Nonfatal Cardiovascular Events Research Articles

Prognostic Value of Cardiovascular Biomarkers in the Population.

Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Association between Glucose-lowering Treatments and Risk of Diabetic Retinopathy in People with Type 2 Diabetes: A Nationwide Cohort Study.

Glycaemic variability is possibly linked to the development of diabetic retinopathy, and newer second-line glucose-lowering treatments in type 2 diabetes might reduce glycaemic variability. This study aimed to investigate whether newer second-line glucose-lowering treatments are associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes. A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income, history of late-diabetic complications, history of non-fatal major adverse cardiovascular events, history of chronic kidney disease, and history of hypoglycaemic episodes. Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin + glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium-glucose cotransporter-2 inhibitor (SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of diabetic retinopathy compared with all regimens investigated. Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second- line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However, many other considerations concerning the choice of second-line glucose-lowering treatment for type 2 diabetes patients should be taken into account.

Cardiovascular events after exacerbations of chronic obstructive pulmonary disease: Results from the EXAcerbations of COPD and their OutcomeS in CardioVascular diseases study in Italy

IntroductionExacerbations of chronic obstructive pulmonary disease (COPD) can increase the risk of severe cardiovascular events. ObjectiveAssess the crude incidence rates (IR) of cardiovascular events and the impact of exacerbations on the risk of cardiovascular events within different time periods following an exacerbation. MethodsCOPD patients aged ≥45 years between 01/01/2015 and 12/31/2018 were identified from the Fondazione Ricerca e Salute administrative database. IRs of severe non-fatal and fatal cardiovascular events were obtained for post-exacerbation time periods (1–7, 8–14, 15–30, 31–180, 181–365 days). Time-dependent Cox proportional hazard models compared cardiovascular risks between periods with and without exacerbations. ResultsOf 216,864 COPD patients, >55 % were male, mean age was 74 years, frequent comorbidities were cardiovascular, metabolic and psychiatric. During an average 34-month follow-up, 69,620 (32 %) patients had ≥1 exacerbation and 46,214 (21 %) experienced ≥1 cardiovascular event. During follow-up, 55,470 patients died; 4,661 were in-hospital cardiovascular-related deaths. Among 10,269 patients experiencing cardiovascular events within 365 days post-exacerbation, the IR was 15.8 per 100 person-years (95 %CI 15.5–16.1). Estimated hazard ratios (HR) for the cardiovascular event risk associated with periods post-exacerbation were highest within 7 days (HR: 34.3, 95 %CI: 33.1–35.6), especially for heart failure (HR 50.6; 95 %CI 48.6–52.7) and remained elevated throughout 365 days (HR 1.1, 95 %CI 1.02–1.13). ConclusionsCOPD patients in Italy are at high risk of severe cardiovascular events following exacerbations, suggesting the need to prevent exacerbations and possible subsequent cardiovascular events through early interventions and treatment optimization.

Insomnia and risk of mortality in older adults.

Existing evidence linking insomnia to all-cause mortality in older individuals remains inconclusive. We conducted a retrospective study of a large cohort of veterans aged 65-80 years old identified from the Corporate Data Warehouse, a large data repository derived from the Veterans Health Administration integrated medical records. Veterans' enrollees with and without International Classification of Diseases, Ninth and Tenth Revision, codes corresponding to insomnia diagnosis between 1 January 2010 and 30 March 2019 were assessed for eligibility. The primary outcome was all-cause mortality. A total of 36,269 veterans, 9584 with insomnia and 26,685 without insomnia, were included in the analysis. Baseline mean (SD) age was 72.6 (4.2) years. During a mean follow-up of 6.0 (2.9) years of the propensity score matched sample, the mortality rate was 34.8 [95% confidence interval: 33.2-36.6] deaths per 1000 person-years among patients with insomnia compared with 27.8 [95% confidence interval: 26.6-29.1] among patients without insomnia. In a Cox proportional hazards model, insomnia was significantly associated with higher mortality (hazard ratio: 1.39; [95% confidence interval: 1.27-1.52]). Patients with insomnia also had a higher risk of non-fatal cardiovascular events (hazard ratio: 1.21; [95% confidence interval: 1.06-1.37]). Secondary stratified analyses by sex, race, ethnicity and hypertension showed no evidence of effect modification. A higher risk of mortality (hazard ratio: 1.51; [95% confidence interval: 1.33-1.71]) was observed when depression was present compared with absent (hazard ratio: 1.26; [95% confidence interval: 1.12-1.44]; p = 0.02). In this cohort study, insomnia was associated with increased risk-adjusted mortality and non-fatal cardiovascular events in older individuals.

