Prediction of individual lifetime cardiovascular risk and potential treatment benefit: development and recalibration of the LIFE-CVD2 model to four European risk regions.

AIMS: The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals. METHODS AND RESULTS: The updated LIFE-CVD (i.e. LIFE-CVD2) models were derived using individual participant data from 44 cohorts in 13 countries (687 135 individuals without established CVD, 30 939 CVD events in median 10.7 years of follow-up). LIFE-CVD2 uses sex-specific functions to estimate the lifetime risk of fatal and non-fatal CVD events with adjustment for the competing risk of non-CVD death and is systematically recalibrated to four distinct European risk regions. The updated models showed good discrimination in external validation among 1 657 707 individuals (61 311 CVD events) from eight additional European cohorts in seven countries, with a pooled C-index of 0.795 (95% confidence interval 0.767-0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (Clinical Practice Research Datalink) and the Netherlands (Extramural LUMC Academic Network). When using LIFE-CVD2 to estimate potential gain in CVD-free life expectancy from preventive therapy, projections varied by risk region reflecting important regional differences in absolute lifetime risk. For example, a 50-year-old smoking woman with a systolic blood pressure (SBP) of 140 mmHg was estimated to gain 0.9 years in the low-risk region vs. 1.6 years in the very high-risk region from lifelong 10 mmHg SBP reduction. The benefit of smoking cessation for this individual ranged from 3.6 years in the low-risk region to 4.8 years in the very high-risk region. CONCLUSION: By taking into account geographical differences in CVD incidence using contemporary representative data sources, the recalibrated LIFE-CVD2 model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making for cardiovascular prevention as recommended by 2021 European guidelines.

The study introduces LIFE-CVD2, a new tool that helps predict the risk of heart disease over a person's lifetime, and highlights how where you live in Europe can affect this risk.Using health information from over 687 000 people, LIFE-CVD2 looks at things like blood pressure and whether someone smokes to figure out their chance of having heart problems later in life. Health information from another 1.6 million people in seven different European countries was used to show that it did a good job of predicting who might develop heart disease.Knowing your heart disease risk over your whole life helps doctors give you the best advice to keep your heart healthy. Let us say there is a 50-year-old woman who smokes and has a bit high blood pressure. Right now, she might not look like she is in danger. But with the LIFE-CVD2 tool, doctors can show her how making changes today, like lowering her blood pressure or stopping smoking, could mean many more years without heart problems. These healthy changes can make a big difference over many years.

Cardiovascular Risk Factors Associated With Venous Thromboembolism.

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures: A panel of several established cardiovascular risk factors. Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

Prognostic models for locally advanced cervical cancer: external validation of the published models.

OBJECTIVE: To externally validate the prognostic models for predicting the time-dependent outcome in patients with locally advanced cervical cancer (LACC) who were treated with concurrent chemoradiotherapy in an independent cohort. METHODS: A historical cohort of 297 women with LACC who were treated with radical concurrent chemoradiotherapy from 1999 to 2014 at the 12 de Octubre University Hospital (H12O), Madrid, Spain. The external validity of prognostic models was quantified regarding discrimination, calibration, measures of overall performance, and decision curve analyses. RESULTS: The review identified 8 studies containing 13 prognostic models. Different (International Federation of Gynecology and Obstetrics [FIGO] stages, parametrium involvement, hydronephrosis, location of positive nodes, and race) but related cohorts with validation cohort (5-year overall survival [OS]=70%; 5-year disease-free survival [DFS]=64%; average age of 50; and over 79% squamous cell) were evaluated. The following models exhibited good external validity in terms of discrimination and calibration but limited clinical utility: the OS model at 3 year from Kidd et al.'s study (area under the receiver operating characteristic curve [AUROC]=0.69; threshold of clinical utility [TCU] between 36% and 50%), the models of DFS at 1 year from Kidd et al.'s study (AUROC=0.64; TCU between 24% and 32%) and 2 years from Rose et al.'s study (AUROC=0.70; TCU between 19% and 58%) and the distant recurrence model at 5 years from Kang et al.'s study (AUROC=0.67; TCU between 12% and 36%). CONCLUSION: The external validation revealed the statistical and clinical usefulness of 4 prognostic models published in the literature.

