Measuring Cardiorespiratory Fitness without Exercise Testing: The Development and Validation of a New Tool for Spanish Adults.

Background: Cardiorespiratory fitness (CRF) is an important component of overall physical fitness and is associated with numerous health benefits, including a reduced risk of heart disease, diabetes, and obesity. However, direct measurement of CRF is time-consuming and therefore not feasible for screening purposes. Methods: A maximal treadmill exercise test with the Bruce protocol was performed to estimate VO2max in 1047 Spanish men and women aged 17 to 62 years. Weight, height, and heart rate were measured. Leisure-time physical activity (LTPA) was recorded using the Minnesota Leisure Time Physical Activity Questionnaire. A multiple linear regression model was developed to predict exercise-based VO2max. The validity of the model was examined by correlation, concordance, Bland-Altman analysis, cross-validation, and construct validity analysis. Results: There was no significant difference between VO2max obtained by the Bruce protocol (43.56 mL/kg/min) or predicted by the equation (43.59 mL/kg/min), with R2 of 0.57, and a standard error of the estimate of 7.59 mL/kg/min. Pearson's product-moment correlation and Lin's concordance correlation between measured and predicted CRF values were 0.75 and 0.72, respectively. Bland-Altman analysis revealed a significant proportional bias of non-exercise eCRF, overestimating unfit and underestimating highly fit individuals. However, 64.3% of participants were correctly classified into CRF tertile categories, with an important 69.9% in the unfit category. Conclusions: The eCRF equation was associated with several cardiovascular risk factors in the anticipated directions, indicating good construct validity. In conclusion, the non-exercise eCRF showed a reasonable validity to estimate true VO2max, and it may be a useful tool for screening CRF.

Genetic characteristics involved in COVID-19 severity. The CARGENCORS case-control study and meta-analysis.

Pre-existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID-19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID-19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID-19 severity. CARGENCORS (CARdiovascular GENetic risk score for Risk Stratification of patients positive for SARS-CoV-2 [COVID-19] virus) is an age- and sex-matched case-control study with 818 COVID-19 cases hospitalized with hypoxemia, and 1636 controls with COVID-19 treated at home. The association between severity and SNVs related to CAD (n = 32), inflammation (n = 19), thrombosis (n = 14), virus infectivity (n = 11), and two published to be related to COVID-19 severity was tested with adjusted logistic regression models. Two external independent cohorts were used for meta-analysis (SCOURGE and UK Biobank). After adjustment for potential confounders, 14 new SNVs were associated with COVID-19 severity in the CARGENCORS Study. These SNVs were related to CAD (n = 10), thrombosis (n = 2), and inflammation (n = 2). We also confirmed eight SNVs previously related to severe COVID-19 and virus infectivity. The meta-analysis showed five SNVs associated with severe COVID-19 in adjusted analyses (rs11385942, rs1561198, rs6632704, rs6629110, and rs12329760). We identified 14 novel SNVs and confirmed eight previously related to COVID-19 severity in the CARGENCORS data. In the meta-analysis, five SNVs were significantly associated to COVID-19 severity, one of them previously related to CAD.

Analysis of myocardial infarction incidence and case-fatality in the last three decades in the province of Girona.

INTRODUCTION AND OBJECTIVES: Myocardial infarction (MI) incidence and case fatality trends are highly informative but relatively untested at the population level. The objective of this work was to estimate MI incidence and case fatality in the Girona population aged 35-74 years, and to determine their 30-year trends (1990-2019). METHODS: The REGICOR (Girona Heart Registry) monitored MI incidence and case fatality rates from 1990 to 2008. For the period 2008 to 2019, we linked discharges from Girona hospitals (n=4 974 977) and mortality registry (n=70 405) during this period. Our linkage algorithm selected key MI diagnostic codes and removed duplicates. Estimates from the linkage algorithm and the REGICOR registry were compared using chi-square tests for overlapping years (2008-2009). We estimated the annual percent change (APC) of standardized MI incidence and 28-day case fatality, and analyzed their trends using joinpoint regression. RESULTS: MI incidence and case fatality estimates were similar in the linkage algorithm and the REGICOR registry. We observed significant decreasing trends in the incidence of MI. The trend was APC, -0.96% (95% confidence interval (95%CI), -1.4 to -0.53) in women from 1990 to 2019 and -4.2% (95%CI, -5.5 to -3.0) in men from 1994 to 2019. The largest decrease in case fatality was -3.8% (95%CI, -5.1 to -2.5) from 1995 to 2003 in women and -2.4% (95%CI, -2.9 to -1.9) from 1995 to 2004 in men, mainly due to prehospital case fatality declines: -1.8% (95%CI, -2.6 to -1.1) in men and -3.2% (95%CI, -4.6 to -1.8) in women. CONCLUSIONS: In Girona, MI incidence and case fatality decreased between 1990 and 2019. The incidence showed a slow but continuous decrease while case fatality only stabilized in the last decade, particularly in women.

