis of CVD risk is not associated with changes in non-CVD mortality

Moderate alcohol drinking is not associated with risk of depression in older adults

The scarce research on the effects of moderate alcohol consumption on mental health among older adults suggests a protective effect against depression. We prospectively examined the association between patterns of moderate alcohol consumption, depression and psychological distress, using information from 5, 299 community-dwelling older adults from the ELSA and Seniors-ENRICA cohorts. A Mediterranean drinking pattern (MDP) was defined as moderate alcohol intake (<40 g/day for men; <24 g/day for women) with a preference for wine and drinking only with meals. Depression was ascertained with the 10-item Geriatric Depression Scale (GDS-10), a self-report of clinically-diagnosed depression, or being on anti-depressant medication (Seniors-ENRICA); and with the 8-item Center for Epidemiologic Studies Depression Scale (CES-D) (ELSA). Psychological distress was assessed with the General Health Questionnaire-12 (GHQ-12). Compared to never drinkers, moderate drinkers showed comparable scores on the ENRICA-GDS-10 (PRR (95%CI): 1.03 (0.84–1.26)), the ENRICA-GHQ-12 (0.88 (0.73–1.06)), the ELSA-CES-D (0.92 (0.79–1.06)) and the ELSA-GHQ-12 (0.75 (0.55–1.01). The MDP was not associated with the GDS-10 or GHQ-12 scores, or with clinically-diagnosed depression; however drinkers with a preference for wine showed an increased number of psychological distress symptoms (1.31 (1.03–1.66)). In conclusion, we found no consistent protective association between moderate alcohol consumption and depression in older adults

Pautas espaciales en la evolución de la estructura agraria del Prepirineo oscense (1962-1999)

The spatial organisation of mediterranean mountain is highly affected by the evolution of the agricultural activities and structure. Demographic and socioeconomic changes during the last fifty years have led these areas to be disregarded; the abandonment of the traditional activities, which have modelled its landscapes, is one of the most outstanding effects. The study area: Prepirineo oscense, is used as an example of this situation. The recent evolution analysis of the agrarian structure, and its relationships with demographic transforrnations, will allow us to assess the intensity of the happened changes and its spatial behaviour.La organizaci&oacute;n espacial de la monta&ntilde;a mediterr&aacute;nea est&aacute; profundamente influida por la evoluci&oacute;n de la actividad agraria y en concreto por su estructura. Los cambios demogr&aacute;ficos y socioecon&oacute;micos acontecidos durante la segunda mitad del siglo XX han conducido a estas zonas a una situaci&oacute;n de marginaci&oacute;n; el abandono de la actividad tradicional modeladora de sus paisajes es una de las mas destacadas rnanifestaciones. El Prepirineo oscense, zona de estudio, es una muestra paradigm&aacute;tica de la situaci&oacute;n. El an&aacute;lisis de la evoluci&oacute;n reciente de su estructura agraria, as&iacute; como de sus ineludibles relaciones con la evoluci&oacute;n demogr&aacute;fica, permitir&aacute; valorar la intensidad de los cambios acontecidos y los patrones espaciales de comportamiento

Adjusting MtDNA quantification in whole blood for peripheral blood platelet and leukocyte counts

