Vitamin D supplementation and COVID-19 risk: a population-based, cohort study.

PURPOSE: To analyze the associations between cholecalciferol or calcifediol supplementation, serum 25-hydroxyvitamin D (25OHD) levels and COVID-19 outcomes in a large population. METHODS: All individuals ≥ 18 years old living in Barcelona-Central Catalonia (n = 4.6 million) supplemented with cholecalciferol or calcifediol from April 2019 to February 2020 were compared with propensity score-matched untreated controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality occuring during the first wave of the pandemic. Demographical data, comorbidities, serum 25OHD levels and concomitant pharmacological treatments were collected as covariates. Associations between cholecalciferol or calcifediol use and outcome variables were analyzed using multivariate Cox proportional regression. RESULTS: Cholecalciferol supplementation (n = 108,343) was associated with slight protection from SARS-CoV2 infection (n = 4352 [4.0%] vs 9142/216,686 [4.2%] in controls; HR 0.95 [CI 95% 0.91-0.98], p = 0.004). Patients on cholecalciferol treatment achieving 25OHD levels ≥ 30 ng/ml had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19 and lower COVID-19 mortality than unsupplemented 25OHD-deficient patients (56/9474 [0.6%] vs 96/7616 [1.3%]; HR 0.66 [CI 95% 0.46-0.93], p = 0.018). Calcifediol use (n = 134,703) was not associated with reduced risk of SARS-CoV2 infection or mortality in the whole cohort. However, patients on calcifediol treatment achieving serum 25OHD levels ≥ 30 ng/ml also had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19, and lower COVID-19 mortality compared to 25OHD-deficient patients not receiving vitamin D supplements (88/16276 [0.5%] vs 96/7616 [1.3%]; HR 0.56 [CI 95% 0.42-0.76], p < 0.001). CONCLUSIONS: In this large, population-based study, we observed that patients supplemented with cholecalciferol or calcifediol achieving serum 25OHD levels ≥ 30 ng/ml were associated with better COVID-19 outcomes.

Halo effect of a Mediterranean-lifestyle weight-loss intervention on untreated family members' weight and physical activity: a prospective study.

OBJECTIVES: Obesity is subject to strong family clustering. The relatives of participants in weight-loss interventions may also modify their lifestyle and lose weight. The aim of this study was to examine the presence and magnitude of a halo effect in untreated family members of participants enrolled in a randomized, multi-component, lifestyle intervention. METHODS: A total of 148 untreated adult family members of participants in an intensive weight-loss lifestyle intervention (the PREDIMED-Plus study) were included. Changes at 1 and 2 years in body weight, physical activity, and adherence to a traditional Mediterranean diet (MedDiet) were measured. Generalized linear mixed models were used to assess whether the change differed between family members of the intervention group compared to the control. RESULTS: Untreated family members from the intervention group displayed a greater weight loss than those from the control after 1 and 2 years: adjusted 2-year weight change difference between groups was -3.98 (SE 1.10) kg (p < 0.001). There was a halo effect with regard to adherence to the MedDiet at one year which was sustained at two years: 2-year adjusted difference in MedDiet score change +3.25 (SE 0.46) (p < 0.001). In contrast, no halo effect was observed with regard to physical activity, as the untreated family members did not substantially modify their physical activity levels in either group, and the adjusted difference at two years between the 2 groups was -272 (SE 624) METs.min/week (p = 0.665). CONCLUSIONS: In the first prospective study to assess the influence on untreated family members of a diet and physical activity weight-loss intervention, we found evidence of a halo effect in relatives on weight loss and improvement in adherence to a MedDiet, but not on physical activity. The expansion of MedDiet changes from individuals involved in a weight-loss intervention to their family members can be a facilitator for obesity prevention.

Carotid atherosclerosis in virologically suppressed HIV patients: comparison with a healthy sample and prediction by cardiovascular risk equations.

