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A prediction rule for severe adverse events in all inpatients with community-acquired pneumonia: a multicenter observational study.
Sakakibara, T, Shindo, Y, Kobayashi, D, Sano, M, Okumura, J, Murakami, Y, Takahashi, K, Matsui, S, Yagi, T, Saka, H, et al
BMC pulmonary medicine. 2022;(1):34
Abstract
BACKGROUND Prediction of inpatients with community-acquired pneumonia (CAP) at high risk for severe adverse events (SAEs) requiring higher-intensity treatment is critical. However, evidence regarding prediction rules applicable to all patients with CAP including those with healthcare-associated pneumonia (HCAP) is limited. The objective of this study is to develop and validate a new prediction system for SAEs in inpatients with CAP. METHODS Logistic regression analysis was performed in 1334 inpatients of a prospective multicenter study to develop a multivariate model predicting SAEs (death, requirement of mechanical ventilation, and vasopressor support within 30 days after diagnosis). The developed ALL-COP-SCORE rule based on the multivariate model was validated in 643 inpatients in another prospective multicenter study. RESULTS The ALL-COP SCORE rule included albumin (< 2 g/dL, 2 points; 2-3 g/dL, 1 point), white blood cell (< 4000 cells/μL, 3 points), chronic lung disease (1 point), confusion (2 points), PaO2/FIO2 ratio (< 200 mmHg, 3 points; 200-300 mmHg, 1 point), potassium (≥ 5.0 mEq/L, 2 points), arterial pH (< 7.35, 2 points), systolic blood pressure (< 90 mmHg, 2 points), PaCO2 (> 45 mmHg, 2 points), HCO3- (< 20 mmol/L, 1 point), respiratory rate (≥ 30 breaths/min, 1 point), pleural effusion (1 point), and extent of chest radiographical infiltration in unilateral lung (> 2/3, 2 points; 1/2-2/3, 1 point). Patients with 4-5, 6-7, and ≥ 8 points had 17%, 35%, and 52% increase in the probability of SAEs, respectively, whereas the probability of SAEs was 3% in patients with ≤ 3 points. The ALL-COP SCORE rule exhibited a higher area under the receiver operating characteristic curve (0.85) compared with the other predictive models, and an ALL-COP SCORE threshold of ≥ 4 points exhibited 92% sensitivity and 60% specificity. CONCLUSIONS ALL-COP SCORE rule can be useful to predict SAEs and aid in decision-making on treatment intensity for all inpatients with CAP including those with HCAP. Higher-intensity treatment should be considered in patients with CAP and an ALL-COP SCORE threshold of ≥ 4 points. TRIAL REGISTRATION This study was registered with the University Medical Information Network in Japan, registration numbers UMIN000003306 and UMIN000009837.
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Association of metabolomic markers and response to nutritional support: A secondary analysis of the EFFORT trial using an untargeted metabolomics approach.
Struja, T, Wolski, W, Schapbach, R, Mueller, B, Laczko, E, Schuetz, P
Clinical nutrition (Edinburgh, Scotland). 2021;(9):5062-5070
Abstract
BACKGROUND & AIMS The EFFORT trial reported a substantial risk reduction for adverse events and mortality in medical in-patients receiving a nutritional support intervention. With the use of an untargeted metabolomics approach, we investigated the prognostic and therapeutic potential of metabolomic markers to understand, whether there are distinct metabolic patterns associated with malnutrition risk as assessed by the Nutritional Risk screening (NRS 2002) score, the risk of 30-day mortality and the response to nutritional support, respectively. METHODS Out of the 2088 samples we randomly selected 120 blood samples drawn on day 1 after hospital admission and before treatment initiation. Samples were stratified by NRS 2002, treatment allocation (intervention vs. control), and mortality at 30 days, but not on the type of medical illness. We performed untargeted analysis by liquid chromatography mass spectrometry (LC-MS/MS). RESULTS We measured 1389 metabolites in 120 patients of which 81 (67.5%) survived until day 30. After filtering, 371 metabolites remained, and 200 were matched to one or more Human Metabolome Data Base (HMDB) entries. Between group analysis showed a slight distinction between the treatment groups for patients with a NRS 3, but not for those with NRS 4 and ≥ 5. C-statistic between those who died and survived at day 30 ranged from 0.49 (95% confidence interval 0.35-0.68) for a combination of 5 metabolites/predictors to 0.66 (95% confidence interval 0.53-0.79) for a combination of 100 metabolites. Pathway analysis found significant enrichment in the pathways for nitrogen, vitamin B3 (nicotinate and nicotinamide), leukotriene, and arachidonic acid metabolisms in nutritional support responders compared to non-responders. CONCLUSION In our heterogenous population of medical inpatients with different illnesses and comorbidities, metabolomic markers showed little prognostic and therapeutic potential for better phenotyping malnutrition and response to nutritional therapy. Future studies should focus on more selected patient populations to understand whether a metabolomic approach can advance the nutritional care of patients.