Alterations of mitochondrial DNA copy number (mtDNAcn) in the blood (mitochondrial to nuclear DNA ratio) appear associated with several systemic diseases, including primary mitochondrial disorders, carcinogenesis, and hematologic diseases. Measuring mtDNAcn in DNA extracted from whole blood (WB) instead of from peripheral blood mononuclear cells or buffy coat may yield different results due to mitochondrial DNA present in platelets. The aim of this work is to quantify the contribution of platelets to mtDNAcn in whole blood mtDNAcn(WB)] and to propose a correction formula to estimate leukocytes'' mtDNAcn mtDNAcn(L)] from mtDNAcn(WB). Blood samples from 10 healthy adults were combined with platelet-enriched plasma and saline solution to produce artificial blood preparations. Aliquots of each sample were combined with five different platelet concentrations. In 46 of these blood preparations, mtDNAcn was measured by qPCR. MtDNAcn(WB) increased 1.07 (95%CI 0.86, 1.29; p<0.001) per 1000 platelets present in the preparation. We proved that leukocyte count should also be taken into account as mtDNAcn(WB) was inversely associated with leukocyte count; it increased 1.10 (95%CI 0.95, 1.25, p<0.001) per unit increase of the ratio between platelet and leukocyte counts. If hematological measurements are available, subtracting 1.10 the platelets/leukocyte ratio from mtDNAcn(WB) may serve as an estimation for mtDNAcn(L). Both platelet and leukocyte counts in the sample are important sources of variation if comparing mtDNAcn among groups of patients when mtDNAcn is measured in DNA extracted from whole blood. Not taking the platelet/leukocyte ratio into account in whole blood measurements, may lead to overestimation and misclassification if interpreted as leukocytes'' mtDNAcn

Serum selenium concentrations and diabetes in U.S. adults : National Health and Nutrition Examination Survey (NHANES) 2003–2004

Background: Increasing evidence suggests that high selenium levels are associated with diabetes and other cardiometabolic risk factors. Objectives: We evaluated the association of serum selenium concentrations with fasting plasma glucose, glycosylated hemoglobin levels, and diabetes in the most recently available representative sample of the U.S. population. Methods: We used a cross-sectional analysis of 917 adults ≥ 40 years of age who had a fasting morning blood sample in the National Health and Nutrition Examination Survey 2003–2004. We evaluated the association of serum selenium, measured by inductively coupled plasma-dynamic reaction cell-mass spectrometry, and diabetes, defined as a self-report of current use of hypoglycemic agents or insulin or as fasting plasma glucose ≥ 126 mg/dL. Results: Mean serum selenium was 137.1 μg/L. The multivariable adjusted odds ratio [95% confidence interval (CI)] for diabetes comparing the highest quartile of serum selenium (≥ 147 μg/L) with the lowest (< 124 μg/L) was 7.64 (3.34–17.46). The corresponding average differences (95% CI) in fasting plasma glucose and glycosylated hemoglobin were 9.5 mg/dL (3.4–15.6 mg/dL) and 0.30% (0.14–0.46%), respectively. In spline regression models, the prevalence of diabetes as well as glucose and glycosylated hemoglobin levels increased with increasing selenium concentrations up to 160 μg/L. Conclusions: In U.S. adults, high serum selenium concentrations were associated with higher prevalence of diabetes and higher fasting plasma glucose and glycosylated hemoglobin levels. Given high selenium intake in the U.S. population, further research is needed to determine the role of excess selenium levels in the development or the progression of diabetes

The inflammatory potential of diet is related to incident frailty and slow walking in older adults

Background: Certain foods and dietary patterns have been associated with both inflammation and frailty. As chronic inflammation may play a role in frailty and disability, we examined the association of the inflammatory potential of diet with these outcomes. Methods: Data were taken from 1948 community-dwelling individuals =60 years old from the Seniors-ENRICA cohort, who were recruited in 2008–2010 and followed-up through 2012. Baseline diet data, obtained with a validated diet history, was used to calculate Shivappa's Dietary Inflammatory Index (DII), an “a priori” pattern score which is based on known associations of foods and nutrients with inflammation, and Tabung's Empirical Dietary Inflammatory Index (EDII), an “a posteriori” pattern score which was statistically derived from an epidemiological study. At follow-up, incident frailty was assessed with Fried's criteria, and incident limitation in instrumental activities of daily living (IADL) with the Lawton-Brody index. Statistical analyses were performed with logistic regression, and adjusted for the main confounders. Results: Compared with individuals in the lowest tertile of DII, those in the highest tertile showed higher risk of frailty (odds ratio [OR] 2.48; 95% confidence interval [CI]: 1.42, 4.44, p-trend = 0.001) and IADL disability (OR: 1.96; 95% CI: 1.03, 3.86, p-trend = 0.035). By contrast, EDII did not show an association with these outcomes. The DII score was associated with slow gait speed, both as a low score in the Short Physical Performance Battery test (OR: 1.82; 95% CI: 1.27, 2.62, p-trend = 0.001) and as a positive Fried's criterion (OR: 1.64; 95% CI: 1.08, 2.51, p-trend = 0.021), which use different thresholds. Conclusions: DII predicted frailty and IADL while EDII did not. DII is able to measure diet healthiness in terms of physical decline in addition to avoidance of inflammation