Risk of Cause-Specific Death in Individuals With Diabetes: A Competing Risks Analysis.

OBJECTIVE: Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death. RESEARCH DESIGN AND METHODS: We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths. RESULTS: We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes. CONCLUSIONS: Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes.

Early enteral nutrition in patients with hemodynamic failure following cardiac surgery.

BACKGROUND: Enteral nutrition (EN) is controversial in patients with circulatory compromise. This study assesses the feasibility and safety of EN given early after cardiac surgery in patients with hemodynamic failure. METHODS: Prospective observational study conducted in a surgical intensive care unit (ICU) of a tertiary hospital over 17 months. INCLUSION CRITERIA: Cardiac surgery patients with hemodynamic failure (dependence on 2 or more vasoactive drugs and/or mechanical circulatory support) requiring more than 24 hours of mechanical ventilation. Variables Examined: Descriptive data, daily hemodynamic data, and variables related to the efficacy and safety of EN. EN was performed according to our EN protocol. RESULTS: Of 642 patients admitted to the ICU, 37 (5.8%) met the inclusion criteria. Of these, 11 (29.7%) required mechanical circulatory support, and 25 (68.0%) met the criteria for early multiorgan dysfunction. Mortality was 13.5%. Mean EN duration was 12.3 days (95% confidence interval [CI], 9.6-15.0). The mean EN diet volume delivered/patient/d was 1199 mL (95% CI, 1118.7-1278.8), and mean EN energy delivered/patient/d was 1228.4 kcal (95% CI, 1145.8-1311). The set energy target was achieved in 15 patients (40.4%). The most common EN-related complication was constipation. No case of mesenteric ischemia was detected. CONCLUSIONS: Our findings indicate that early EN is feasible in this type of patients and not associated with serious complications. However, it is difficult to attain an appropriate energy target by EN alone. These observations point to a need for monitoring of daily energy delivery and balance, as well as careful monitoring of warning signs of intestinal ischemia.

Detection of adverse events in general surgery using the " Trigger Tool" methodology.

INTRODUCTION: Surgery is one of the high-risk areas for the occurrence of adverse events (AE). The purpose of this study is to know the percentage of hospitalisation-related AE that are detected by the «Global Trigger Tool¼ methodology in surgical patients, their characteristics and the tool validity. MATERIAL AND METHODS: Retrospective, observational study on patients admitted to a general surgery department, who underwent a surgical operation in a third level hospital during the year 2012. The identification of AE was carried out by patient record review using an adaptation of «Global Trigger Tool¼ methodology. Once an AE was identified, a harm category was assigned, including the grade in which the AE could have been avoided and its relation with the surgical procedure. RESULTS: The prevalence of AE was 36,8%. There were 0,5 AE per patient. 56,2% were deemed preventable. 69,3% were directly related to the surgical procedure. The tool had a sensitivity of 86% and a specificity of 93,6%. The positive predictive value was 89% and the negative predictive value 92%. CONCLUSIONS: Prevalence of AE is greater than the estimate of other studies. In most cases the AE detected were related to the surgical procedure and more than half were also preventable. The adapted «Global Trigger Tool¼ methodology has demonstrated to be highly effective and efficient for detecting AE in surgical patients, identifying all the serious AE with few false negative results.

Can partial nephrectomy preserve renal function and modify survival in comparison with radical nephrectomy?

OBJECTIVE: To investigate whether radical nephrectomy (RN) and nephron-sparing surgery (NSS) for T1 renal cell carcinoma influence renal function, oncological outcome or survival rate. MATERIAL AND METHODS: A retrospective study was performed, including 290 nephrectomies for tumours of a diameter of less than 7 cm; 174 radical nephrectomies were compared to 116 nephron-sparing surgeries. Preoperative and pathological data were compared between the two groups. The glomerular filtration rate was estimated using the abbreviated Modification of Diet and Renal Disease (MDRD4) study equation. The evolution of renal function was analysed from 6 months to 4 years after surgery, and the oncological outcomes were evaluated by means of cancer and non-cancer survival curves. RESULTS: The results showed a major impairment in renal function in the RN group compared to those who underwent NSS (25 vs 7 ml/min/1.73 m², 6 months after surgery), a difference that was maintained over time. Moreover, patients undergoing RN had a greater chance of developing renal failure. Overall, the survival curves showed a higher mortality rate for the RN group (p = 0.034), although the cancer-specific mortality rate did not show any statistically significant differences (p = 0.079). CONCLUSIONS: For stage T1 renal cortical tumours, NSS should, whenever possible, be regarded as the primary therapeutic option, given that it obtains similar oncological outcomes to RN and preserves renal function, which seems to translate into a lower overall mortality rate.

