Increased risk of arrhythmias, heart failure, and thrombosis in SARS-CoV-2 positive individuals persists at one year post-infection.

Risk of cardiovascular events is increased after COVID-19. However, information on cardiovascular risk trends after COVID-19 infection is lacking and estimates by sex are inconsistent. Our aim was to examine cardiovascular outcomes and mortality in a large cohort (164,346 participants) of SARS-CoV-2 positive individuals compared to non-positive individuals, stratified by sex. Data were obtained from the Spanish Health System's electronic medical records. Selected individuals were ≥ 45 years old with/without a positive SARS-CoV-2 test in the period March-May 2020. Follow-up was obtained until January 31, 2021, for cardiovascular events (angina/myocardial infarction, arrhythmias, bypass/revascularization, heart failure, peripheral artery disease, stroke/transient ischemic attack, and thrombosis), and until March 31, 2021, for mortality. Individuals were matched by propensity score. Incidence of cardiovascular events and mortality was compared with accelerated failure time models. The effect of matching and of COVID-19 severity was assessed with sensitivity analyses. In the first 3 months of follow-up, SARS-CoV-2 positive individuals had a higher risk of mortality and of all cardiovascular events. From 4-12 months, there was increased risk of mortality in SARS-CoV-2 positive individuals overall, of heart failure in SARS-CoV-2 positive females (HR= 1.26 [1.11-1.42]), and of arrhythmias and thrombosis in SARS-CoV-2 positive males (HR= 1.29 [1.14-1.47] and HR= 1.35 [1.03-1.77], respectively). When COVID-19 patients admitted to the ICU were excluded, incidence of thrombosis was similar in males regardless of positive/non-positive SARS-CoV-2 status. In the full year of follow-up, increased incidence of heart failure and of arrhythmias and thrombosis was observed in SARS-CoV-2 positive females and males, respectively.

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.

Prevalencia e incidencia de hiperpotasemia en población española con insuficiencia cardiaca con fracción de eyección deprimida: revisión sistemática y relevancia poblacional / Prevalence and incidence of hyperkalaemia in the Spanish population with heart failure with reduced ejection fraction: a systematic review and populational relevance

Antecedentes y objetivo: La hiperpotasemia (K+≥5,5mmol/l) es un desequilibrio iónico grave cuando aparece en pacientes que padecen insuficiencia cardiaca con fracción de eyección deprimida (ICFED), ya que incrementa el riesgo de fibrilación ventricular. No existen estimaciones del número de pacientes que sufren esta complicación. El objetivo de este estudio fue estimar la prevalencia e incidencia de hiperpotasemia en pacientes con ICFED en España. Materiales y métodos: A partir de una búsqueda bibliográfica sistemática se calculó mediante un metaanálisis la prevalencia de ICFED<40% en población europea y norteamericana. A partir de otra búsqueda bibliográfica sistemática se calculó la prevalencia de hiperpotasemia en individuos con insuficiencia cardiaca, así como su incidencia anual. Considerando los anteriores valores y la pirámide de población española en 2016 se estimó el número de individuos con ICFED que presentan actualmente y que desarrollan cada año hiperpotasemia en España. Resultados: Alrededor de 17.100 individuos (10.000 hombres y 7.100 mujeres) de los 508.000 pacientes con ICFED presentan hiperpotasemia en España. Asimismo, unos 14.900 pacientes con ICFED (9.500 hombres y 5.400 mujeres) la desarrollan cada año. Conclusiones: Aproximadamente uno de cada 30 pacientes con ICFED presenta valores plasmáticos de potasio por encima de 5,5mmol/l