OBJECTIVES: To compare the prevalence of carotid atherosclerosis in virologically suppressed HIV patients with that of a community sample, and to evaluate the capacity of various cardiovascular risk (CVR) equations for predicting carotid atherosclerosis. METHODS: This was a cross-sectional study with two randomly selected groups: HIV patients from an HIV unit and a control group drawn from the community. Participants were matched by age (30-80 years) and sex without history of cardiovascular disease. Carotid plaque, common carotid intima-media thickness (cc-IMT) and subclinical atherosclerosis (carotid plaque and/or cc-IMT > 75th percentile) were assessed by carotid ultrasound. The Systematic Coronary Risk Evaluation (SCORE), Framingham, REGICOR, reduced Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D), and COMVIH equations were applied, and their abilities to predict carotid plaque were compared using the area under the curve (AUC). RESULTS: Each group included 379 subjects (77.8% men, age 49.7 years). Duration of antiretroviral therapy was 15.5 years. There were no differences between the groups for carotid plaque (HIV, 33.2%; control, 31.3%), mean cc-IMT (HIV, 0.63 mm; control, 0.61 mm) or subclinical atherosclerosis (HIV, 42.9%; control, 47.9%). Thymidine analogues were independently associated with subclinical atherosclerosis in HIV-infected patients. CVR equations revealed AUCs between 0.715 and 0.807 for prediction of carotid plaque; prediction was better in the control group and did not improve when HIV-adapted scales were used. CONCLUSIONS: The features of carotid atherosclerosis did not differ between the HIV-infected and the control group, although CVR equations were more predictive for carotid plaque in controls than in HIV-infected patients. HIV-specific equations did not improve prediction.

Prognostic Value of Inflammatory Biomarkers in 5-Year Survival After Endovascular Repair of Abdominal Aortic Aneurysms in a Predominantly Male Cohort: Implications for Practice.

BACKGROUND: Prognostic factors of long-term survival can guide selection of patients for endovascular repair of abdominal aortic aneurysms (EVAR). The aim of this study was to evaluate the relationship between the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR) and the systemic immune-inflammation index (SIII) with survival after EVAR and to assess whether the addition of these biomarkers improved the prediction of survival after surgery. METHODS: Retrospective analysis of 284 consecutive patients who underwent an EVAR at a single institution. The association between biomarkers and survival was explored using generalized additive models with penalized smoothing splines and multivariate Cox models. C-statistics and continuous net reclassification indexes (c-NRI) were used to assess the improvement in prediction. RESULTS: Survival rates at 2 and 5 years were 83.9% and 66.2%, respectively. The predictive score of survival included hemoglobin (HR = 0.849, p = 0.004), statin intake (HR = 0.538, p = 0.004), atrial fibrillation (HR = 2.515, p < 0.001), heart failure (HR = 2.542, p = 0.017) and the non-revascularized coronary artery disease (HR = 2.163, p = 0.004). Spline analyses showed a linear relationship between survival and NLR, PLR, LMR and SII. After adjusting for the predictive score, there was an independent relationship between survival and NLR (HR = 1.072, p = 0.006), PLR (HR = 1.002, p = 0.014) and SII (HR = 1.000, p = 0.043). However, only the addition of NLR improved moderately the c-NRI. A NLR ≥ 3 was independently associated with lower survival rates at 2-years (HR 1.98; 95% CI 1.07-3.66) and 5-years (HR 1.84, 95% CI 1.22-2.78) of follow-up. CONCLUSIONS: Most inflammatory biomarkers are linear and independently associated with survival after EVAR, but only the NLR improved moderately the prediction of a survival score. Therefore, a NLR ≥ 3 may be used to identify patients with a low survival rate and help in decision-making.

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.

Lipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is not only an inherited but also modifiable epigenetic mark that has been related to cardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina Human Methylation 450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n = 645) and validation in the Framingham Offspring Study (n = 2,542). Fourteen CpG sites located in nine genes (SREBF1, SREBF2, PHOSPHO1, SYNGAP1, ABCG1, CPT1A, MYLIP, TXNIP and SLC7A11) and 2 intergenic regions showed differential methylation in association with lipid traits. Six of these genes and 1 intergenic region were new discoveries showing differential methylation related to total cholesterol (SREBF2), HDL-cholesterol (PHOSPHO1, SYNGAP1 and an intergenic region in chromosome 2) and triglycerides (MYLIP, TXNIP and SLC7A11). These CpGs explained 0.7%, 9.5% and 18.9% of the variability of total cholesterol, HDL cholesterol and triglycerides in the Framingham Offspring Study, respectively. The expression of the genes SREBF2 and SREBF1 was inversely associated with methylation of their corresponding CpGs (P-value = 0.0042 and 0.0045, respectively) in participants of the GOLDN study (n = 98). In turn, SREBF1 expression was directly associated with HDL cholesterol (P-value = 0.0429). Genetic variants in SREBF1, PHOSPHO1, ABCG1 and CPT1A were also associated with lipid profile. Further research is warranted to functionally validate these new loci and assess the causality of new and established associations between these differentially methylated loci and lipid metabolism.

Sex-related differences in abdominal obesity impact on ischemic stroke risk.

BACKGROUND AND PURPOSE: The objective of our study was to evaluate sex differences in the impact of weight and abdominal obesity on the risk of ischemic stroke. METHODS: We included 388 patients with ischemic stroke (aged <75 years) assessed consecutively in our hospital and 732 controls matched by age and sex. Vascular risk factors and anthropometric data (waist circumference, weight and height) were recorded. The impact of three anthropometric variables [body mass index (BMI), waist circumference and waist to height ratio] on ischemic stroke risk was calculated. These variables were divided into quartiles for a comprehensive comparison between cases and controls, stratified by sex and adjusted in logistic regression by age and vascular risk factors. Further logistic regression using dummy variables was performed to evaluate the association between BMI-adjusted abdominal obesity and stroke risk. RESULTS: Increased BMI was not associated with increased stroke risk overall or in women, but was a protective factor in men [P = 0.03; odds ratio (OR), 0.59 (0.37-0.94)]. Abdominal obesity was a risk factor for stroke in women, in both waist circumference [P < 0.001; OR, 5.79 (3.10-10.85)] and waist to height ratio [P < 0.001; OR, 3.61 (1.99-6.54)] analyses, but was not significant in men. When considered independently of BMI, abdominal obesity was a risk factor in both sexes, but the strength of the association was significantly higher in women. CONCLUSIONS: Increased BMI was related to a lower risk of stroke in men. Abdominal obesity was associated with ischemic stroke in women. The impact of abdominal obesity on stroke risk differs by sex.

In-hospital prognosis and long-term mortality of STEMI in a reperfusion network. "Head to head" analisys: invasive reperfusion vs optimal medical therapy.

BACKGROUND: ST Segment Elevation Acute myocardial infarction (STEMI) preferred treatment is culprit artery reperfusion with primary percutaneous coronary intervention (PPCI). We ought to analyze the benefit of early reperfusion vs. optimal medical therapy in STEMI before and after the set-up of a regional STEMI network that prioritizes PPCI. METHODS: Between January 2002 and December 2013, 1268 STEMI patients were consecutively admitted in a University Hospital. Patients were classified in two groups: pre-STEMI Network (January 2002-June 2009; n = 670) and post-STEMI network (July 2009-December 2013; n = 598). Vital status was available at 2-year follow-up. RESULTS: The STEMI network increased reperfusion (89.2% vs 64.4%, p < 0.001) mainly using PCI (99.0% vs 43.9%, p < 0.001). In univariate analysis, in-hospital mortality was significantly lower in the post-STEMI network period (2.51% vs. 7.16%, p < 0.001). After multivariate adjustment, including age, sex, comorbidities, severity and reperfusion therapy, a trend to a lower in-hospital mortality was observed (post-Network OR: 0.50, 95% CI:0.16-1.59, p = 0.24); this trend disappeared when optimal medical therapy was included in the model (post-Network OR: 1.14, 95% CI:0.32-4.08, p = 0.840). No differences in 2-year mortality were observed (post-Network HR: 0.83; CI 95%: 0.55-1.25, p = 0.37). CONCLUSION: A STEMI network with PPCI 24/7 improved reperfusion therapy, resulting in an increase on PPCI. Despite in-hospital mortality decreased with a STEMI network, 2-year mortality remained similar in both periods, pre- and post-Network. Optimal medical therapy could be as important as reperfusion therapy in a STEMI reperfusion network.

