Risk Reclassification Research Articles

Abstract 4143270: PREDICTIVE MODELS AID PHYSICIAN PROGNOSTICATION: A SECONDARY ANALYSIS EVALUATING INTEGRATED MODEL AND PHYSICIAN PROGNOSTIC ESTIMATES IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION

Background: In recent studies from a multicenter Canadian cohort of outpatients with heart failure (HF), we found that model predictions were significantly more accurate than HF cardiologists. In this study, trying to mimic practice, we evaluated the additional predictive value and clinical impact of model predictions to refine physician estimated risk of 1-year mortality by combining model and physician estimates. Methods: We included consented consecutive HF outpatients (LVEF <40%) followed at 11 HF clinics in Canada. HF cardiologists estimated patient 1-year mortality using their clinical judgment. We calculated model predicted mortality using the Seattle HF Model (SHFM). We followed patients for at least a year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using random forest survival model and cross-validation, we compared the performance SHFM and the HF cardiologist alone, and the integrated HF cardiologist and the SHFM predictions by evaluating model discrimination (c-statistic), calibration (observed vs predicted event rate), risk reclassification and clinical net benefit analyses. Results: Among 1,643 HF patients, 1-year event rate was 9% (95%CI 8%-11%). The SHFM had the adequate discrimination (c-statistic 0.76) and excellent calibration while cardiologists showed adequate discrimination (c-statistic 0.75) and poor calibration with significant risk overestimation ( Figure 1 ). When the SHFM estimates were added physician predictions, discrimination significantly improved (0.82, 95%CI 0.78-0.86) with excellent calibration. By risk reclassification analysis, among patients with events, HF cardiologist better reclassified 44% than the SHFM or the integrated model. Among patients without event, however, HF cardiologists worse risk-classified 52% in comparison to SHFM and 71% to the integrated model. By net clinical benefit analysis ( Figure 2 ), when the decision to treat involves patients with 1-year mortality of >5%, SHFM predictions would lead to higher benefit than guiding care by physician judgement. Integrating model and HF cardiologist predictions led to minimally increased benefit in comparison to SHFM alone. Conclusions: Integrating prediction from the SHFM to physician judgment or using the SHFM alone showed superior accuracy than HF cardiologist predictions, proving that model-informed care may provide more accurate prognostic information to tailor clinical decision making.

Abstract 4124289: Changes in high-sensitivity cardiac troponin I and associated cardiovascular risk: Analyses From the FOURIER Trial

Background: Circulating high-sensitivity cardiac troponin I (hs-cTnI) is associated with the risk of future cardiovascular (CV) events in stable patients (pts). Data are scarce regarding changes of hs-cTnI in a stable setting. Aims: To study baseline and changes of hs-cTnI in pts with atherosclerotic CV disease (ASCVD), and the association with risk of major CV events. Methods: We measured hs-cTnI (Abbott ARCHITECT) at baseline (BL) and 24 weeks (wks) in 20,718 pts enrolled in a nested biomarker study of the FOURIER trial, which tested the PCSK9i evolocumab vs. placebo in pts with ASCVD on statin and LDL > 70 or non-HDL > 100 mg/dL. The primary endpoint was an adjudicated composite of CV death, MI, stroke, hosp. for unstable angina, or coronary revascularization. The HR (95% CI) across percent-change of hs-cTnI was investigated in pts with quantifiable hs-cTnI at BL and 24 wks (lower limit of quantification (LLOQ) 3.6ng/L) using restricted-cubic splines and Cox-PH models, adjusted for sex, age, LDL at BL, prior MI, randomized treatment, eGFR, DM, HTN, prior HF, and BMI. A Generalized Additive Model was used to predict event rates as a function of hs-cTnI BL and absolute change, flexibly evaluated with a non-linear interaction. All models were based on 3-year follow-up using landmark analysis from 24 wks. Results: Median age was 63 yrs (25 th , 75 th percentiles: 56, 69), 75.5% were male, 86.1% had CAD, 13.7% PAD, and 19.0% a prior stroke. Of these pts, 11,021 (46.8%) had hs-cTnI > LLOQ at BL and 24 wks. The median hs-cTnI at 24 wks was 6.6ng/L (5 th , 25 th , 75 th , 95 th percentiles are: 3.7, 4.7, 11.9, 51.1 ng/L). The absolute event rate of the primary endpoint across hs-cTnI BL and depending on absolute hs-cTnI change to 24 wks is shown in Fig. A . Higher Hs-cTnI BL was associated with higher event rates (p < 0.001). Additionally, absolute reductions and increases of hs-cTnI from BL to 24 wks resulted in reduced and increased event rates, respectively, across hs-cTnI BL . Additionally, relative decrease and increase of hs-cTnI from BL to 24 wks were associated with reduced and increased relative risk, respectively (p for overall effect < 0.001, Fig. B ). Conclusion: Changes in hs-cTnI are associated with the risk of future CV events. Serial measurements of hs-cTnI may aid in reclassification of CV risk and the identification of pts whose CV risk changes with time.