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Hypertensive Retinopathy and the Risk of Stroke Among Hypertensive Adults in China.
Chen, X, Liu, L, Liu, M, Huang, X, Meng, Y, She, H, Zhao, L, Zhang, J, Zhang, Y, Gu, X, et al
Investigative ophthalmology & visual science. 2021;(9):28
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Abstract
PURPOSE This study aimed to investigate the association between hypertensive retinopathy and the risk of first stroke, examine possible effect modifiers in hypertensive patients, and test the appropriateness of the Keith-Wagener-Barker (KWB) classification for predicting stroke risk. METHODS In total, 9793 hypertensive participants (3727 males and 6066 females) without stroke history from the China Stroke Primary Prevention Trial were included in this study. The primary outcome was first stroke. RESULTS Over a median follow-up of 4.4 years, 592 participants experienced their first stroke (509 ischemic, 77 hemorrhagic, and six unclassifiable strokes). In total, 5590 participants were diagnosed with grade 1 retinopathy (57.08%), 1466 with grade 2 retinopathy (14.97%), 231 with grade 3 retinopathy (2.36%), and three with grade 4 retinopathy (0.03%). Grades 1 and 2 were merged and classified as mild retinopathy, and grades 3 and 4 were merged and classified as severe retinopathy. There was a significant positive association between hypertensive retinopathy and the risk of first stroke and first ischemic stroke, and no effect modifiers were found. The hazard ratios (HRs) for first stroke were as follows: mild versus no retinopathy, 1.26 (95% confidence interval [CI], 1.01-1.58, P = 0.040), and severe versus no retinopathy, 2.40 (95% CI, 1.49-3.84, P < 0.001). The HRs for ischemic stroke were as follows: severe versus no retinopathy, 2.35 (95% CI, 1.41-3.90, P = 0.001), and nonsignificantly increased HRs for mild versus no retinopathy, 1.26 (95% CI, 0.99-1.60, P = 0.057). CONCLUSIONS There was a significant positive association between hypertensive retinopathy and the risk of first stroke in patients with hypertension, indicating that hypertensive retinopathy may be a predictor of the risk of stroke. A simplified two-grade classification system based on the KWB classification is recommended for predicting stroke risk.
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Clinical risk predictors in atrial fibrillation patients following successful coronary stenting: ENTRUST-AF PCI sub-analysis.