Background and objectives: Hyperkalaemia (K+ levels≥5.5mmol/L) is a severe ion imbalance that occurs in patients who have heart failure (HF) with reduced ejection fraction (HFrEF) and increases the risk of ventricular fibrillation. Given that there are no estimates on the number of patients with this complication, the aim of this study was to estimate the prevalence and incidence of hyperkalaemia in patients with HFrEF in Spain. Material and methods: Based on a systematic literature search and through a meta-analysis, we calculated an HFrEF prevalence of ≤40% in the European and U.S. population. Based on another systematic literature search, we calculated the prevalence of hyperkalaemia in patients with HF and its annual incidence rate. Considering the previous values and the Spanish population pyramid in 2016, we estimated the number of individuals with HFrEF who currently have hyperkalaemia and those who develop it each year in Spain. Results: Approximately 17,100 (10,000 men and 7100 women) of the 508,000 patients with HFrEF in Spain have hyperkalaemia. Furthermore, approximately 14,900 patients with HFrEF (9500 men and 5400 women) develop hyperkalaemia each year. Conclusions: Approximately 1 of every 30 patients with HFrEF has plasma potassium values >5.5 mmol/L

Prevalence and incidence of hyperkalaemia in the Spanish population with heart failure with reduced ejection fraction: a systematic review and populational relevance. / Prevalencia e incidencia de hiperpotasemia en población española con insuficiencia cardiaca con fracción de eyección deprimida: revisión sistemática y relevancia poblacional.

BACKGROUND AND OBJECTIVES: Hyperkalaemia (K+ levels≥5.5mmol/L) is a severe ion imbalance that occurs in patients who have heart failure (HF) with reduced ejection fraction (HFrEF) and increases the risk of ventricular fibrillation. Given that there are no estimates on the number of patients with this complication, the aim of this study was to estimate the prevalence and incidence of hyperkalaemia in patients with HFrEF in Spain. MATERIAL AND METHODS: Based on a systematic literature search and through a meta-analysis, we calculated an HFrEF prevalence of ≤40% in the European and U.S. POPULATION: Based on another systematic literature search, we calculated the prevalence of hyperkalaemia in patients with HF and its annual incidence rate. Considering the previous values and the Spanish population pyramid in 2016, we estimated the number of individuals with HFrEF who currently have hyperkalaemia and those who develop it each year in Spain. RESULTS: Approximately 17,100 (10,000 men and 7100 women) of the 508,000 patients with HFrEF in Spain have hyperkalaemia. Furthermore, approximately 14,900 patients with HFrEF (9500 men and 5400 women) develop hyperkalaemia each year. CONCLUSIONS: Approximately 1 of every 30 patients with HFrEF has plasma potassium values >5.5 mmol/L.

Abnormally High Ankle-Brachial Index is Associated with All-cause and Cardiovascular Mortality: The REGICOR Study.

INTRODUCTION: The clinical significance of a high ankle brachial index (ABI) and its relationship to cardiovascular disease (CVD) and mortality is controversial. The aim of this study was to estimate the association between abnormally high ABI ≥ 1.4 and coronary heart disease (CHD), cerebrovascular disease, and all-cause mortality in a Mediterranean population without CVD. METHODS: A prospective population based cohort study of 6352 subjects was followed up for a median 6.2 years. Subjects under 35 years, with a history of CVD or an ABI < 0.9 were excluded. All CHD events (angina, myocardial infarction, coronary revascularisation), cerebrovascular events (stroke, transient ischaemic attack), and all-cause mortality were recorded. RESULTS: A total of 5679 subjects fulfilled the inclusion criteria, of which 5517 (97.1%) had a normal ABI whereas 162 (2.9%) had an ABI ≥ 1.4. The profile of individuals with abnormally high ABI revealed as independent related factors age (OR = 1.0; p = .045), female sex (OR = 0.4; p < .01), diabetes (OR = 1.9; p = .02), and lower diastolic blood pressure (OR = 0.9; p < .001). During follow-up 309 (5.4%) participants presented with a CV event and 286 (5.0%) died. An ABI ≥ 1.4 was associated with a higher incidence of CV events in the univariate (HR = 1.7) but not in the multivariate survival Cox regression analysis. An ABI ≥ 1.4 was independently associated with all-cause mortality (HR = 2.0; IC 95% 1.32-2.92) and cardiovascular mortality (HR = 3.1; IC 95% 1.52-6.48). CONCLUSIONS: In subjects without CVD, those with abnormally high ABI do not have a greater CV event rate than those with a normal ABI. However, there seems to be a trend towards higher mortality risk, supporting the guidelines that consider this subgroup to be a high risk population.