[1991-2004 follow-up of a Spanish general population cohort. Mortality and raising risk factors in the DRECE III Study (Diet and Risk of Cardiovascular Diseases in Spain)]. / Seguimiento de 1991 a 2004 de la mortalidad y los factores de riesgo emergentes en una cohorte de población general española. Estudio Drece III (Dieta y Riesgo de Enfermedades Cardiovasculares en España).

BACKGROUND: The DRECE III study is based on the follow up of a cohort representative of the Spanish general population. The mortality, its main causes and relevant risk factors have been analyzed. METHODS: The DRECE cohort is composed of 4783 subjects followed since 1991 to 2004 (70930 person-years). In 1991 a general medical exam including blood analysis and nutritional questionnaire was undertaken. Currently the age spam is from 18 to 73 years. Vital status and mortality causes were provided by the National Institute of Statistics. RESULTS: In this period, 125 deaths were registered: 53 persons (42.4%) due to cancer; 31 persons (24.8%) due to circulatory causes, of which 24 were due to cardiovascular origin. The remaining 41 (32.8%) deaths were included under the ICD 10 "Other chapters". For the all causes mortality the independent associated variables were: creatinina 1.5 mgr/dl, HR 3.78 (95% CI: 1.52-9.40); diabetes, HR 2.80 (95% CI: 1.74-4.46); male sex, HR 2.39 (I95% CI: 1.61-3.55); age, HR 1.08 (I95% CI: 1.07-1.10); and gammaglutamil transpeptidasa, HR 1.001 (I95% CI: 1.000-1.003). In the case of cancer mortality the risk factors founded were: age, HR 1.12 (I95% CI: 1.09-1.16); and tobacco, HR 1.33 (I95% CI: 1.14-1.54). For cardiovascular mortality were creatinina 1.5 mg/dl, HR 19.40 (I95% CI: 5.45-69.12); diabetes, HR 9.82 (I95% CI: 4.19-23.04); and age, HR 1.10 (I95% CI: 1.05-1.15). CONCLUSIONS: We obtain a mortality pattern where cancer is the most frequent cause. Classic risk factors appear associated to main death causes. Diabetes mellitus has an outstanding role as risk factor associated to early mortality. No specific diet data was associated neither to all causes mortality, nor to cardiovascular or cancer.

Previous tumour as a prognostic factor in stage I non-small cell lung cancer.

OBJECTIVE: To evaluate the effect of comorbidity as an independent prognostic factor in lung cancer. METHOD: Data on 2991 consecutive cases of lung cancer were collected prospectively from 19 Spanish hospitals between 1993 and 1997 by the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). To evaluate the effect of comorbidity on survival, 1121 patients with non-small cell lung cancer (NSCLC) in pathological stage I who underwent complete resection were selected, excluding operative mortality. The presence of specific comorbidities at the time of thoracotomy was registered prospectively. RESULTS: Cox regression analysis showed that tumour size (0-2, 2-4, 4-7, >7 cm) (HR 1.45 95% CI 1.08 to 1.95), 1.86 (95% CI 1.38 to 2.51), 2.84 (95% CI 1.98 to 4.08)), the presence of a previous tumour (HR 1.45 (95% CI 1.17 to 1.79)) and age (HR 1.02 (95% CI 1.01 to 1.03)) had a significant prognostic association with survival. This study excluded the presence of visceral pleural involvement or other comorbidities as independent variables. CONCLUSION: The presence of a previous tumour is an independent prognostic factor in pathological stage I NSCLC with complete resection, increasing the probability of death by 1.5 times at 5 years. It is independent of other comorbidities, TNM classification and age.