Goette, A, Eckardt, L, Valgimigli, M, Lewalter, T, Laeis, P, Reimitz, PE, Smolnik, R, Zierhut, W, Tijssen, JG, Vranckx, P
Clinical research in cardiology : official journal of the German Cardiac Society. 2021;(6):831-840
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AIMS: This subgroup analysis of the ENTRUST-AF PCI trial (ClinicalTrials.gov Identifier: NCT02866175; Date of registration: August 2016) evaluated type of AF, and CHA2DS2-VASc score parameters as predictors for clinical outcome. METHODS Patients were randomly assigned after percutaneous coronary intervention (PCI) to either edoxaban (60 mg/30 mg once daily [OD]; n = 751) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist [VKA] (n = 755) plus a P2Y12 inhibitor and aspirin (100 mg OD, for 1-12 months). The primary outcome was a composite of major/clinically relevant non-major bleeding (CRNM) within 12 months. The composite efficacy endpoint consisted of cardiovascular death, stroke, systemic embolic events, myocardial infarction (MI), and definite stent thrombosis. RESULTS Major/CRNM bleeding event rates were 20.7%/year and 25.6%/year with edoxaban and warfarin, respectively (HR [95% CI]: 0.83 [0.654-1.047]). The event rates of composite outcome were 7.26%/year and 6.86%/year, respectively (HR [95% CI]): 1.06 [0.711-1.587]), and of overall net clinical benefit were 12.48%/year and 12.80%/year, respectively (HR [(95% CI]: 0.99 [(0.730; 1.343]). Increasing CHA2DS2-VASc score was associated with increased rates of all outcomes. CHA2DS2-VASc score ≥ 5 was a marker for stent thrombosis. Paroxysmal AF was associated with a higher occurrence of MI (4.87% versus 2.01%, p = 0.0024). CONCLUSION After PCI in AF patients, increasing CHA2DS2-VASc score was associated with increased bleeding rates and CHA2DS2-VASc score (≥ 5) predicted the occurrence of stent thrombosis. Paroxysmal AF was associated with MI. These findings may have important clinical implications in AF patients.
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Derivation of a Coronary Age Calculator Using Traditional Risk Factors and Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis.
Blaha, MJ, Naazie, IN, Cainzos-Achirica, M, Dardari, ZA, DeFilippis, AP, McClelland, RL, Mirbolouk, M, Orimoloye, OA, Dzaye, O, Nasir, K, et al
Journal of the American Heart Association. 2021;(6):e019351
Abstract
Background The optimal method for communicating coronary heart disease (CHD) risk to individual patients is not yet clear. Recent research supports the concept of "coronary age" for more effective risk communication. We defined an individual's coronary age as the age at which an average healthy individual would have an equivalent estimated CHD risk as that calculated for the index individual, building on our previously validated MESA (Multi-Ethnic Study of Atherosclerosis) 10-year CHD Risk Score equations with and without coronary artery calcium (CAC). Methods and Results We derived a coronary age by (1) calculating the MESA 10-year CHD risk; (2) mathematically setting this equal to an equation describing risk of an average healthy MESA participant, as a function of age; and (3) solving for age. The risk discrimination of the resultant coronary age was compared with that of chronological age, the MESA CHD Risk Score, and CAC alone. Approximately 95% of coronary age values ranged from 30 years less to 30 years higher than chronological age. Although the mean chronological age of individuals experiencing CHD events compared with those free of events was 67.4 versus 61.8 years, the difference in coronary age including CAC was larger (80.6 versus 62.8 years). Coronary age with CAC had identical predictive ability to that of MESA CHD Risk Score and outperformed chronological age and CAC alone. Conclusions The newly derived coronary age is a convenient transformation of MESA CHD Risk, retaining very good risk discrimination. This easy-to-communicate tool will be available for patients and clinicians, potentially facilitating risk communication in routine care.
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Contemporary Management of Severe Symptomatic Aortic Stenosis.
Eugène, M, Duchnowski, P, Prendergast, B, Wendler, O, Laroche, C, Monin, JL, Jobic, Y, Popescu, BA, Bax, JJ, Vahanian, A, et al
Journal of the American College of Cardiology. 2021;(22):2131-2143
Abstract
BACKGROUND There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age-adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians.
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Maternal and Perinatal Factors Associated With Kawasaki Disease Among Offspring in Taiwan.
Chang, CL, Lin, MC, Lin, CH, Ko, TM
JAMA network open. 2021;(3):e213233
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This case-control study investigates the association of perinatal factors and maternal autoimmune diseases with the development of Kawasaki disease using the Taiwan Maternal and Child Health Database.
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Does Lowering Low-Density Lipoprotein Cholesterol With Statin Restore Low Risk in Middle-Aged Adults? Analysis of the Observational MESA Study.