Peripheral Arterial Disease Incidence and Associated Risk Factors in a Mediterranean Population-based Cohort. The REGICOR Study.

OBJECTIVES: The reported incidence of lower extremity peripheral arterial disease (PAD) in Western countries ranges between 530 and 2,380 per 100,000 person years. The aims of this study were to determine the incidence of PAD and identify associated risk factors in a Mediterranean population. METHODS: Cardiovascular risk factors, the Edinburgh questionnaire, and ankle brachial index (ABI) were collected from 5,434 individuals, aged 35-79 years, from a population based cohort study at baseline and after a mean of 5.7 years follow up. PAD was defined as ABI <0.9 or a clinical diagnosis during follow up. Logistic and regression tree analyses were used to identify factors associated with PAD. RESULTS: In total, 118 new cases of confirmed PAD were identified. The cumulative population incidence rate of PAD was 377 cases per 100,000 person years. For symptomatic PAD, this figure was 102 per 100,000 person years. The most important risk factors for PAD were current (OR 2.30; 95% CI 1.27-4.16) or former smoking (OR 2.02; 95% CI 1.19-3.43), diabetes (OR 1.78; 95% CI 1.17-2.72), age (OR 1.04; 95% CI 1.02-1.07), history of cardiovascular disease (OR 2.06; 95% CI 1.22-3.51), triglycerides level (OR 1.56; 95% CI 1.07-2.29), and systolic blood pressure (OR 1.02; 95% CI 1.01-1.03). In the population ≤65 years the most relevant risk factor was diabetes, whereas in those >65 years smoking was the leading factor. Long-term uncontrolled diabetes was the strongest risk factor for PAD (OR 10.14; 95% CI 3.57-28.79). CONCLUSION: The incidence of lower extremity PAD is lower in the Mediterranean area than has been reported for other areas. The data suggest that patients with long-term uncontrolled diabetes and former and current smokers older than 65 years should be considered for PAD screening.

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.

Adding low ankle brachial index to classical risk factors improves the prediction of major cardiovascular events. The REGICOR study.

OBJECTIVES: Cardiovascular risk estimation is a key element of current primary prevention strategies, despite its limited accuracy. Several biomarkers are being tested to assess their capacity to improve coronary (CHD) and cardiovascular (CVD) prediction. One of these biomarkers is ankle brachial index (ABI). The aim of this study was to assess whether the inclusion of ABI improved the predictive capacity of the Framingham-REGICOR risk function in an area of low CVD incidence. METHODS: A total of 5248 individuals, aged 35-74 years, from a prospective population-based cohort study were followed up for a median 5.9 years. Baseline ABI was measured using a standardized method. All incident CHD (angina, myocardial infarction, coronary revascularization, CHD death) and CVD (also including fatal and non-fatal stroke) events were recorded. Improvements in discrimination (ΔC-statistics) and reclassification by net reclassification index (NRI) were assessed. RESULTS: During follow-up, 111 and 64 subjects presented with a coronary or cerebrovascular event. Pathological ABI (≤0.9) was associated with increased CHD and CVD risk (HR: 2.08 and HR: 2.24, respectively; p-value<0.001). Including ABI in the Framingham-REGICOR function improved both its discrimination and its reclassification capacity for CVD events but not for CHD events; the ΔC-statistic for CVD events was 0.007 (95% Confidence Interval: 0.001; 0.017) and the NRI was 0.029 (95% CI: 0.014-0.045; p-value<0.001). CONCLUSION: Inclusion of the ABI improves the predictive capacity of the Framingham-REGICOR risk function. The study results indicate the potential value of including this simple test in cardiovascular risk stratification and support current guidelines recommendations.