Use of biomarkers of metals to improve prediction performance of cardiovascular disease mortality

BackgroundWhether including additional environmental risk factors improves cardiovascular disease (CVD) prediction is unclear. We attempted to improve CVD mortality prediction performance beyond traditional CVD risk factors by additionally using metals measured in the urine and blood and with statistical machine learning methods.MethodsOur sample included 7,085 U.S. adults aged 40 years or older from the National Health and Nutrition Examination Survey 2003–2004 through 2015–2016, linked with the National Death Index through December 31, 2019. Data were randomly split into a 50/50 training dataset used to construct CVD mortality prediction models (n = 3542) and testing dataset used as validation to assess prediction performance (n = 3543). Relative to the traditional risk factors (age, sex, race/ethnicity, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, hypertension, and diabetes), we compared models with an additional 17 blood and urinary metal concentrations. To build the prediction models, we used Cox proportional hazards, elastic-net (ENET) penalized Cox, and random survival forest methods.Results420 participants died from CVD with 8.8 mean years of follow-up. Blood lead, cadmium, and mercury were associated (p < 0.005) with CVD mortality. Including these blood metals in a Cox model, initially containing only traditional risk factors, raised the C-index from 0.845 to 0.847. Additionally, the Net Reclassification Index showed that 23% of participants received a more accurate risk prediction. Further inclusion of urinary metals improved risk reclassification but not risk discrimination.ConclusionsIncorporating blood metals slightly improved CVD mortality risk discrimination, while blood and urinary metals enhanced risk reclassification, highlighting their potential utility in improving cardiovascular risk assessments.

Plasma Phenylacetylglutamine Levels and Prognosis of Ischemic Stroke: A Multicenter Prospective Study Based on the CATIS Trial.

Phenylacetylglutamine is implicated in platelet clotting and thrombosis, but its prognostic value in ischemic stroke remains unclear. We aimed to explore the associations of plasma phenylacetylglutamine levels with adverse outcomes after ischemic stroke in a multicenter prognostic cohort study. Our multicenter prognostic cohort study included 3564 Chinese patients with ischemic stroke from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). All patients were followed up at 3 months after ischemic stroke onset. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score, 3-6) at 3 months after ischemic stroke. During 3 months of follow-up, 877 participants experienced the primary outcome. After multivariate adjustment, each 500 ng/mL increase of phenylacetylglutamine was associated with a 7% (P=0.012), 6% (P=0.016), and 6% (P=0.028) increased risk of the primary outcome, major disability, and death, respectively. The odds ratios or hazard ratios in the highest versus the lowest quartile of plasma phenylacetylglutamine were 1.62 ([95% CI, 1.18-2.23]; Ptrend=0.001) for the primary outcome, 1.62 ([95% CI, 1.16-2.24]; Ptrend=0.001) for major disability, and 2.59 ([95% CI, 1.19-5.60]; Ptrend=0.025) for death, respectively. There was a significantly worse shift in the distribution of modified Rankin Scale score at 3 months with higher phenylacetylglutamine quartiles (Ptrend=0.003). Multiple-adjusted spline regression model showed a linear relationship between phenylacetylglutamine and primary outcome (P value for linearity<0.001). The addition of plasma phenylacetylglutamine to conventional risk factors significantly improved the risk reclassification for the primary outcome (net reclassification improvement, 19.34%; P<0.001; integrated discrimination improvement, 0.23%; P=0.019). Elevated plasma phenylacetylglutamine levels at baseline were associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that phenylacetylglutamine may be a promising prognostic biomarker for ischemic stroke. Further studies are needed to investigate whether phenylacetylglutamine is a stroke-specific biomarker.

The role of coronary artery calcium score and european score2 in primary prevention of cardiovascular disease