Liu, K, Wilkins, JT, Colangelo, LA, Lloyd-Jones, DM
Journal of the American Heart Association. 2021;(11):e019695
Abstract
Background It is unclear if statin therapy in midlife can restore low cardiovascular risk in hypercholesterolemic individuals. Methods and Results At baseline, we grouped 5687 MESA (Multi-Ethnic Study of Atherosclerosis) participants aged ≥50 years without clinical cardiovascular disease (CVD) by Adult Treatment Panel III statin treatment recommendation and statin treatment status. We used Cox regression to compare the risks for coronary heart disease and CVD between the untreated group with low-density lipoprotein cholesterol (LDL-C) <100 mg/dL (reference) and other groups, adjusting for CVD risk factors. We also grouped participants by LDL-C level (< or ≥100 mg/dL), coronary artery calcium score (0 or >0 Agatston units), and statin status (untreated or treated) with the untreated LDL-C <100 mg/dL and coronary artery calcium=0 Agatston units as the reference. There were 567 coronary heart disease and 848 CVD events over 15 years of follow-up. The hazard ratios (HRs) for coronary heart disease and CVD in the group with statin-treated LDL-C <100 mg/dL were 1.16 (95% CI, 0.85-1.58) and 1.02 (95% CI, 0.78-1.32), respectively. However, participants with coronary artery calcium >0 Agatston units, treated to LDL-C <100 mg/dL had HRs of 2.6 (95% CI, 1.7-4.2) for coronary heart disease and 1.8 (95% CI, 1.2-2.6) for CVD. Conclusions Individuals treated with statins to LDL-C <100 mg/dL had similar levels of risk for atherosclerotic CVD as individuals with untreated LDL-C <100 mg/dL. However, individuals with coronary artery calcium >0 Agatston units have substantially higher risks despite lipid-lowering therapy, suggesting that statin treatment in midlife may not restore a low-risk state in primary prevention patients with established coronary atherosclerosis.
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Effect of the Million Hearts Cardiovascular Disease Risk Reduction Model on Initiating and Intensifying Medications: A Prespecified Secondary Analysis of a Randomized Clinical Trial.
Peterson, GG, Pu, J, Magid, DJ, Barterian, L, Kranker, K, Barna, M, Conwell, L, Rose, A, Blue, L, Markovitz, A, et al
JAMA cardiology. 2021;(9):1050-1059
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IMPORTANCE The Million Hearts Cardiovascular Disease (CVD) Risk Reduction Model pays provider organizations for measuring and reducing Medicare patients' cardiovascular risk. OBJECTIVE To assess whether the model increases the initiation or intensification of antihypertensive medications or statins among patients with blood pressure or low-density lipoprotein (LDL) cholesterol levels above guideline thresholds for treatment intensification. DESIGN, SETTING, AND PARTICIPANTS This prespecified secondary analysis of a cluster-randomized, pragmatic trial included primary care and cardiology practices, health care centers, and hospital-based outpatient departments across the US. Participants included Medicare patients who were enrolled into the model in 2017 by participating organizations and who were at high risk and at medium risk of a myocardial infarction or stroke in 10 years. Patient outcomes were analyzed for 1 year postenrollment (through December 2018) using an intent-to-treat design. Analysis began November 2019. INTERVENTIONS US Centers for Medicare & Medicaid Services paid organizations for risk stratifying Medicare patients and reducing CVD risk among high-risk patients through discussing risk scores, developing individualized risk reduction plans, and following up with patients twice yearly. MAIN OUTCOMES AND MEASURES Initiating or intensifying statin or antihypertensive therapy within 1 year of enrollment, measured in Medicare Part D claims, and LDL cholesterol and systolic blood pressure levels approximately 1 year after enrollment, measured in usual care and reported to Centers for Medicare & Medicaid Services via a data registry (data complete for 51% of high-risk enrollees). The study's primary outcome (incidence of first-time myocardial infarction and stroke) is not reported because the trial is ongoing. RESULTS A total of 330 primary care and cardiology practices, health care centers, and hospital-based outpatient