Phenotypic Expression and Outcomes in Patients with the p.Arg301Gln GLA Variant in Anderson-Fabry Disease.

The p.Arg301Gln variant in the α -galactosidase A gene (GLA) has been poorly described in the literature. The few reports show controversial information, with both classical and nonclassical Anderson-Fabry Disease (AFD) presentation patterns. The aim of this study was to analyze the penetrance, clinical phenotype, and biochemical profile of an international cohort of patients carrying the p.Arg301Gln genetic variant in the GLA gene. This was an observational, international, and retrospective cohort case series study of patients carrying the p.Arg301Gln variant in the GLA gene associated with AFD disease. Forty-nine p.Arg301Gln GLA carriers, 41% male, were analyzed. The penetrance was 63% in the entire cohort and 1.5 times higher in men. The mean age of symptoms onset was 41 years; compared to women, men presented symptoms earlier and with a shorter delay to diagnosis. The typical clinical triad-cornea verticillate, neuropathic pain, and angiokeratomas-affected only 20% of the cohort, with no differences between genders. During follow-up, almost 20% of the patients presented some type of nonfatal cardiovascular and renal event (stroke, need for dialysis, heart failure, and arrhythmias requiring intracardiac devices), predominantly affecting men. Residual levels were the most common finding of α-GAL A enzyme activity, only a few women had a normal level; a small proportion of men had undetectable levels. The incidence of combined outcomes including all causes of death was 33%, and the cumulative incidence of all-cause mortality was 9% at the follow-up. Patients carrying the p.Arg301Gln GLA variant have a high penetrance, with predominantly cardiorenal involvement and clinical onset of the disease in middle age. Only a small proportion showed the classic clinical presentation of AFD. As in other X-linked diseases, males were more affected by severe cardiovascular and renal events. This genotype-phenotype correlation could be useful from a practical clinical point of view and for future decision making.

Non-dipping blood pressure pattern is associated with cardiovascular events in a 21-year follow-up study.

Non-dipping blood pressure (BP) pattern is a predictor for cardiovascular (CV) events and mortality. We evaluated dipping status change and its association with incidence of non-fatal CV events in middle-aged subjects. The OPERA study was carried out during the years 1991-1993, with a follow-up study 21.7 years later. In this study, we included 452 participants with 24-h ambulatory BP measurements (ABPM) available in both surveys. The study population was divided into four groups according to the dipping pattern change: dipping-dipping (n = 152/33.6%), dipping-non-dipping (n = 198/43.8%), non-dipping-dipping (n = 20/4.4%), and non-dipping-non-dipping (n = 82/18.1%). Sixty-five participants experienced a CV event (14.4%) during the 21.7 (SD 0.8) years of follow-up. The incidence of events was highest (28%) in the non-dipping-non-dipping group, and lowest (6.6%) in the dipping-dipping group (p < 0.001). In Cox regression analyses the covariates were age, sex, total cholesterol, hypertension and use of antihypertensive medication, systolic office BP and ambulatory mean or nighttime systolic BP, as well as the change in the variables during the follow-up period. After adjustments, the association of the non-dipping-non-dipping pattern with CV events compared with the dipping-dipping pattern remained significant (HR 4.01; 95% CI 1.89-8.67, p < 0.001). In summary, non-dipping-non-dipping pattern was associated with non-fatal CV events in the long term, and the effect was independent of the conventional risk factors including office and ambulatory BP levels.

Cholesterol-Lowering Strategies for Cardiovascular Disease Prevention: The Importance of Intensive Treatment and the Simplification of Medical Therapy.