Abstract Background There is limited evidence about the role of using coronary artery calcium (CAC) score in conjunction with the European SCORE2 (systematic coronary risk evaluation) for the identification of individuals at higher risk of cardiovascular disease. Purpose To evaluate the relationship between CAC score and the European SCORE2 for cardiovascular risk stratification in an asymptomatic population in primary prevention. Methods This is a preliminary analysis from a single-centre, prospective, randomised 1:1, controlled trial assessing the use of CAC score vs standard preventive strategies in asymptomatic individuals undergoing primary cardiovascular prevention. The 10-year risk of cardiovascular events was assessed with either SCORE2 (ages 45-69) or SCORE2-OP (ages 70-89). Subjects were classified as 1) low to moderate risk, 2) high risk, and 3) very high risk according to SCORE2/SCORE2-OP. CAC score was assessed by ECG gated low-dose computed tomography with no contrast administration. A CAC score of zero was considered to reclassify risk one level downward in high or very-high risk patients. CAC score ≥ 100 was used to reclassify risk one level upward in patients with low to moderate risk and a CAC score &amp;gt; 1000 to reclassify risk upward in subjects with high risk. Results A total of 1,252 participants: 627 in the CAC group and 625 in the control group, median age 55 yrs, 25th-75th 50-61 yrs, with availability of SCORE2 and SCORE2-OP were included in this analysis. SCORE2/SCORE 2-OP was similar in the CAC and control groups. Among the subjects in the CAC group, there was a highly significant difference in SCORE2/SCORE 2-OP between participants with CAC score = zero and those with CAC &amp;gt; zero (median 5.6, 25th-75th 3.6-8.55 vs 2.9, 1.8-4.6, p&amp;lt; 0.001) as well as between those with CAC ≥ 100 and those with CAC score &amp;lt; 100 [median 6.8, 25th-75th (10.3-4.5) vs 3.3 (2.0-5.3), p&amp;lt;0.001]. The prevalence of CAC score = zero was 75% in the low to moderate risk group, 47% in the high risk, and 20% in the very high risk, p&amp;lt;0.001. By contrast the prevalence of CAC score ≥ 100 was 7% in the low to moderate risk group, 24% in the high risk, and 45% in the very high risk, p&amp;lt; 0.001. The proportion of patients classified as low to moderate risk group was 72% with CAC score vs 59% without CAC score, high risk 23% with CAC score vs 35% without CAC score, very high risk 5% vs 6% respectively, p&amp;lt;0.001. Using CAC score risk reclassification occurred in 48% downward and 2% upward in originally classified high risk subjects, 7% upward in originally classified low to moderate risk, and 20% downward in originally classified very high risk subjects. Conclusions CAC score may lead to risk reclassification in a substantial proportion of individuals, in particular among those originally classified as high risk by the SCORE2/SCORE2-OP. The cardiovascular risk prediction accuracy of adding CAC score to SCORE2/SCORE2-OP awaits validation at long-term follow-up.

Predicting progression from coronary artery disease to heart failure in community cohorts

Abstract Background Approximately 10% of people develop heart failure (HF) within 5 years after an acute coronary event. Once ischaemic damage has occurred, the heart undergoes remodeling, which can lead to subclinical dysfunction and HF. However, remodeling varies considerably between patients and is difficult to predict. Purpose To assess whether adding genetic information to clinical factors improves the accuracy of predicting incident non-fatal/fatal HF within 5 years in people with coronary artery disease (CAD). Methods In the UK Biobank (UKB) [1], we developed a clinical risk model (predictors age, sex, ethnicity, body mass index, social deprivation, smoking, personal medical history, time since most recent CAD admission, lipids, HbA1C, creatinine, medications). Separately, we performed a genome-wide association meta-analysis of 13,360 (6,315 + 7,045) cases and 58,126 (37,245 + 20,881) non-cases from the UKB and deCODE [2] cohorts, relating common genetic variants to non-fatal/fatal HF or cardiomyopathy in people with CAD. For the current analysis of the UKB cohort, we derived a polygenic risk score using summary statistics from deCODE alone. We then compared risk estimates and assessed reclassification of 5-year risk using the clinical risk model with and without polygenic risk score, in UKB. Risk groups were &amp;lt;5%, 5-9.9%, 10-14.9%, ≥15%. Results Among people with CAD in the 5 years prior to assessment in UKB (n=8,880, mean age 61y, 27% women) or deCODE (n=10,113, mean age 66y, 34% women), 377 (4%) and 915 (9%) developed non-fatal/fatal HF over 5 years follow-up, respectively. In the UKB cohort, median 5-year risk with the clinical model was 3.2% (IQR 2-5.4%, C-statistic 0.72, 95% CI 0.70–0.74, Table 1) and plots of predicted versus observed risk showed very good calibration across deciles. The polygenic risk score was predictive of non-fatal/fatal HF in the UKB (hazard ratio 1.03, 95% CI 1.00 to 1.05 per standard deviation) with significance decreasing after adjusting for the prognostic index of the clinical risk model (hazard ratio 1.02, 95% CI 0.99 to 1.05 per standard deviation). Median 5-year risk by the clinical+polygenic model was 3.0% (IQR 1.9-5.0%). Net reclassification with the addition of the polygenic score improved accuracy of risk prediction for 3.6% of non-cases but deteriorated accuracy of risk prediction for 6% of cases. Overall net reclassification was deterioration of -0.025. Conclusion Our data suggest that common genetic variants may be associated with progression from CAD to HF, but that adding genetic data did not improve the accuracy of predicting progression from CAD to HF beyond established clinical predictors in the UKB cohort. Confirmation of these findings in deCODE and other large cohorts is warranted.

The association of inflammation, triglycerides and lipoprotein(a) with cardiovascular events in the UK Biobank