[Pulmonary hypertension during exercise in toxic oil syndrome]. / Hipertensión pulmonar con el ejercicio en el síndrome del aceite tóxico.

BACKGROUND AND OBJECTIVE: Toxic oil syndrome is a risk factor for pulmonary arterial hypertension (PAH) and new cases of this entity are emerging after more than 20 years since the initial toxic oil epidemic. Abnormal elevation of pulmonary systolic pressure with exercise may be considered an early marker of PAH in populations at risk. We aimed to analyze the pulmonary systolic pressure with exercise echocardiography in toxic oil syndrome patients. PATIENTS AND METHOD: 50 toxic oil syndrome patients (cases), and 20 healthy control subjects were submitted to rest and peak exercise echocardiography (semi supine cycloergometer) measuring pulmonary systolic pressure. In toxic oil syndrome patients, pulmonary carbon monoxide diffusion capacity was also analyzed. RESULTS: Peak exercise pulmonary systolic pressure was statistically similar in cases and controls. Nevertheless, 8% of cases reached a pulmonary systolic pressure > or = 80 mmHg and this fact was associated with mild pulmonary arterial hypertension, reduced right ventricular function and abnormal pulmonary diffusion capacity in the rest study. A rest pulmonary systolic pressure cut-off value > or = 27 mmHg had a 100% sensitivity and 71% specificity to predict a peak exercise systolic pulmonary pressure > or = 80 mmHg. CONCLUSIONS: A minority of toxic oil syndrome patients develop severe pulmonary arterial hypertension during exercise. This abnormal response is associated with other markers of pulmonary vasculopathy. Further studies are needed to elucidate the relation between these findings and the likelihood to develop pulmonary arterial hypertension in the future.

Heterogeneity of prognostic profiles in non-small cell lung cancer: too many variables but a few relevant.

OBJECTIVE: Many prognostic factors, exceeding 150, for non-small cell lung cancer (NSCLC) are mentioned in the literature. The different statistical weight of the some variables at issue, their heterogeneity and their clinical uselessness is reviewed. STUDY DESIGN AND SETTING: Survival analysis of a cohort of NSCLC operated (n = 1730, 1993-1997) was carried out utilizing different statistical approaches: Cox proportional hazard analysis (CPHA), logistic regression (LRA), and recursive partitioning (CART). RESULTS: CPHA identified 13 prognostic variables and 11 LRA. Of the 17 possible variables, 10 are coincident. CART provided five different diagnostic groups but only three differentiated survival levels. Parsimonious models were constructed including only T and N cancer staging variables. Areas under the ROC curve of 0.68 and 0.68 were found for CPHA and LGA parsimonious models respectively, and 0.72 and 0.71 for complete models. CONCLUSION: Variables with a minimal impact on the respective models and thus with little or scarce predictive clinical repercussion were identified. Differences in the prognostic profile of survival can be caused by the different methodological approaches used. No relevant differences were found between the parsimonious and complete models. Although the amount of information managed is considerable, there continues to be a large predictive gap yet to be explained.

[Prevalence of cardiovascular risk factors in a cohort of affected by the toxic oil syndrome]. / Prevalencia de factores de riesgo cardiovascular en una cohorte de afectados por el síndrome del aceite tóxico.

BACKGROUND AND OBJECTIVE: During the first stages of the toxic oil syndrome (TOS), elevations of the blood pressure as well as increases in the cholesterol, glucose and triglycerides levels were reported. Here we analyze these cardiovascular risk factors in the chronic phase of the illness and their distribution according to the severity of the illness. We also compare them with those found in the general population. PATIENTS AND METHOD: We studied a sample of 1,862 individuals aged between 35 and 65 years. A medical examination was performed in each and blood pressure, weight, height, tobacco consumption, cholesterol, glucose and triglycerides levels were measured. RESULTS: The prevalence of high blood pressure (>140/90 mmHg) was 46.1% and the prevalence of diabetes mellitus (>126 mg/dl) was 9.1%. The prevalence of obesity (BMI>30) was 24.9%. 11.8% of patients had hypertriglyceridemia (>200 mg/dl) and 19.8% had hypercholesterolemia (>250 mg/dl). 37.9% were smokers. The standardized prevalence rate (SPR) of high blood pressure was 1.35 (95% CI, 1.28-1.44); tobacco consumption SPR=1.27 (95% CI, 1.20-1.36); hypercholesterolemia SPR=1.10 (95% CI, 1.01-1.21). The prevalence of risk factors was higher among the most seriously affected subjects. CONCLUSIONS: The chronic phase of TOS is characterized by a high prevalence of cardiovascular risk factors, which was significantly higher than that expected in the general population.