Cardiovascular diseases (CVDs) are a leading global cause of mortality and are primarily driven by atherosclerotic coronary artery disease. Their pathogenesis involves multi-factorial mechanisms, among which low-density lipoprotein (LDL) plays a causative role. Recent ESC/EAS guidelines advocate for a shift toward new risk estimation algorithms that better emphasize non-fatal cardiovascular events, lifetime risk prediction, and tailored pharmacological approaches, including statin + ezetimibe and triple therapy, in specific cases. Intensive lipid-lowering therapy has been shown to be pivotal, especially in post-acute coronary events. Intracoronary imaging has revealed insights into the composition of plaque and demonstrated the significant regression that can be achieved through the use of statins such as rosuvastatin and atorvastatin. The positive effects of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, particularly alirocumab and evolocumab, on plaque regression, have been demonstrated. Inclisiran, which targets PCSK9 gene expression, significantly reduces LDL cholesterol. The associated challenges include hesitancy to prescribe intensive regimens and limited treatment adherence, highlighting the need for pharmacological combinations to improve therapeutic outcomes.

Mortality and Cardiovascular End Points In Relation to the Aortic Pulse Wave Components: An Individual-Participant Meta-Analysis.

Wave separation analysis enables individualized evaluation of the aortic pulse wave components. Previous studies focused on the pressure height with overall positive but differing results. In the present analysis, we assessed the associations of the pressure of forward and backward (Pfor and Pref) pulse waves with prospective cardiovascular end points, with extended analysis for time to pressure peak (Tfor and Tref). Participants in 3 IDCARS (International Database of Central Arterial Properties for Risk Stratification) cohorts (Argentina, Belgium, and Finland) aged ≥20 years with valid pulse wave analysis and follow-up data were included. Pulse wave analysis was done using the SphygmoCor device, and pulse wave separation was done using the triangular method. The primary end points consisted of cardiovascular mortality and nonfatal cardiovascular and cerebrovascular events. Multivariable-adjusted Cox regression was used to calculate hazard ratios. A total of 2206 participants (mean age, 57.0 years; 55.0% women) were analyzed. Mean±SDs for Pfor, Pref, Tfor, and Tfor/Tref were 31.0±9.1 mm Hg, 20.8±8.4 mm Hg, 130.8±35.5 ms, and 0.51±0.11 ms, respectively. Over a median follow-up of 4.4 years, 146 (6.6%) participants experienced a primary end point. Every 1 SD increment in Pfor, Tfor, and Tfor/Tref was associated with 27% (95% CI, 1.07-1.49), 25% (95% CI, 1.07-1.45), and 32% (95% CI, 1.12-1.56) higher risk, respectively. Adding Tfor and Tfor/Tref to existing risk models improved model prediction (∆Uno's C, 0.020; P<0.01). Pulse wave components were predictive of composite cardiovascular end points, with Tfor/Tref showing significant improvement in risk prediction. Pending further confirmation, the ratio of time to forward and backward pressure peak may be useful to evaluate increased afterload and signify increased cardiovascular risk.

Impacts of Febuxostat on Cerebral and Cardiovascular Events in Elderly Patients with Hyperuricemia: Post Hoc Analysis of a Randomized Controlled Trial.

A recent meta-analysis found no benefit of uric acid-lowering therapy including febuxostat on death, cardiovascular events, or renal impairment. However, there may be populations that benefit from febuxostat in reducing mortality and cerebral and cardiovascular events. The aim of the present study was to examine the clinical benefit of febuxostat in elderly patients stratified by age using Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy (FREED) data. FREED was a randomized study involving patients aged 65 years or older with hyperuricemia and risk factors for cerebral, cardiovascular, or renal diseases. A total of 1,070 patients were included in this post hoc analysis, divided into 2 age groups: 65-74 years and ≥ 75 years. Patients were randomized into febuxostat and non-febuxostat groups, with uric acid levels monitored for 36 months. The primary composite end point included cerebral, cardiovascular, and renal events. In patients aged between 65 and 74 years, febuxostat significantly reduced the risk of future cerebral and cardiorenovascular events. However, no effects of febuxostat were found in the older population aged ≥ 75 years. Heterogeneity in potential interactions between the age and febuxostat treatment was particularly observed in non-fatal cerebral and cardiovascular events and all-cause death. Patients aged ≥ 75 years exhibited more pre-existing factors associated with cerebral and cardiorenovascular events than those aged 65-74 years. The effectiveness of febuxostat varies by age group, with potential benefits for patients aged 65-74 years. The effects of febuxostat are complex and it is important to consider patient characteristics in its clinical use.