Abstract Background Recent trial data has suggested that high-sensitivity C-reactive protein (hsCRP) is, at least, as strong a predictor of future cardiovascular events as LDL cholesterol in patients on lipid-lowering therapy1,2. There are limited data however on how hsCRP and other additional risk factors perform in patients at different levels of CVD risk. Purpose To evaluate the relationship of hsCRP, triglyceride and lipoprotein(a) [Lp(a)] levels with cardiovascular events in guideline-defined, clinically distinct cohorts. Such a study will improve the understanding of CVD risk prediction and provide essential information on the role of these pathways in CVD. Methods Data from the UK Biobank were used. In accordance with the 2021 ESC CVD prevention guidelines, four risk groups were derived based on clinical data and 10-year CVD risk, calculated from the recently derived SCORE2 model (Figure 1)3. Those not falling into one of the four cohorts were excluded as further risk stratification in these individuals would not influence management. For increasing quartiles (Q) of each biomarker, hazard ratios (HR), 95% confidence intervals (CI) and p-values were calculated relative to the lowest Q, using Cox proportional hazards models, adjusted for age, sex, smoking status, systolic blood pressure, HDL cholesterol and total cholesterol. Interactions between sex and biomarker were explored. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction, and ischaemic stroke. Secondary endpoints were the individual components of the primary endpoint. Results A total of 229,339 participants were included across the four risk groups, with a total of 24,133 primary endpoint events over the mean follow-up period of 14 years. In all four groups there was a robust linear relationship of hsCRP with MACE (p&amp;lt;0.001 [Figure2]) – strongest in the secondary prevention population (Q4 v Q1 HR=1.79 [95%CI:1.60, 2.02]). Of the secondary endpoints, hsCRP was most strongly associated with cardiovascular death (Q4 v Q1 secondary prevention cohort HR=1.97 [1.68, 2.30]). Lp(a) was associated with MACE in the primary prevention cohorts only (Q4 vs Q1 high-risk cohort HR=1.35 [1.27, 1.44]), driven by its strong association with myocardial infarction (Q4 vs Q1 HR 1.61 [1.48, 1.75]) but not other secondary endpoints. After adjustment, triglyceride levels were not associated with MACE in the four cohorts. There was no evidence of sex interactions in any analysis (p&amp;gt;0.05). Conclusions After adjustment for traditional CVD risk factors, hsCRP is a more robust predictor of cardiovascular events than Lp(a) or triglycerides in both primary and secondary prevention settings. Consideration should be given to evaluating whether hsCRP, Lp(a) and other ‘non-traditional’ risk factors can improve CVD risk reclassification and/or be used to guide allocation to targeted anti-atherosclerotic therapies.Figure 1:Participant FlowFigure 2:Main effects

Deep Learning-Based Detection of Carotid Plaques Informs Cardiovascular Risk Prediction and Reveals Genetic Drivers of Atherosclerosis.

Atherosclerotic cardiovascular disease, the leading cause of global mortality, is driven by lipid accumulation and plaque formation within arterial walls. Carotid plaques, detectable via ultrasound, are a well-established marker of subclinical atherosclerosis. In this study, we trained a deep learning model to detect plaques in 177,757 carotid ultrasound images from 19,499 UK Biobank (UKB) participants (aged 47-83 years) to assess the prevalence, risk factors, prognostic significance, and genetic architecture of carotid atherosclerosis in a large population-based cohort. The model demonstrated high performance metrics with accuracy, sensitivity, specificity, and positive predictive value of 89.3%, 89.5%, 89.2%, and 82.9%, respectively, identifying carotid plaques in 45% of the population. Plaque presence and count were significantly associated with future cardiovascular events over a median follow-up period of up to 7 years, leading to improved risk reclassification beyond established clinical prediction models. A genome-wide association study (GWAS) meta-analysis of carotid plaques (29,790 cases, 36,847 controls) uncovered two novel genomic loci (p < 5×10 -8 ) with downstream analyses implicating lipoprotein(a) and interleukin-6 signaling, both targets of investigational drugs in advanced clinical development. Observational and Mendelian randomization analyses showed associations between smoking, low-density-lipoprotein (LDL) cholesterol, and high blood pressure and the odds of carotid plaque presence. Our study underscores the potential of carotid plaque assessment for improving cardiovascular risk prediction, provides novel insights into the genetic basis of subclinical atherosclerosis, and offers a valuable resource for advancing atherosclerosis research at the population scale.

Estimated glucose disposal rate, high sensitivity C-reactive protein and cardiometabolic multimorbidity in middle-aged and older Chinese adults: A nationwide prospective cohort study

AimTo explore the separate and joint association of estimated glucose disposal rate (eGDR) and high-sensitivity C-reactive protein (hsCRP) with cardiometabolic multimorbidity (CMM). MethodsA total of 6900 participants aged 45 years or older with available data on eGDR and hsCRP and without cardiometabolic diseases at baseline from the China Health and Retirement Longitudinal Study were included. CMM was defined as the coexistence of two or more cardiometabolic diseases, including heart diseases, stroke, and diabetes. ResultsDuring a median follow-up of 9.0 years, 464 (6.7 %) participants developed CMM. Low eGDR and high hsCRP separately and jointly increased the risk of CMM. The adjusted hazard ratio (HR) was 1.67 (95 % confidence interval [CI] 1.33–2.09) for low eGDR versus high eGDR, 1.43 (95 % CI 1.12–1.82) for high hsCRP versus low hsCRP) and 2.40 (95 % CI 1.77–3.27) for low eGDR plus high hsCRP versus high eGDR plus low hsCRP. The C-statistic, discriminatory power and risk reclassification significantly improved with the addition of combined eGDR and hsCRP for CMM (P < 0.001). ConclusionsLow eGDR and high hsCRP were individually and jointly associated with increased risk of incident CMM. The findings highlighted the importance of joint evaluation of eGDR and hsCRP for primary prevention of CMM.