Influence of fetal glutathione S-transferase copy number variants on adverse reproductive outcomes.

A nested case-control association study was designed to investigate the influence of maternal and fetal copy number variants (CNVs) on reproductive outcomes. Genotypes of ten CNVs encompassing GST and CYP genes were assessed. Significant associations were only found for child CNV genotypes. In particular, the child GSTM1 insertion allele was associated with prematurity protection (odds ratio, 95% CI: 0.67, 0.51-0.89; P < 0.01), whereas the child GSTT2B insertion allele was associated with an increased risk of being small for gestational age (odds ratio, 95% CI: 1.33, 1.07-1.67; P = 0.01). The study highlights the role of the fetal genome in prenatal development and also the need to analyse CNVs in a systematic manner.

A cost-utility analysis of increasing percutaneous coronary intervention use in elderly patients with acute coronary syndromes in six European countries.

AIMS: Percutaneous coronary intervention reduces mortality in acute coronary syndrome patients but the cost-utility of increasing its use in elderly acute coronary syndrome patients is unknown. METHODS: We assessed the efficiency of increased percutaneous coronary intervention use compared to current practice in patients aged ≥75 years admitted for acute coronary syndrome in France, Germany, Greece, Italy, Portugal and Spain with a semi-Markov state transition model. In-hospital mortality reduction estimates by percutaneous coronary intervention use and costs were derived from the EUROpean Treatment & Reduction of Acute Coronary Syndromes cost analysis EU project (n = 28,600). Risk of recurrence and out-of-hospital all-cause mortality were obtained from the Information System for the Development of Research in Primary Care (SIDIAP) database from North-Eastern Spain (n = 55,564). In-hospital mortality was modelled using stratified propensity score analysis. The 8-year acute coronary syndrome recurrence risk and out-of-hospital mortality were estimated with a multistate survival model. The scenarios analysed were to increase percutaneous coronary intervention use among patients with the highest, moderate and lowest probability of receiving percutaneous coronary intervention based on the propensity score analysis. RESULTS: France, Greece and Portugal showed similar total costs/1000 individuals (7.29-11.05 m €); while in Germany, Italy and Spain, costs were higher (13.53-22.57 m €). Incremental cost-utility ratios of providing percutaneous coronary intervention to all patients ranged from 2262.8 €/quality adjusted life year gained for German males to 6324.3 €/quality adjusted life year gained for Italian females. Increasing percutaneous coronary intervention use was cost-effective at a willingness-to-pay threshold of 10,000 €/quality adjusted life year gained for all scenarios in the six countries, in males and females. CONCLUSION: Compared to current clinical practice, broadening percutaneous coronary intervention use in elderly acute coronary syndrome patients would be cost-effective across different healthcare systems in Europe, regardless of the selected strategy.

Outcome of intracerebral haemorrhage patients pre-treated with statins.

BACKGROUND: Statins treatment may have potential clinical impact in vascular disease beyond cholesterol lowering. Its benefits have been documented in cerebral ischaemia and in subarachnoid haemorrhage. In intracerebral haemorrhage (ICH), experimental models in statin-treated animals have better outcome than non-treated ones, but in humans the relationship is unclear. We investigated whether patients treated with statins before the onset of intracerebral haemorrhage have a better outcome at 3 months than patients without statins pre-treatment. METHODS: Retrospective review of primary intracerebral haemorrhage case series from a prospective stroke register. We recorded demographics, vascular risk factors, previous statin treatment, Glasgow coma scale (GCS) at onset, ICH scale, hematoma volume and location, ventricular extension of the hematoma, and functional outcome at 3 months. The effect of prior statin treatment on good outcome (modified Rankin scale [mRS] 0 to 2) was analysed by logistic regression analysis. RESULTS: We included 269 patients (age 71.9 +/- 12.4, mean +/- SD, 152 males). Thirty-four patients (12.6%) were on prior statin treatment when admitted. There were no differences in fasting serum cholesterol and triglycerides levels between the statin pre-treated groups and the group without statin pre-treatment. Multivariate regression analysis showed a significant association between age (OR: 0.95; CI 0.92-0.97), ICH volume (OR: 0.96; CI 0.94-0.98), GCS (OR: 1.55; CI 1.21-1.98), pre-treatment with statins (OR: 4.21; CI 1.47-12.17; P = 0.008), and good outcome at 3 months. CONCLUSIONS: Statins pre-treatment of patients with intracerebral haemorrhage may provide better functional outcome at 3 months of acute onset.