Pentraxin-3 and Outcomes in CKD: A Systematic Review and Meta-analysis

Rationale & ObjectiveLong pentraxin-3 (PTX-3) serves as a biomarker for prognosticating adverse clinical outcomes in individuals with chronic kidney disease (CKD). The objective of the current meta-analysis was to evaluate the prognostic efficacy of PTX-3 in patients with CKD. Additionally, we compared the prognostic effectiveness of PTX-3 and the short pentraxin C-reactive protein (CRP) in the identical cohort of CKD patients. Study DesignSystematic review and meta-analysis. Setting & ParticipantsCKD patients with or without dialysis. Selection Criteria for StudiesA cohort study with a minimum 1-year follow-up. Data ExtractionRisk measurements, adjusted hazard risk (HR) with 95% confidence interval (CI), and modified variables. Analytical ApproachTo aggregate the adjusted effect estimates, a fixed-effects or random-effects model was employed. ResultsNine studies covering 1825 CKD patients were selected in the present paper. Six of the 9 studies exclusively included hemodialysis patients. The collected findings indicated that CKD patients in the highest tertile of PTX-3 demonstrated significantly higher risks of all-cause mortality (HR 1.92, 95% CI 1.44-2.56), cardiovascular death (HR 1.98, 95% CI 1.28-3.05), infectious death (HR 5.26, 95% CI 1.60-17.31), and fatal and non-fatal cardiovascular events (HR 1.81, 95% CI 1.35-2.42), as compared to those in the lowest tertile. These significant associations with risk were also observed when effect estimates were presented as per unit change in PTX-3. Moreover, when comparing the prognostic value of PTX-3 and CRP in the same individuals (5 studies covering 904 patients), PTX-3 proved to be a satisfactory predictor of adverse events in these patients, while CRP failed to exhibit such predictive capability, regardless of the type of effect estimate used. LimitationsA relatively small sample size and some heterogeneity. ConclusionsPentraxin 3 is associated with adverse events in individuals with CKD and may be a more reliable predictor of adverse clinical events than CRP in this population.

Hypoglycemia and Cardiovascular Outcomes in the CARMELINA and CAROLINA Trials of Linagliptin

Previous studies have reported an association between hypoglycemia and cardiovascular (CV) events in people with type 2 diabetes (T2D), but it is unclear if this association is causal or identifies a high-risk patient phenotype. To evaluate the associations between hypoglycemia and CV outcomes. This secondary analysis was a post hoc assessment of the multinational, double-blind CARMELINA (Cardiovascular and Renal Microvascular Outcome Study With Linagliptin; 2013-2016) and CAROLINA (Cardiovascular Outcome Trial of Linagliptin vs Glimepiride in Type 2 Diabetes; 2010-2018) randomized clinical trials of the antihyperglycemic drug, linagliptin, a dipeptidyl peptidase 4 inhibitor. Participants were adults with T2D at high CV risk with or without high kidney risk. By design, participants in the CARMELINA trial had longer duration of T2D and had a higher CV risk than participants in the CAROLINA trial. Data analyses were conducted between June 2021 and June 2023. Linagliptin or placebo in the CARMELINA trial, and linagliptin or glimepiride in the CAROLINA trial. The primary outcome for both trials was CV death, myocardial infarction (MI), or stroke (3-point major adverse CV events [3P-MACE]). For the present analyses, hospitalization for heart failure (HF) was added. Hypoglycemia was defined as plasma glucose less than 54 mg/dL or severe hypoglycemia (episodes requiring the assistance of another person). Associations between the first hypoglycemic episode and subsequent CV events and between nonfatal CV events (MI, stroke, hospitalization for HF) and subsequent hypoglycemic episodes were assessed using multivariable Cox proportional hazards regression models. Sensitivity analyses explored the risk of CV events within 60 days after each hypoglycemic episode. In the CARMELINA trial (6979 patients; 4390 males [62.9%]; mean [SD] age, 65.9 [9.1] years), there was an association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (hazard ratio [HR], 1.23; 95% CI, 1.04-1.46) as well as between nonfatal CV events and subsequent hypoglycemia (HR, 1.39; 95% CI, 1.06-1.83). In the CAROLINA trial (6033 patients; 3619 males (60.0%); mean [SD] age, 64.0 [9.5] years), there was no association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (HR, 1.00; 95% CI, 0.76-1.32) and between nonfatal CV events and subsequent hypoglycemia (HR, 1.44; 95% CI, 0.96-2.16). In analyses of CV events occurring within 60 days after hypoglycemia, there was either no association or too few events to analyze. This study found bidirectional associations between hypoglycemia and CV outcomes in the CARMELINA trial but no associations in either direction in the CAROLINA trial, challenging the notion that hypoglycemia causes adverse CV events. The findings from the CARMELINA trial suggest that both hypoglycemia and CV events more likely identify patients at high risk for both. ClinicalTrials.gov Identifier: NCT01897532 (CARMELINA) and NCT01243424 (CAROLINA).