Cardiovascular risk factors in 116 patients 5 years or more after liver transplantation.

We assessed the cardiovascular risk factors (CVRFs) in 116 stable liver transplant patients surviving for 5 years or more (median: 102 months). The prevalence of smokers was 29.3%, hypertension 49.1%, obesity 22.4%, hypercholesterolemia 34.5%, hypertriglyceridemia 11.2%, and hyperhomocysteinemia 57.8%. Diabetes was found in 21.5% of the patients, being more frequent in patients with hepatitis-C-virus infection (31.8% vs 15.3%; P=0.03). Patients on cyclosporine therapy had a higher prevalence of hypertension, hypercholesterolemia and hyperhomocysteinemia than those treated with tacrolimus. Multivariate analysis showed only an association between cyclosporine therapy and cholesterol concentrations (odds ratio:1.02; 95% confidence interval (CI): 1.00-1.03; P=0.01). The prevalence of hypertension, diabetes, hypercholesterolemia and hypertriglyceridemia was lower at the time of the study than at 1 and 3 years after transplantation ( P<0.05), probably related to steroid withdrawal. Comparing 87 patients' CVRFs with the general Spanish population, we found that the age-gender standardized prevalence ratio was not different: smoking 1.46 (95% CI: 0.88-1.76), obesity 1.16 (95% CI: 0.60-1.44), hypertension 1.55 (95% CI: 0.98-1.81), and hypercholesterolemia 0.64 (95%CI: 0.35-1.90). We conclude that the prevalence of CVRFs in liver transplant patients after 5 years or more is lower that found in the first years after the transplantation, and no different from that found within the Spanish population.

[Chronic Chlamydia pneumoniae infection in patients with coronary disease. Relation with increased fibrinogen values]. / Infección crónica por Chlamydia pneumoniae en pacientes con enfermedad coronaria. Relación con el incremento de los valores de fibrinógeno.

BACKGROUND: A number of studies have suggested that infection with Chlamydia pneumoniae can play a role in development of atherosclerosis. The goal of this study was to know the prevalence of chronic C. pneumoniae infection, evaluated with IgG antibodies seropositivity, in Spanish patients with coronary disease and its association with inflammatory markers and cardiovascular risk factors. PATIENTS AND METHOD: In 176 patients with coronary disease IgG and IgM antibodies to C. pneumoniae were determined by enzyme immunoassay. In addition, fibrinogen and C-reactive protein values were measured as inflammatory markers. Controls were 55 healthy subjects whose age was not different from patients. Seropositivity for C. pneumoniae was considered when indices of IgG and/or IgM antibodies were higher than mean plus two standard deviations of control values. Three patients with seropositivity for IgM were excluded. RESULTS: In 126 patients and 2 controls a seropositivity against C. pneumoniae was proved (72.8% vs 4.2%; p < 0.001). Cardiovascular risk factors were not different in seropositive and seronegative groups of patients. Prevalence of hyperfibrinogenemia was higher in the former group (38.8% vs 19.1%; p = 0.01). The number of the patients with increased values of C-reactive protein was similar in both groups, although these values could be modified by treatment with statins. In multivariate analysis an association between seropositivity for C. pneumoniae and hyperfibrinogenemia was found (odds ratio [OR] = 2.42; 95% confidence interval, 1.07-5.48; p = 0.03) after adjusting for age, gender, smoking, hypertension, hypercholesterolemia and diabetes. CONCLUSIONS: Chronic infection with C. pneumoniae in patients with coronary disease is very prevalent, and it is associated with increased fibrinogen values.