Urinary Cytokeratin 20 as a Biomarker for AKI-CKD Transition among Patients with Acute Decompensated Heart Failure and AKI.

Predicting the risk of AKI-CKD transition remains a major challenge in management of acute decompensated heart failure and AKI. This study investigated the clinical utility of urinary cytokeratin 20 (CK20), a novel biomarker reflecting severity of histological acute tubular injury, for identifying patients at risk of AKI-CKD progression. This prospective cohort study included a Test set comprising 279 consecutive hospitalized patients with acute decompensated heart failure and AKI in 5 centers and a Validation set enrolling 206 similar patients at an external center. Urinary CK20 and seven reported renal tubular injury biomarkers at the time of AKI diagnosis were measured. The primary outcome was a composite of AKI-CKD transition 90 days after AKI or all-cause death within 90 days. The secondary outcome was AKI-CKD progression 90 days after AKI. In the Test set, 115 (41%) patients reached the primary endpoint. Concentrations of urinary CK20 peaked on the day of AKI diagnosis and remained elevated 14 days after AKI. After multivariable adjustment, the highest tertile of urinary CK20 was associated with 21-fold higher risk of the primary outcome and 29-fold higher risk of the secondary outcome. For predicting the primary and the secondary outcomes, urinary CK20 at the time of AKI diagnosis had area under the receiver-operating characteristic curves (AUC) of 0.82 (95% confidence interval [CI], 0.77-0.87) and 0.81 (95% CI, 0.75-0.87), and outperformed other reported biomarkers reflecting acute tubular injury and the risk of CKD. Adding urinary CK20 to the clinical variables improved the ability for predicting the primary outcome with an AUC of 0.90 (95% CI, 0.85-0.94), and largely improved the risk reclassification. The ability of urinary CK20 in predicting AKI-CKD transition was further confirmed in the Validation set. Urinary CK20 improved prediction of the risk for transition from AKI to CKD in patients with acute decompensated heart failure and AKI.

The role of the TAPSE/sPAP ratio as a predictor of mortality in pulmonary arterial Hypertension: Its value for patient risk stratification

BackgroundThe tricuspid annular plane systolic excursion and systolic pulmonary artery pressure (TAPSE/sPAP) ratio has been proposed as an indicator of ventriculo-arterial coupling, predicting right ventricular failure (RVF) and mortality in patients with pulmonary arterial hypertension (PAH). ObjectiveTo evaluate the usefulness of the TAPSE/sPAP ratio in predicting outcomes and improving risk stratification in patients with PAH. Methods156 patients with PAH were included. Clinical, functional, echocardiographic, and haemodynamic variables, along with the TAPSE/sPAP ratio, were analysed based on etiological PAH subgroups and outcomes. Additional statistical measures, such as the area under the curve (AUC), net reclassification index (NRI), and integrated discrimination improvement, assessed the predictive ability of TAPSE/sPAP in combination with the ESC/ERS risk score, and other risk assessment strategies (COMPERA and Reveal Lite 2). ResultsMost patients were female (86.5%), with a median age of 45.5 (IQR: 29–58) years. The TAPSE/sPAP ratio for the whole group was 0.26 (IQR: 0.190–0.347) mm/mmHg, which was similar among different aetiologies, but different between deceased and surviving patients (0.14 vs. 0.27 mm/mmHg, respectively, P<0.001). A TAPSE/sPAP ratio <0.18 mm/mmHg independently predicted mortality (AUC: 0.859, 95% CI: 0.766– 0.952; P<0.001). Integration with the ESC/ERS risk score improved predicted mortality (AUC: 0.87 vs. 0.75, p=0.002) and risk stratification, reclassifying 14.28% of events and 36.92% of non-events, with an NRI of 39.4% (P<0.001). Likewise, integration with other scores improved predicted ability of COMPERA and REVEA Lite2; COMPERA+TAPSE/sPAP (AUC: 0.837 vs 0.742; p=0.005) and REVEAL Lite 2 +TAPSE/sPAP (AUC: 0.840 vs. 0.713; p<0.001). ConclusionsA TAPSE/sPAP ratio <0.18 mm/mmHg predicts mortality in PAH. The combination of the TAPSE/sPAP ratio with the ESC/ERS risk score improved risk stratification, and reclassification emphasizing the potential of ESC/ERS+TAPSE/sPAP as a valuable tool for risk assessment and clinical decision-making in PAH patients. Integration of TAPSE/sPAP ratio with other scores (COMPERA and (REVEAL Lite 2) also improved the risk stratification and reclassification of these risk scores.