Validation of the IberScore model in a primary care population

BackgroundThis study aimed to validate the IberScore cardiovascular risk model in a population attended in the primary care setting. MethodsA cohort of patients with no history of cardiovascular disease visited in a primary care center during the years 2008 and/or 2009 and followed up until 2018 was selected.Cardiovascular risk was calculated with the IberScore formula for all the subjects of the cohort and the model was calibrated, graphically represented by risk deciles the proportion of expected events and proportion of observed events at 10-year follow-up, stratified by sex. The area under the ROC curve was calculated to assess the discrimination of the model. ResultsA total of 10,085 patients visited during the years 2008 and/or 2009 were included in the study. Men showed a mean 10-year risk of suffering a fatal or non-fatal cardiovascular events according to IberScore of 17.07% (SD 20.13), with a mean estimated vascular age of more than 4 years higher than the biological age; while women had a mean 10-year risk of 7.91% (SD 9.03), with an estimated vascular age of more than 2 years above the biological age.The area under the ROC curve showed a discrimination index of the model of 0.86 (95% CI 0.84–0.88) in men and 0.82 (95% CI 0.79–0.85) in women. ConclusionIberScore model discriminates well in the population attended in primary care but the model overestimates the risk.

Role of High-sensitivity C-reactive Protein in Future Cardiovascular Events in Hemodialysis Patients.

The pathogenesis of cardio-vascular disease (CVD) in hemodialysis (HD) patients involves inflammation and oxidative stress. High-sensitivity C-reactive protein (hs-CRP) is an established inflammatory biomarker associated with CVD. Several studies have suggested that the inflammatory biomarker pentraxin-3 (PTX-3) and the oxidative stress-related biomarker soluble lectin-like low-density lipoprotein receptor-1 (sLOX-1) are novel biomarkers for CVD in non-HD populations. This study aimed to clarify the association of these established and novel biomarkers with future cardiovascular (CV) events in HD patients. This was a single-center prospective cohort study that included 255 HD patients. The primary outcome was the composite of nonfatal and fatal CV events. The event-free survival rate between the two groups according to the median plasma level of each biomarker at baseline was evaluated using the Kaplan-Meier method. The risk for CV events at elevated levels of each biomarker was estimated using Cox proportional hazard model. We observed 44 CV events during the median follow-up period of 743 days. The event-free survival rate significantly differed between the two groups in hs-CRP but not in PTX-3 or sLOX-1. The unadjusted hazard ratio (HR) for CV events in patients with hs-CRP levels above the median was 2.63 [95% confidence interval (CI)=1.37-5.02]. The HR remained significant after adjusting for age, sex, history of CVD, and diabetes (HR=2.30; 95%CI=1.20-4.43). In HD patients, hs-CRP may have a predictable role for future CV events, whereas PTX-3 and sLOX-1 do not.

Impact of preeclampsia and parity on sex-based discrepancies in subclinical carotid atherosclerosis in type 1 diabetes.