Glycated hemoglobin, fasting insulin and the metabolic syndrome in males. Cross-sectional analyses of the aragon workers health study baseline

Background and aims: Glycated hemoglobin (HbA1c) is currently used to diagnose diabetes mellitus, while insulin has been relegated to research. Both, however, may help understanding the metabolic syndrome and profiling patients. We examined the association of HbA1c and fasting insulin with clustering of metabolic syndrome criteria and insulin resistance as two essential characteristics of the metabolic syndrome. Methods: We used baseline data from 3200 non-diabetic male participants in the Aragon Workers' Health Study. We conducted analysis to estimate age-adjusted odds ratios (ORs) across tertiles of HbA1c and insulin. Fasting glucose and Homeostatic model assessment - Insulin Resistance were used as reference. Here we report the uppermost-to-lowest tertile ORs (95%CI). Results: Mean age (SD) was 48.5 (8.8) years and 23% of participants had metabolic syndrome. The ORs for metabolic syndrome criteria tended to be higher across HbA1c than across glucose, except for high blood pressure. Insulin was associated with the criteria more strongly than HbA1c and similarly to Homeostatic model assessment - Insulin Resistance (HOMA-IR). For metabolic syndrome, the OR of HbA1c was 2.68, of insulin, 11.36, of glucose, 7.03, and of HOMA-IR, 14.40. For the clustering of 2 or more non-glycemic criteria, the OR of HbA1c was 2.10, of insulin, 8.94, of glucose, 1.73, and of HOMA-IR, 7.83. All ORs were statistically significant. The areas under the receiver operating characteristics curves for metabolic syndrome were 0.670 (across HbA1c values) and 0.770 (across insulin values), and, for insulin resistance, 0.647 (HbA1c) and 0.995 (insulin). Among non-metabolic syndrome patients, a small insulin elevation identified risk factor clustering. Conclusions: HbA1c and specially insulin levels were associated with metabolic syndrome criteria, their clustering, and insulin resistance. Insulin could provide early information in subjects prone to develop metabolic syndrome

Oxidized LDL Is Associated With Metabolic Syndrome Traits Independently of Central Obesity and Insulin Resistance

This study assesses whether oxidative stress, using oxidized LDL (ox-LDL) as a proxy, is associated with metabolic syndrome (MS), whether ox-LDL mediates the association between central obesity and MS, and whether insulin resistance mediates the association between ox-LDL and MS. We examined baseline data from 3,987 subjects without diabetes in the Progression of Early Subclinical Atherosclerosis (PESA) Study. For the second, third, and fourth ox-LDL quartiles versus the first, the odds ratios (95% CI) for MS were 0.84 (0.52, 1.36), 1.47 (0.95, 2.32), and 2.57 (1.66, 4.04) (P < 0.001 for trend) once adjusted for age, sex, smoking, LDL-cholesterol, BMI, waist circumference, and HOMA-insulin resistance (HOMA-IR). Results showing the same trend were found for all MS components except glucose concentration. Ox-LDL mediated 13.9% of the association of waist circumference with triglycerides and only 1-3% of the association with HDL-cholesterol, blood pressure, and insulin concentration. HOMA-IR did not mediate the association between ox-LDL and MS components. This study found higher ox-LDL concentrations were associated with MS and its components independently of central obesity and insulin resistance. Ox-LDL may reflect core mechanisms through which MS components develop and progress in parallel with insulin resistance and could be a clinically relevant predictor of MS development.Y.H.-R. received support from Republic of Peru and the Inter-American Development Bank through FINCyT Science and Technology Program Scholarships No. 088-FINCyT-BDE-2014 under agreement 1663/OC-PE. M.L. received partial support from the Institute de Salud Carlos III, cofunded by the European Regional Development Fund/European Social Fund, "Investing in Your Future" grants PI10/00021 and PI14/00009. The PESA study is supported by a noncompetitive unrestricted grant shared between the CNIC and Santander Bank. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).S