Prevalence of atrial fibrillation and its associated factors in Spain: An analysis of 6 population-based studies. DARIOS Study. / Prevalencia de fibrilación auricular y factores asociados en España, análisis de seis estudios de base poblacional. Estudio DARIOS.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is the most common type of arrhythmia. The purpose of this study was to determine the prevalence of atrial fibrillation and its relationship with cardiovascular risk factors in Spain. METHODOLOGY: Cross-sectional study based on a grouped analysis of 17,291 randomized individuals recruited in 6 population studies. RESULTS: The prevalence of atrial fibrillation was 1.5% (95% CI:1.3-1.7%). Men had a greater prevalence of the disease than women (1.9 vs. 1.1%, respectively). The prevalence of atrial fibrillation progressively increased with age: 0.05% for patients younger than 45 years, 0.5% for those between 45-59 years of age, 2.3% for those between 60-74 years of age and 6.3% for those older than 75 years. The percentage of individuals who were underwent anticoagulant treatment was 74.3%. The risk factors significantly associated with arrhythmia were an age older than 60 years (odds ratio [OR]: 7.6; 95% CI: 5.1-11.2), the male sex (OR:1.8; 95% CI: 1.4-2.4), arterial hypertension (OR:1.6; 95% CI: 1.2-2.1), obesity (OR:1.5; 95% CI:1.2-2.1) and a history of coronary artery disease (OR:1.9; 95% CI: 1.3-3.0). CONCLUSION: Atrial fibrillation is a common disease in elderly individuals, while its prevalence is low in individuals younger than 60 years. Most individuals with atrial fibrillation were on anticoagulant treatment. The risk factors for this type of arrhythmia are age, the male sex, hypertension, obesity and a history of coronary artery disease.

¿Podemos modernizar la prevención cardiovascular? / Can cardiovascular prevention be modernized?

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Derivation and validation of BOREAS, a risk score identifying candidates to develop cold-induced hypertension.

INTRODUCTION: Blood pressure increases in cold periods, but its implications on prevalence of hypertension and on individual progression to hypertension remain unclear. Our aim was to develop a pre-screening test for identifying candidates to suffer hypertension only in cold months among non-hypertensive subjects. METHODS: We included 95,277 subjects registered on a primary care database from Girona (Catalonia, Spain), with ≥ 3 blood pressure measures recorded between 2003 and 2009 and distributed in both cold (October-March) and warm (April-September) periods. We defined four blood pressure patterns depending on the presence of hypertension through these periods. A Cox model determined the risk to develop vascular events associated with blood pressure patterns. A logistic regression distinguished those nonhypertensive individuals who are more prone to suffer cold-induced hypertension. Validity was assessed on the basis of calibration (using Brier score) and discrimination (using the area under the receiver operating characteristics). RESULTS: In cold months, the mean systolic blood pressure increased by 3.3 ± 0.1 mmHg and prevalence of hypertension increased by 8.2%. Cold-induced hypertension patients were at higher vascular events risk (Hazard ratio=1.44 [95% Confidence interval 1.15-1.81]), than nonhypertensive individuals. We identified age, diabetes, body mass index and prehypertension as the major contributing factors to cold-induced hypertension onset. DISCUSSION: Hypertension follows a seasonal pattern in some individuals. We recommend screening for hypertension during the cold months, at least in those nonhypertensive individuals identified as cold-induced hypertensive by this assessment tool.

Infrapopliteal arterial occlusive disease in elderly men: a population based study.