Prevalence of symptomatic and asymptomatic peripheral arterial disease and the value of the ankle-brachial index to stratify cardiovascular risk.

OBJECTIVES: To determine the prevalence of ankle-brachial index (ABI)<0.9 and symptomatic peripheral arterial disease (PAD), association with cardiovascular risk factors (CVRF), and impact of adding ABI measurement to coronary heart disease (CHD) risk screening. DESIGN: Population-based cross-sectional survey of 6262 participants aged 35-79 in Girona, Spain. METHODS: Standardized measurements (CVRF, ABI, 10-year CHD risk) and history of intermittent claudication (IC), CHD, and stroke were recorded. ABI<0.9 was considered equivalent to moderate-to-high CHD risk (> or =10%). RESULTS: ABI<0.9 prevalence was 4.5%. Only 0.62% presented low ABI and IC. Age, current smoker, cardiovascular disease, and uncontrolled hypertension independently associated with ABI<0.9 in both sexes; IC was also associated in men and diabetes in women. Among participants 35-74 free of cardiovascular disease, 6.1% showed moderate-to-high 10-year CHD risk; adding ABI measurement yielded 8.7%. Conversely, the risk function identified 16.8% of these participants as having 10-year CHD risk>10%. In participants 75-79 free of cardiovascular disease, the prevalence of ABI<0.9 (i.e., CHD risk> or =10%) was 11.9%. CONCLUSIONS: ABI<0.9 is relatively frequent in those 35-79, particularly over 74. However, IC and CHD risk> or =10% indicators are often missing. Adding ABI measurement to CHD-risk screening better identifies moderate-to-high cardiovascular risk patients.

Weather as a trigger of stroke. Daily meteorological factors and incidence of stroke subtypes.

BACKGROUND: The conclusions of previous studies show little agreement concerning the relationship between weather and the incidence of stroke. We analyse the relationship between daily meteorological conditions and daily as well as seasonal stroke incidence. METHODS: 1,286 consecutive strokes assessed during 3 years (2001-2003) from the reference area of Hospital del Mar were classified as intracerebral haemorrhage (ICH) (n = 243) or ischaemic stroke (IS) (n = 1,043). IS was divided in non-lacunar stroke (NLS) (n = 732) and lacunar stroke (LS) (n = 311). Daily meteorological data were obtained from 'Observatori Fabra' of Barcelona: atmospheric pressure (AP), relative humidity, maximum, minimum, and mean temperatures, and the variation of all these measures compared with the previous day. RESULTS: Total stroke (TS) incidence showed little association with AP (coefficient of confidence, CC: -0.072; p = 0.022), but was higher with the AP variations (CC: 0.127; p < 0.001). NLS were related to AP falls (OR: 2.41; p < 0.001) whilst ICHs were associated with AP rises (OR: 2.07; p = 0.01). NLS and temperature showed an inverse correlation; however, it lost its significance after adjusting for AP variations. The daily incidences of NLS and ICH were higher in autumn and in winter, but depended strongly on the daily variations of AP. No other associations were found. CONCLUSIONS: The incidences of NLS and ICH are related to AP changes compared with the previous day. AP changes largely explain the seasonal and daily variations in the incidence of stroke. These data may help to explain the controversy in previous studies and to promote studies focused on the trigger mechanisms of stroke.