Comparative efficacy between atorvastatin and rosuvastatin in the prevention of cardiovascular disease recurrence

Background: There is no randomized clinical trials with recurrence of atherosclerotic cardiovascular disease (ASCVD) as a major outcome with rosuvastatin. In order to analyze potential differences in the clinical response to atorvastatin and rosuvastatin in secondary ASCVD prevention, we have analyzed the clinical evolution of those subjects of the Dyslipemia Registry of the Spanish Society of Arteriosclerosis (SEA) who at the time of inclusion in the Registry had already suffered an ASCVD. Methods: This observational, retrospective, multicenter, national study was designed to determine potential differences between the use of atorvastatin and rosuvastatin in the ASCVD recurrence. Three different follow-up start-times were performed: time of inclusion in the registry; time of first event if this occurred after 2005, and time of first event without date restriction. Results: Baseline characteristics were similar between treatment groups. Among atorvastatin or rosuvastatin users, 89 recurrences of ASCVD were recorded (21.9%), of which 85.4% were coronary. At the inclusion of the subject in the registry, 345 participants had not suffered a recurrence yet. These 345 subjects accumulated 1050 person-years in a mean follow-up of 3 years. Event rates were 2.73 (95% CI: 1.63, 4.25) cases/100 person-years and 2.34 (95% CI: 1.17, 4.10) cases/100 person-years in the atorvastatin and rosuvastatin groups, respectively. There were no statistically significant differences between the two groups independently of the follow-up start-time. Conclusions: This study does not find differences between high doses of rosuvastatin and atorvastatin in the recurrence of ASCVD, and supports their use as clinically equivalent in secondary prevention of ASCVD

Cataract Surgery in Elderly Subjects with Heterozygous Familial Hypercholesterolemia in Prolonged Treatment with Statins

Background: Cataracts are the main cause of blindness and represent one fifth of visual problems worldwide. It is still unknown whether prolonged statin treatment favors the development of cataracts. We aimed to ascertain the prevalence of cataract surgery in elderly subjects with genetically diagnosed heterozygous familial hypercholesterolemia (HeFH) receiving statin treatment for ≥5 years, and compare this with controls. Methods: This is an observational, multicenter, case–control study from five lipid clinics in Spain. We collected data with the following inclusion criteria: age ≥65 years, LDL cholesterol levels ≥220 mg/dL without lipid-lowering drugs, a pathogenic mutation in a candidate gene for HeFH (LDLR, APOB, or PCSK9) and statin treatment for ≥5 years. Controls were selected from relatives of HeFH patients without hypercholesterolemia. Linear and logistic regressions based on generalized linear models and generalized estimating equations (GEE) were used. Cataract surgery was used as a proxy for cataract development. Results: We analyzed 205 subjects, 112 HeFH, and 93 controls, with a mean age of 71.8 (6.5) and 70.0 (7.3) years, respectively. HeFH subjects presented no difference in clinical characteristics, including smoking, hypertension, and type 2 diabetes mellitus, compared with controls. The mean duration of lipid-lowering treatment in HeFH was 22.5 (8.7) years. Cataract surgery prevalence was not significantly different between cases and controls. The presence of cataracts was associated neither with LDLc nor with the length of the statin therapy. Conclusion: In the present study, HeFH was not a risk factor for cataract surgery and prolonged statin treatment did not favor it either. These findings suggest that statin treatment is not related with cataracts