AIM: The aim of this paper was to determine prevalence, cardiovascular risk factors and association with coronary heart disease (CHD) of isolated infrapopliteal arterial disease in old-adult men. DESIGN: cross-sectional; participants: population-based sample of 699 men aged 55 to 74 years, measurements: cardiovascular history and risk factors, electrocardiogram, segmental pressures and velocity waveforms in lower limbs. RESULTS: Peripheral arterial occlusive disease (PAOD) was observed in 13.4% subjects, of whom 39.4% (37 patients) had isolated infrapopliteal PAOD. Of these, 11 (29.7%) patients were symptomatic. Isolated infrapopliteal PAOD was significantly associated with increased age, smoking, diabetes and hypertriglyceridemia. Subjects with extended PAOD differed from those with isolated infrapopliteal PAOD in increased tobacco exposure, higher levels of LDL and lower levels of HDL cholesterol. Association between PAOD and CHD was almost always significant (odds ratio from 1.8 to 3.4) irrespective of PAOD topographic pattern and symptom characteristics of CHD subjects. CONCLUSION: Isolated infrapopliteal PAOD is a frequent asymptomatic disorder in old-adult men, clearly associated with both symptomatic and asymptomatic CHD. In contrast to an expected risk factor profile biased by clinical practice, these subjects only differed from those with PAOD significantly extended to proximal arteries in their smoking exposition and a more atherogenic lipid profile.

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.

Prevalence of peripheral artery disease and its associated risk factors in Spain: The ESTIME Study.

AIM: Several studies have demonstrated that patients with peripheral arterial disease (PAD), are at an increased risk of morbidity and mortality compared with those without PAD. However, few population-based studies have addressed the prevalence of PAD and intermittent claudication (IC). We assessed the prevalence of and the factors associated with PAD and IC in the Spanish population. METHODS: A cross sectional study with 1324 participants aged 55 to 84 years randomly selected from the census was conducted in 12 Spanish regions. The presence of PAD and IC was determined by an ankle-brachial index (ABI) <0.90 in either leg and by means of the Edinburgh questionnaire, respectively, fulfilled together with a detailed past history. All participants had blood pressure, body mass index, glycemia, and lipid profile measured. RESULTS: The response rate was 63.9% (846/1 324). ABI prevalence of PAD was 8.03% The prevalence of symptoms of definite or atypical IC was 6%. Subjects with an ABI <0.9 were more likely to be older, men, diabetics, current smokers, with coronary heart disease, with higher systolic pressure and with higher triglyceride levels than participants with ABI 0.9. CONCLUSIONS: ESTIME study confirms the high prevalence of asymptomatic PAD, and its relation with typical cardiovascular risk factors. ABI provides early diagnosis before claudication symptoms in a high proportion of patients. ABI could contribute to developing early prevention programmes.

The association of peripheral arterial occlusive disease with major coronary events in a mediterranean population with low coronary heart disease incidence.

OBJECTIVES: The association of peripheral arterial occlusive disease (PAD) association with major coronary events (MCE) has been well documented, nevertheless data are lacking for populations with a low incidence of coronary heart disease (CHD). We aimed to assess the association of PAD with MCE in a Mediterranean population. DESIGN: Prospective survey of 699 55-74 year-old men representative of an urban district near Barcelona (Spain). METHODS: Baseline cardiovascular risk factors, CHD and PAD (ankle/brachial index<0.9) were recorded. MCE were evaluated during the 5-year follow-up. RESULTS: At recruitment 94 subjects (13.4%) had PAD. During follow-up (mean 69.3 months), 35 (5%) subjects suffered a MCE, of whom 12 had PAD, 9 previous symptomatic CHD and 1 subject both conditions. Higher CHD related mortality (8.6% vs 1.4%; p<0.001) and lower MCE-free survival (78.67% vs 93.26%; p<0.001) was observed for PAD subjects. On Cox regression analysis PAD (RR=3; p=0.003) and previous symptomatic CHD (RR=4.1; p<0.001) were associated independently with MCE during follow-up. CONCLUSIONS: Even in a population with a low incidence of CHD there is a strong relationship between PAD and future MCE. Screening for PAD may improve the selection of patients targeted for cardiovascular risk prevention.