Risk of Stroke and Incident Atrial Fibrillation in Patients in Sinus Rhythm With Nonischemic Dilated Cardiomyopathy

Background: Non-ischemic dilated cardiomyopathy (NIDCM) is associated with an increased risk of atrial fibrillation (AF) and stroke, especially in patients with high CHA2DS2-VASc. We aimed to identify variables associated with incident AF or stroke using left atrial (LA) deformation analysis and its prognostic value added to CHA2DS2-VASc score. Patients with NIDCM and LVEF <50% in sinus rhythm were included between January 2015 and December 2019. LA volume index (LAVI) and atrial strain were used in combination with the CHA2DS2-VAS score to predict ischemic stroke or incident AF. Proportional hazards Cox regression was used to provide hazard ratios (HR). There were 338 patients included. After a median follow-up of 3.6 years, the endpoint occurred in 41 (12.1%) patients. LAVI outperformed other echocardiographic parameters, with significant improvement in risk reclassification compared to CHA2DS2-VASc alone (net reclassification index 0.6, increase in Harrell's C from 0.63 to 0.73, P=0.003) and remained significant after multivariate adjustment. LAVI was associated with both components of the endpoint separately. The best cutoff for LAVI was 44 ml/m2. LAVI ≥44ml/m2 increased the risk of the endpoint among those with CHA2DS2-VASc ≥3 (HR=6.0, 95%CI 2.6-13.5), but not in those with CHA2DS2-VASc <3 (HR=1.2, 95%CI 0.3-4.5). Competing risk analysis did not alter the results. In conclusion, LAVI might be used to assess the risk of incident AF or stroke in NIDCM. Patients with LAVI ≥44 ml/m2 and CHA2DS2-VASc ≥3 could be at high risk of AF and stroke and may benefit from more intensive surveillance.

Body Roundness Index Trajectories and the Incidence of Cardiovascular Disease: Evidence From the China Health and Retirement Longitudinal Study.

Several previous cross-sectional studies suggested that body roundness index (BRI) may be associated with cardiovascular disease (CVD). However, the association should be further validated. Our study aimed to assess the association of the BRI trajectories with CVD among middle-aged and older Chinese people in a longitudinal cohort. A total of 9935 participants from the CHARLS (China Health and Retirement Longitudinal Study) with repeated BRI measurements from 2011 to 2016 were included. The BRI trajectories were identified by group-based trajectory modeling. The primary outcome was incident CVD (stroke or cardiac events), which occurred in 2017 to 2020. Cox proportional hazards regression models were used to examine the association of BRI trajectories with CVD risk. Participants were divided into 3 BRI trajectories, named the low-stable BRI trajectory, moderate-stable BRI trajectory and high-stable BRI trajectory, accounting for 49.81%, 42.35%, and 7.84% of the study population, respectively. Compared with participants in the low-stable BRI trajectory group, those in the moderate-stable and high-stable BRI trajectory groups had an increased risk of CVD, with multivariable adjusted hazard ratios of 1.22 (95% CI, 1.09-1.37) and 1.55 (95% CI, 1.26-1.90), respectively. Furthermore, simultaneously adding the BRI trajectory to the conventional risk model improved CVD risk reclassification (all P<0.05). A higher BRI trajectory was associated with an increased risk of CVD. The BRI can be included as a predictive factor for CVD incidence.

The prognostic impact of malnutrition on the outcomes of patients with vertebrobasilar artery occlusion following endovascular treatment

Background and purposeMalnutrition is associated with poor outcomes in different diseases. Our aim was to investigate whether measures of malnutrition could be used to predict 90-day outcomes in patients with vertebrobasilar artery occlusion (VBAO) undergoing endovascular treatment (EVT). MethodsWe retrospectively analyzed patients with VBAO who received EVT at three comprehensive stroke centers. Malnutrition was assessed using the controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI). Primary outcome was good functional outcome defined as modified Rankin Scale (mRS) 0–3 measured at 90 days. ResultsA total of 285 patients were enrolled, of which 260 (91.22 %) met the requirements. According to the CONUT, GNRI, and PNI scores, the proportions of patients classified as moderately or severely malnourished were 7.3 %, 3.08 %, and 35 %, respectively. In the multivariate regression model after adjusting for potential confounders, malnutrition (severe risk versus normal nutritional status) was significantly associated with an increased risk of poor prognosis for CONUT scores (adjusted odds ratio [OR]14.91, 95 %CI, 1.69 - 131.71; P = 0.015), GNRI scores (adjusted [OR] 10.67, 1.17 - 96.93; P = 0.036) and PNI scores (adjusted [OR] 4.61, 2.28 - 9.31; P < 0.001). Similar results were obtained when malnutrition scores were analyzed as continuous variables. Adding the 3 malnutrition measures to the risk reclassification that included traditional risk factors significantly improved the predictive value of 3-month poor prognosis. ConclusionsOur study showed that malnutrition may be associated with poor prognosis within 3 months of EVT in patients with VBAO.

Tailoring Risk Prediction Models to Local Populations.