The excess risk of fatal and non-fatal cardiovascular events is roughly twice as high in women than in men with type 1 diabetes (T1D). To evaluate the impact of preeclampsia and parity on sex-based discrepancies in preclinical atherosclerosis and on the diagnostic performance of a cardiovascular risk scale. Cross-sectional study. Single tertiary hospital. 728 T1D (48.5% women) without cardiovascular disease and age ≥40 years, nephropathy, and/or ≥10 years of diabetes duration with another risk factor. Standardized carotid ultrasonography. Carotid plaque determined by ultrasonography and cardiovascular risk estimated according to the Steno T1 Risk Engine (Steno-Risk). Nulliparous women and parous women without previous preeclampsia had a lower risk for carotid plaque than men (adjusted odds ratio [OR]: 0.48, 95% confidence interval [0.28-0.82]; adjusted OR: 0.51 [0.33-0.79], respectively), without differences in the preeclampsia group. The prevalence of carotid plaque increased as the estimated cardiovascular risk increased in all subgroups except for preeclampsia group. The area under the curve (AUC) of the Steno-Risk for identifying ≥2 carotid plaques was lower in the preeclampsia group (men: 0.7886, nulliparous women: 0.9026, women without preeclampsia: 0.8230, preeclampsia group: 0.7841; p between groups=0.042). Neither the addition of parity nor preeclampsia in the Steno-Risk led to a statistically significant increase in the AUC. The risk for carotid plaque in women compared to men decreased as exposure to obstetric factors diminished. However, the addition of these factors did not improve the prediction of the Steno-Risk.

Temporal Risk of Nonfatal Cardiovascular Events After Chronic Obstructive Pulmonary Disease Exacerbation: A Population-based Study.

Rationale: Cardiovascular events after chronic obstructive pulmonary disease (COPD) exacerbations are recognized. Studies to date have been post hoc analyses of trials, did not differentiate exacerbation severity, included death in the cardiovascular outcome, or had insufficient power to explore individual outcomes temporally.Objectives: We explore temporal relationships between moderate and severe exacerbations and incident, nonfatal hospitalized cardiovascular events in a primary care-derived COPD cohort.Methods: We included people with COPD in England from 2014 to 2020, from the Clinical Practice Research Datalink Aurum primary care database. The index date was the date of first COPD exacerbation or, for those without exacerbations, date upon eligibility. We determined composite and individual cardiovascular events (acute coronary syndrome, arrhythmia, heart failure, ischemic stroke, and pulmonary hypertension) from linked hospital data. Adjusted Cox regression models were used to estimate average and time-stratified adjusted hazard ratios (aHRs).Measurements and Main Results: Among 213,466 patients, 146,448 (68.6%) had any exacerbation; 119,124 (55.8%) had moderate exacerbations, and 27,324 (12.8%) had severe exacerbations. A total of 40,773 cardiovascular events were recorded. There was an immediate period of cardiovascular relative rate after any exacerbation (1-14 d; aHR, 3.19 [95% confidence interval (CI), 2.71-3.76]), followed by progressively declining yet maintained effects, elevated after one year (aHR, 1.84 [95% CI, 1.78-1.91]). Hazard ratios were highest 1-14 days after severe exacerbations (aHR, 14.5 [95% CI, 12.2-17.3]) but highest 14-30 days after moderate exacerbations (aHR, 1.94 [95% CI, 1.63-2.31]). Cardiovascular outcomes with the greatest two-week effects after a severe exacerbation were arrhythmia (aHR, 12.7 [95% CI, 10.3-15.7]) and heart failure (aHR, 8.31 [95% CI, 6.79-10.2]).Conclusions: Cardiovascular events after moderate COPD exacerbations occur slightly later than after severe exacerbations; heightened relative rates remain beyond one year irrespective of severity. The period immediately after an exacerbation presents a critical opportunity for clinical intervention and treatment optimization to prevent future cardiovascular events.

Derivation and Internal Validation of a Disease-Specific Cardiovascular Risk Prediction Model for Patients With Psoriatic Arthritis and Psoriasis.

To address suboptimal cardiovascular risk prediction in patients with psoriatic disease (PsD), we developed and internally validated a five-year disease-specific cardiovascular risk prediction model. We analyzed data from a prospective cohort of participants with PsD without a history of cardiovascular events. Traditional cardiovascular risk factors and PsD-related measures of disease activity were considered as potential predictors. The study outcome included nonfatal and fatal cardiovascular events. A base prediction model included 10 traditional cardiovascular risk factors. Eight PsD-related factors were assessed by adding them to the base model to create expanded models, which were controlled for PsD therapies. Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression with 10-fold cross-validation. Model performance was assessed using measures of discrimination and calibration and measures of sensitivity and specificity. Between 1992 and 2020, 85 of 1,336 participants developed cardiovascular events. Discrimination of the base model (with traditional cardiovascular risk factors alone) was excellent, with an area under the receiver operator characteristic curve (AUC) of 85.5 (95% confidence interval [CI] 81.9-89.1). Optimal models did not select any of the tested disease-specific factors. In a sensitivity analysis, which excluded lipid lowering and antihypertensive treatments, the number of damaged joints was selected in the expanded model. However, this model did not improve risk discrimination compared to the base model (AUC 85.5, 95% CI 82.0-89.1). Traditional cardiovascular risk factors alone are effective in predicting cardiovascular risk in patients with PsD. A risk score based on these factors performed well, indicating excellent discrimination and calibration.