departments and 125 436 Medicare patients were included in this analysis. High-risk patients in the intervention group had a mean (SD) age of 74 (4.1), 15 213 (63%) were male, 21 657 (90%) were receiving antihypertensive medication at baseline, and 16 558 (69%) were receiving statins. Almost all (21 791 [91%]) high-risk intervention group patients had above-threshold systolic blood pressure level (>130 mm Hg), LDL cholesterol level (>70 mg/dL), or both. Patients in the intervention group with these risk factors were more likely than control patients (8127 [37.3%] vs 4753 [32.4%]; adjusted difference in percentage points, 4.8; 95% CI, 2.9-6.7; P < .001) to initiate or intensify statins or antihypertensive medication. Centers for Medicare & Medicaid Services did not pay for CVD risk reduction for medium-risk enrollees, but initiation or intensification rates for these enrollees were also higher in the intervention vs control groups (12 668 [27.9%] vs 7544 [24.8%]; adjusted difference in percentage points, 3.1; 95% CI, 1.9-4.3; P < .001). Among high-risk enrollees with clinical data approximately 1 year after enrollment, LDL cholesterol level was slightly lower in the intervention vs control groups (mean [SD], 89 [31.8] vs 91 [32.1] mg/dL; adjusted difference in percentage points, -1.8; 95% CI, -2.9 to -0.6; P = .002), as was systolic blood pressure (mean [SD], 133 [15.7] vs 135 [16.4] mm Hg; adjusted difference in percentage points, -1.7; 95% CI, -2.8 to -0.6; P = .003). CONCLUSIONS AND RELEVANCE In this study, a pay-for-performance model led to modest increases in the use of CVD medications in a range of organizations, despite high medication use at baseline.
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Plasma Omega-3 Fatty Acids and the Risk of Cardiovascular Events in Patients After an Acute Coronary Syndrome in MERLIN-TIMI 36.
Zelniker, TA, Morrow, DA, Scirica, BM, Furtado, JD, Guo, J, Mozaffarian, D, Sabatine, MS, O'Donoghue, ML
Journal of the American Heart Association. 2021;(8):e017401
Abstract
Background Plasma omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been shown to be inversely correlated with the risk of cardiovascular death in primary prevention. The risk relationship in the setting of an acute coronary syndrome is less well established. Methods and Results Baseline plasma ω3-PUFA composition (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) was assessed through gas chromatography with flame ionization detection in a case-cohort study involving 203 patients with cardiovascular death, 325 with myocardial infarction, 271 with ventricular tachycardia, and 161 with atrial fibrillation, and a random sample of 1612 event-free subjects as controls from MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation-Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36), a trial of patients hospitalized with non-ST-segment-elevation -acute coronary syndrome. After inverse-probability-weighted multivariable adjustment including all traditional risk factors, a higher relative proportion of long-chain ω3-PUFAs (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid) were associated with 18% lower odds of cardiovascular death (adjusted [adj] odds ratio [OR] per 1 SD, 0.82; 95% CI, 0.68-0.98) that was primarily driven by 27% lower odds of sudden cardiac death (adj OR per 1 SD, 0.73; 95% CI, 0.55-0.97). Long-chain ω3-PUFA levels in the top quartile were associated with 51% lower odds of cardiovascular death (adj OR 0.49; 95% CI, 0.27-0.86) and 63% lower odds of sudden cardiac death (adj OR, 0.37; 95% CI, 0.16-0.56). An attenuated relationship was seen for α-linolenic acid and subsequent odds of cardiovascular (adj OR, 0.92; 95% CI, 0.74-1.14) and sudden cardiac death (adj OR, 0.91; 95% CI, 0.67-1.25). No significant relationship was observed between any ω3-PUFAs and the odds of cardiovascular death unrelated to sudden cardiac death, myocardial infarction, atrial fibrillation, or early post-acute coronary syndrome ventricular tachycardia. Conclusions In patients after non-ST-segment-elevation-acute coronary syndrome, plasma long-chain ω3-PUFAs are inversely associated with lower odds of sudden cardiac death, independent of traditional risk factors and lipids. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00099788.