Risk estimation is an integral part of cardiovascular care. Local recalibration of guideline-recommended models could address the limitations of existing tools. To provide a machine learning (ML) approach to augment the performance of the American Heart Association's Predicting Risk of Cardiovascular Disease Events (AHA-PREVENT) equations when applied to a local population while preserving clinical interpretability. This cohort study used a New England-based electronic health record cohort of patients without prior atherosclerotic cardiovascular disease (ASCVD) who had the data necessary to calculate the AHA-PREVENT 10-year risk of developing ASCVD in the event period (2007-2016). Patients with prior ASCVD events, death prior to 2007, or age 79 years or older in 2007 were subsequently excluded. The final study population of 95 326 patients was split into 3 nonoverlapping subsets for training, testing, and validation. The AHA-PREVENT model was adapted to this local population using the open-source ML model (MLM) Extreme Gradient Boosting model (XGBoost) with minimal predictor variables, including age, sex, and AHA-PREVENT. The MLM was monotonically constrained to preserve known associations between risk factors and ASCVD risk. Along with sex, race and ethnicity data from the electronic health record were collected to validate the performance of ASCVD risk prediction in subgroups. Data were analyzed from August 2021 to February 2024. Consistent with the AHA-PREVENT model, ASCVD events were defined as the first occurrence of either nonfatal myocardial infarction, coronary artery disease, ischemic stroke, or cardiovascular death. Cardiovascular death was coded via government registries. Discrimination, calibration, and risk reclassification were assessed using the Harrell C index, a modified Hosmer-Lemeshow goodness-of-fit test and calibration curves, and reclassification tables, respectively. In the test set of 38 137 patients (mean [SD] age, 64.8 [6.9] years, 22 708 [59.5]% women and 15 429 [40.5%] men; 935 [2.5%] Asian, 2153 [5.6%] Black, 1414 [3.7%] Hispanic, 31 400 [82.3%] White, and 2235 [5.9%] other, including American Indian, multiple races, unspecified, and unrecorded, consolidated owing to small numbers), MLM-PREVENT had improved calibration (modified Hosmer-Lemeshow P > .05) compared to the AHA-PREVENT model across risk categories in the overall cohort (χ23 = 2.2; P = .53 vs χ23 > 16.3; P < .001) and sex subgroups (men: χ23 = 2.1; P = .55 vs χ23 > 16.3; P < .001; women: χ23 = 6.5; P = .09 vs. χ23 > 16.3; P < .001), while also surpassing a traditional recalibration approach. MLM-PREVENT maintained or improved AHA-PREVENT's calibration in Asian, Black, and White individuals. Both MLM-PREVENT and AHA-PREVENT performed equally well in discriminating risk (approximate ΔC index, ±0.01). Using a clinically significant 7.5% risk threshold, MLM-PREVENT reclassified a total of 11.5% of patients. We visualize the recalibration through MLM-PREVENT ASCVD risk charts that highlight preserved risk associations of the original AHA-PREVENT model. The interpretable ML approach presented in this article enhanced the accuracy of the AHA-PREVENT model when applied to a local population while still preserving the risk associations found by the original model. This method has the potential to recalibrate other established risk tools and is implementable in electronic health record systems for improved cardiovascular risk assessment.

Serum Soluble Corin and Long-Term Clinical Outcomes After Acute Ischemic Stroke.

Corin plays important roles in the regulation of blood volume and pressure and cardiac function by activating natriuretic peptide pathway, exerting multiple cardioprotective effects. But the impacts of soluble corin on clinical outcomes after ischemic stroke are unclear. We aimed to investigate the associations between serum soluble corin and long-term clinical outcomes after acute ischemic stroke. We measured the concentrations of serum soluble corin in 3162 participants (2010 men and 1152 women) from the China Antihypertensive Trial in Acute Ischemic Stroke. The clinical outcomes were recurrent stroke, cardiovascular events, all-cause mortality, and unfavorable functional outcome within 24 months after stroke. Risk reclassification for study clinical outcomes of models with soluble corin were evaluated. Serum soluble corin was inversely associated with recurrent stroke, cardiovascular events, and unfavorable functional outcome after ischemic stroke. After adjusting for multiple covariates, each additional SD of log-corin was associated with a 21% (95% CI, 11-30), 16% (95% CI, 6-26), and 12% (95% CI, 3-21) decreased risk for recurrent stroke, cardiovascular events, and unfavorable functional outcome, respectively. Furthermore, the addition of soluble corin to the basic model with conventional risk factors significantly improved risk discrimination for recurrent stroke, cardiovascular events, and the composite outcome of all-cause mortality and cardiovascular events, as shown by C-statistics (all P<0.05). Serum soluble corin was associated with decreased risks of long-term clinical outcomes, and may be a promising prognostic biomarker for risk stratification in patients with acute ischemic stroke.

MPATH-Dx Version 2.0 Schema for Melanocytic Lesions: A Robust Tool for Standardized Diagnostic Reporting

The new revised MPATH-Dx (Version 2.0) reporting schema for melanocytic lesions is presented herein. Principal changes include the simplification of the previous five-class Version 1.0 to a four-class hierarchy of melanocytic lesions to improve diagnostic agreement and to provide more explicit guidance in the management of patients. Version 2.0 also has clearly defined histopathological criteria for classification of Class I and II lesions now designated as low-grade (mild to moderate) atypia and high-grade (high-end moderate to severe) atypia, respectively. This new revised schema, also includes specific provisions for the less common WHO pathways to melanoma, provides guidance for classifying "intermediate" Class II tumors (melanocytomas), and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as a neoplasm falling short of fully-evolved melanoma.