Five-Year Changes in Inflammatory, Metabolic, and Oxidative Biomarkers and 10-Year Cardiovascular Disease Incidence: The REGICOR Cohort Study.

Ischemic cardiovascular diseases (CVD) originate from an imbalance between atherosclerotic plaque formation, instability, and endothelial healing dynamics. Our aim was to examine the relationship between 5-year changes in inflammatory, metabolic, and oxidative biomarkers and 10-year CVD incidence in a population without previous CVD. This was a prospective cohort study of individuals aged 35-74 years (n = 419) randomly selected from 5263 REGICOR participants without CVD recruited in 2005. Biomarkers were measured at baseline and in 2010. Participants were followed up until 2020 for a composite CVD endpoint including coronary artery disease, stroke, and peripheral artery disease. We used Cox regression to analyze the effect of biomarker levels on the occurrence of the composite endpoint, adjusted for traditional CVD risk factors and baseline levels of each biomarker. Individuals with elevated IL-6 or insulin after 5 years had a higher independent risk of CVD at 10 years, compared to those with lower levels. Each rise of 1 pg/mL of IL-6 or 10 pg/mL of insulin increased the 10-year risk of a CVD event by 32% and 2%, respectively. Compared to a model with traditional CVD risk factors only, the inclusion of IL-6 and insulin improved continuous reclassification by 51%. Elevated serum levels of IL-6 and insulin were associated with a higher risk of CVD at 10 years, independently of traditional CVD risk factors.

Cholesterol and Hypertension Treatment Improve Coronary Risk Prediction but Not Time-Dependent Covariates or Competing Risks.

Background and Aims: Cardiovascular (CV) risk functions are the recommended tool to identify high-risk individuals. However, their discrimination ability is not optimal. While the effect of biomarkers in CV risk prediction has been extensively studied, there are no data on CV risk functions including time-dependent covariates together with other variables. Our aim was to examine the effect of including time-dependent covariates, competing risks, and treatments in coronary risk prediction. Methods: Participants from the REGICOR population cohorts (North-Eastern Spain) aged 35-74 years without previous history of cardiovascular disease were included (n = 8470). Coronary and stroke events and mortality due to other CV causes or to cancer were recorded during follow-up (median = 12.6 years). A multi-state Markov model was constructed to include competing risks and time-dependent classical risk factors and treatments (2 measurements). This model was compared to Cox models with basal measurement of classical risk factors, treatments, or competing risks. Models were cross-validated and compared for discrimination (area under ROC curve), calibration (Hosmer-Lemeshow test), and reclassification (categorical net reclassification index). Results: Cancer mortality was the highest cumulative-incidence event. Adding cholesterol and hypertension treatment to classical risk factors improved discrimination of coronary events by 2% and reclassification by 7-9%. The inclusion of competing risks and/or 2 measurements of risk factors provided similar coronary event prediction, compared to a single measurement of risk factors. Conclusion: Coronary risk prediction improves when cholesterol and hypertension treatment are included in risk functions. Coronary risk prediction does not improve with 2 measurements of covariates or inclusion of competing risks.

Socioeconomic Status and Prognosis of Patients With ST-Elevation Myocardial Infarction Managed by the Emergency-Intervention "Codi IAM" Network.

Background: Despite the spread of ST-elevation myocardial infarction (STEMI) emergency intervention networks, inequalities in healthcare access still have a negative impact on cardiovascular prognosis. The Family Income Ratio of Barcelona (FIRB) is a socioeconomic status (SES) indicator that is annually calculated. Our aim was to evaluate whether SES had an effect on mortality and complications in patients managed by the "Codi IAM" network in Barcelona. Methods: This is a cohort study with 3,322 consecutive patients with STEMI treated in Barcelona from 2010 to 2016. Collected data include treatment delays, clinical and risk factor characteristics, and SES. The patients were assigned to three SES groups according to FIRB score. A logistic regression analysis was conducted to estimate the adjusted effect of SES on 30-day mortality, 30-day composite cardiovascular end point, and 1-year mortality. Results: The mean age of the patients was 65 ± 13% years, 25% were women, and 21% had diabetes mellitus. Patients with low SES were younger, more often hypertensive, diabetic, dyslipidemic (p < 0.003), had longer reperfusion delays (p < 0.03) compared to participants with higher SES. Low SES was not independently associated with 30-day mortality (OR: 0.95;9 5% CI: 0.7-1.3), 30-day cardiovascular composite end point (OR: 1.03; 95% CI: 0.84-1.26), or 1-year all-cause mortality (HR: 1.09; 95% CI: 0.76-1.56). Conclusion: Although the low-SES patients with STEMI in Barcelona city were younger, had worse clinical profiles, and had longer revascularization delays, their 30-day and 1-year outcomes were comparable to those of the higher-SES patients.