Primary hyperaldosteronism: the choice in favor of conservative surgery

Primary hyperaldosteronism (PHA) is the most common cause of secondary arterial hypertension among endocrine disorders.  Given that patients with this pathology are at a higher risk of developing fatal and non-fatal cardiovascular events, early  diagnosis and timely treatment are of great importance. Currently, the two main forms of PHA are aldosterone-producing  adenoma and bilateral adrenal hyperplasia, which are treated with laparoscopic adrenalectomy or pharmacotherapy with  mineralocorticoid receptor antagonists. Although most patients experience restoration of their functional and metabolic  status after surgical intervention, some may develop postoperative adrenal insuffi ciency, which requires long-term hormone  replacement therapy. This review examines the options for organ-preserving surgeries, such as partial adrenalectomy and  selective embolization of the adrenal artery.

Risk of cardiovascular events after an exacerbation of chronic obstructive pulmonary disease: results from the EXACOS-CV cohort study using the PHARMO Data Network in the Netherlands

BackgroundPeople living with chronic obstructive pulmonary disease (COPD) have an increased risk of experiencing cardiovascular (CV) events, particularly after an exacerbation. Such CV burden is not yet known for incident COPD patients. We examined the risk of severe CV events in incident COPD patients in periods following either moderate and/or severe exacerbations.MethodsPersons aged ≥ 40 years with an incident COPD diagnosis from the PHARMO Data Network were included. Exposed time periods included 1–7, 8–14, 15–30, 31–180 and 181–365 days following an exacerbation. Moderate exacerbations were defined as those managed in outpatient settings; severe exacerbations as those requiring hospitalisation. The outcome was a composite of time to first severe CV event (acute coronary syndrome, heart failure decompensation, cerebral ischaemia, or arrhythmia) or death. Hazard ratios (HR) were estimated for association between each exposed period and outcome.Results8020 patients with newly diagnosed COPD were identified. 2234 patients (28%) had ≥ 1 exacerbation, 631 patients (8%) had a non-fatal CV event, and 461 patients (5%) died during a median follow-up of 36 months. The risk of experiencing the composite outcome was increased following a moderate/severe exacerbation as compared to time periods of stable disease [range of HR: from 15.3 (95% confidence interval 11.8–20.0) in days 1–7 to 1.3 (1.0–1.8) in days 181–365]. After a moderate exacerbation, the risk was increased over the first 180 days [HR 2.5 (1.3–4.8) in days 1–7 to 1.6 (1.3–2.1) in days 31–180]. After a severe exacerbation, the risk increased substantially and remained higher over the year following the exacerbation [HR 48.6 (36.9–64.0) in days 1–7 down to 1.6 (1.0–2.6) in days 181–365]. Increase in risk concerned all categories of severe CV events.ConclusionsAmong incident COPD patients, we observed a substantial risk increase of severe CV events or all-cause death following either a moderate or severe exacerbation of COPD. Increase in risk was highest in the initial period following an exacerbation. These findings highlight the significant cardiopulmonary burden among people living with COPD even with a new diagnosis.

Early screening for metabolic syndrome opens a window of opportunity - learnings from a long-term, population-based study