The critical role of cardiorespiratory fitness in disease prevention.

Cardiorespiratory fitness (CRF) has been increasingly recognized in recent years as an important predictor of risk for adverse outcomes in numerous chronic conditions. In fact, a growing body of epidemiological and clinical evidence demonstrates that CRF is a potentially stronger predictor of mortality than established risk factors such as smoking, hypertension, hyperlipidemia, and type 2 diabetes. Moreover, adding CRF to these traditional risk factors significantly improves the reclassification of risk for adverse outcomes. The utility of CRF now extends far beyond all-cause and cardiovascular mortality to include the prevention and treatment of numerous other chronic conditions; CRF has been demonstrated to have a mitigating influence in as many as 40 such conditions. Herein we discuss the impact of CRF in the prevention of chronic disease in both adults and children. This discussion includes recent data on interactions between CRF and aging, obesity, statin use, incidence of diabetes, and the impact of CRF and physical activity patterns in adolescents including mental health, scholastic achievement, and cardiometabolic health. Finally, we discuss how CRF, as an essential vital sign, can be implemented in clinical practice.

18FFlutemetamol-PET Aided Classification of Cerebral Amyloid Angiopathy: A Multicenter Study.

Cerebral amyloid angiopathy (CAA)-related features on neuroimaging often coexist with signs of arteriolosclerosis-small vessel disease on neuroimaging in people with intracranial hemorrhage (ICH). This study aimed at defining the value of amyloid pathology detected by 18Fflutemetamol PET in reclassification and stratification of risk of bleeding in people with mixed CAA-arteriolosclerosis features. We included consecutive patients admitted to 2 institutions (2018-2023) with spontaneous symptomatic ICH, subarachnoid hemorrhage (SAH), transient focal neurologic episodes (TFNE), or cognitive impairment and MRI showing CAA hallmarks. All patients underwent brain magnetic resonance imaging (MRI) with susceptibility weighted imaging and 18Fflutemetamol PET imaging and were followed up for at least 1 year. We compared cases with CAA and arteriolosclerosis + CAA features and defined long-term outcomes (composite outcome including death, ICH, ischemic stroke, SAH, TFNE) depending on PET status (CAA/amyloid pathology vs arteriolosclerosis-predominant groups). Among 47 patients, according to PET and MRI imaging, 38 patients were reclassified in the CAA/amyloid pathology group and 9 in the arteriolosclerosis-predominant group, with similar cardiovascular risk factors but a significantly higher lobar microbleed burden for the former group. The CAA/amyloid pathology group had higher rates of composite outcome (43.9 vs 11.1 events per 100 patient-year; p = 0.039) and ICH (36.5 vs 5.6 events per 100 patient-years; p = 0.04) compared with the arteriolosclerosis-predominant group. 18FFlutemetamol PET imaging can help in reclassification of mixed arteriolosclerosis + CAA into CAA/amyloid pathology and arteriolosclerosis-predominant, with implications on long-term risk of recurrent events. This study provides Class IV evidence that 18Fflutemetamol PET can distinguish between CAA + arteriolosclerosis and arteriolosclerosis-predominant pathology.

Elevated CA125 values predict adverse outcomes in acute heart failure.

Abstract. In acute heart failure (AHF), elevated carbohydrate antigen 125 (CA125) and N-terminal pro-B-type natriuretic peptide (NTproBNP) have been shown to correlate with adverse events. We sought to quantify their prognostic usefulness in predicting the six-month combined death/heart failure readmis-sion endpoint. The study included 352 patients admitted for AHF. The primary endpoint was the six-month combined endpoint of death/AHF rehospitaliza-tion. CA125 and NTproBNP were dichotomized according to the best cut-offs to predict the six-month primary endpoint. The independent association of CA125 and NTproBNP with the primary endpoint was assessed by multivari-ate Cox regression analysis, and their incremental prognostic utility was evalu-ated by net reclassification improvement (NRI) and integrated discrimination improvement (IDI) index. Forty-seven (13.4%) deaths and 113 (32.1%) AHF rehospitalizations were identified at the six-month follow-up. The subjects with CA125≥39.7 U/mL and NTproBNP≥3900 pg/mL had significantly higher cu-mulative event rates (56.1% vs. 33.3% and 53.3% vs. 33.8%, both p&lt;0.001). Elevated CA125 (HR 1.93; 95% CI [1.32-2.83]; p=0.001) was associated with a higher HR (hazard ratio) than NTproBNP≥3900 pg/mL (HR 1.71; 95% CI [1.19-2.48]; p=0.004) after adjusting for established risk factors. Elevated CA125 still independently predicted adverse events when CA125 and NTproB-NP entered the same multivariate model. Furthermore, risk reclassification analyses demonstrated significant improvements in NRI of 22.3% (p=0.014) and IDI of 2.7% (p=0.012) when adding CA125 to the base model + NTproBNP. Elevated CA125 and NTproBNP predicted adverse outcomes in AHF patients. CA125 added prognostic value to NTproBNP; thus, their combination conferred greater predictive capacity.