Standardized Comparison of Cardiovascular Risk Factors Prevalence in Spanish Women and Men Living with HIV and in the General Population.

People living with HIV (PLWH) have an increased risk of cardiovascular (CV) disease, likely due to a higher prevalence of CV risk factors. We compared the age-standardized prevalence and management of CV risk factors in PLWH to that of the general population in Spain. Blood pressure, lipid, glucose, and anthropometric profiles were cross-sectionally compared along with the treatment of hypertension, dyslipidemia, and diabetes in a general population cohort and a PLWH cohort. Prevalence rates were standardized by the direct method by 10-year age groups in European standard populations and stratified by gender. We included 47,593 individuals aged 35 to 74 years, 28,360 from the general population cohort and 19,233 from the PLWH cohort. Compared to the general population, PLWH had a higher concentration of triglycerides (>35 mg/dL in women and >26 mg/dL in men) and a higher prevalence of smoking (>23% and >17%) and diabetes (>9.9% and >8.5%). The prevalence of treated diabetes, hypertension, and dyslipidemia were up to three-fold lower in both women and men living with HIV. There was a significant difference in PLWH compared to the general population in the lipid, glucose, and anthropometric profile. In addition, PLWH were less often treated for diagnosed diabetes, hypertension, and dyslipidemia.

Estimated Population Prevalence of Heart Failure with Reduced Ejection Fraction in Spain, According to DAPA-HF Study Criteria.

Heart failure (HF) is one of the main causes of morbidity, mortality, and high healthcare costs. Dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, reduced cardiovascular mortality and hospitalization for HF compared to placebo in patients with chronic HF, and reduced ejection fraction (EF) in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study. Our aim was to estimate the number of patients with DAPA-HF characteristics in Spain. Our literature review identified epidemiological studies whose objective was to quantify the prevalence of HF and its comorbidities in Spain. We estimated the prevalence of HF with reduced EF, of New York Heart Association (NYHA) functional class II-IV, and with a glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m². In this population, we analysed the prevalence of diabetes using data from the REDINSCOR (Spanish Network for Heart Failure) registry. Our estimations indicate there are 594,684 patients ≥45 years old with HF in Spain (2.6% of this population age group), of which 52.4%, 84.0%, and 93.9% have reduced EF, are NYHA II-IV, and have a GFR ≥ 30 mL/min/1.73 m², respectively. By our calculations, approximately 245,789 Spanish patients would meet the DAPA-HF patient profile, and therefore could benefit from the protective cardiovascular effects of dapagliflozin.

Association of Circulating microRNAs with Coronary Artery Disease and Usefulness for Reclassification of Healthy Individuals: The REGICOR Study.

Risk prediction tools cannot identify most individuals at high coronary artery disease (CAD) risk. Oxidized low-density lipoproteins (oxLDLs) and microRNAs are actively involved in atherosclerosis. Our aim was to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive capacity of future CAD events. Human endothelial and vascular smooth muscle cells were treated with oxidized/native low-density lipoproteins, and microRNA expression was analyzed. Differentially expressed and CAD-related miRNAs were examined in serum samples from (1) a case-control study with 476 myocardial infarction (MI) patients and 487 controls, and (2) a case-cohort study with 105 incident CAD cases and 455 randomly-selected cohort participants. MicroRNA expression was analyzed with custom OpenArray plates, log rank tests and Cox regression models. Twenty-one microRNAs, two previously undescribed (hsa-miR-193b-5p and hsa-miR-1229-5p), were up- or down-regulated upon cell treatment with oxLDLs. One of the 21, hsa-miR-122-5p, was also upregulated in MI cases (fold change = 4.85). Of the 28 CAD-related microRNAs tested, 11 were upregulated in MI cases -1 previously undescribed (hsa-miR-16-5p)-, and 1/11 was also associated with CAD incidence (adjusted hazard ratio = 0.55 (0.35-0.88)) and improved CAD risk reclassification, hsa-miR-143-3p. We identified 2 novel microRNAs modulated by oxLDLs in endothelial cells, 1 novel microRNA upregulated in AMI cases compared to controls, and one circulating microRNA that improved CAD risk classification.