Abstract Introduction The metabolic syndrome (MetS) represents a cluster of risk factors that predict cardiovascular disease (CVD) and type 2 diabetes. Early detection of MetS opens up for a successful treatment of the cardiovascular (CV) risk factors involved, hopefully leading to later advent of CVD in the general population. Purpose In this long-term, population-based study we aimed to investigate how presence of MetS, in middle-aged men and women, was associated with all-cause mortality and non-fatal CVD later in life. Methods Between 1990 -1999 a screening program was conducted among 40- and 50-year-old inhabitants in the County of Västmanland, Sweden. Data on lifestyle habits and socio-economic status were collected. Total cholesterol, fasting blood glucose, blood pressure, weight, height, waist and hip circumference were measured. Individuals that met three or more of the following risk factors were classified with MetS: waist circumference: ≥102 cm (men) and ≥88 cm (women), total cholesterol: ≥6.1 mmol/ l, blood pressure: ≥130 and/ or ≥85 mm Hg (or previous diagnosis of hypertension) or fasting plasma glucose: ≥5.6 mmol/ l (or previous diagnosis of type 2 diabetes). A control group was identified with individuals from the same population, without MetS diagnosis. Each participant with MetS was matched to two controls regarding sex, age and date for the health examination. The association between midlife MetS and all-cause mortality and non-fatal CV events (stroke and myocardial infarction) was adjusted for age, sex, smoking, physical inactivity, educational level, BMI, hip circumference and living alone or with family members. Multivariable cox regression and Kaplan-Meier analyses were used. Results A total number of 5084 individuals met the criteria for MetS and a control group of 10 168 individuals was identified. The median (Q1, Q3) follow-up time was 27 years (24.6, 30.1), corresponding to 130 820 and 269 696 person-years at risk in the MetS and the control group respectively. During follow up, 1317 MetS and 1904 control subjects died, implying 10 deaths in the MetS group and 7 deaths in the controls per 1000 person-years at risk (fig. 1). Cox analysis showed increased mortality in the MetS group compared to the controls, hazard ratio (HR) 1.30 (95% CI: 1.20-1.40); p&amp;lt;0.001. Non-fatal CV events in the MetS group and in the controls were 32.4% vs 22.8%, respectively (p&amp;lt;0.001); HR 1.35 (CI;1.25–1.46) (fig 2). Median time (Q1, Q3) for first non-fatal CV event was 16.8 years (9.9,22.3) in the MetS group and 19.1 (12.2, 23.6) for the controls. Conclusions Results from this long-term, population-based study underline that the risk of non-fatal CVD and all-cause mortality was significantly higher in individuals with asymptomatic MetS. Present results support previous studies that early identification of MetS with screening programs might open a window of opportunity for prevention of CVD and premature death in the general population.Figure 1.All-cause mortalityFigure 1.Cardiovascular events

Integrative interpretation of cardiopulmonary exercise tests for cardiovascular risk stratification: a machine learning approach

Abstract Background and objectives Cardiopulmonary exercise testing (CPET) remains underutilized for cardiovascular (CV) risk assessment. Integrative interpretation of CPET results may improve characterization of cardiorespiratory fitness and assessment of CV risk. Therefore, we explored the clinical value of CPET-based phenomapping for CV risk stratification. Methods We retrospectively retrieved clinical data from 2280 patients with diverse CV risk (47.9% female) who underwent maximal CPET by cycle ergometry. We derived 18 key CPET indices as well as data on fatal and non-fatal CV events (median follow-up time: 5.3 years). Next, an unsupervised clustering algorithm (Gaussian Mixture modelling) subdivided the cohort in sex-specific phenogroups solely based on differences in CPET metrics. Clinical characteristics were compared across CPET phenogroups and their multivariable-adjusted association with future CV events was determined. Results 8 of the 18 CPET metrics were excluded from clustering due to high collinearity (i.e. an absolute Pearson correlation coefficient &amp;gt;0.8). Based on the remaining 10 CPET variables, the clustering algorithm subdivided the cohort in four male and four female CPET phenogroups. In both males and females, the phenogroups differed significantly in age, BMI, spirometric and CPET measurements and prevalence of hypertension, intake of antihypertensive and lipid-lowering drugs, CV disease and CV surgery (P&amp;lt;0.05 for trends). During follow-up, 278 males and 109 females experienced a CV event (43.9 and 16.2 events per 1000 years of follow-up, respectively). Compared to male phenogroup 1, male phenogroups 3 and 4 presented higher risk for incident CV events (multivariable-adjusted hazard ratio: 1.97 and 1.62; P≤0.027). Significant differences in risk for future CV events between the female phenogroups disappeared after adjustment for confounders. Conclusion Integrative CPET-based phenogrouping adequately stratified patients according to their risk for future CV events. Such phenomapping may facilitate comprehensive evaluation of CPET results and steer future CV risk management.Study flow and findings