scholarly journals Large‐Scale Plasma Protein Profiling of Incident Myocardial Infarction, Ischemic Stroke, and Heart Failure

Author(s):  
Lars Lind ◽  
Daniela Zanetti ◽  
Martin Ingelsson ◽  
Stefan Gustafsson ◽  
Johan Ärnlöv ◽  
...  

Background We recently reported a link between plasma levels of 2 of 84 cardiovascular disease (CVD)–related proteins and the 3 major CVDs, myocardial infarction, ischemic stroke, and heart failure. The present study investigated whether measurement of almost 10 times the number of proteins could lead to discovery of additional risk markers for CVD. Methods and Results We measured 742 proteins using the proximity extension assay in 826 male participants of ULSAM (Uppsala Longitudinal Study of Adult Men) who were free from CVD at the age of 70 years. Cox proportional hazards models were adjusted for age only, as well as all traditional risk factors. During a 12.5‐year median follow‐up (maximal, 22.0 years), 283 incident CVDs occurred. Forty‐one proteins were significantly (false discovery rate <0.05) related to the combined end point of incident CVD, with N‐terminal pro–brain natriuretic peptide as the top finding, while 53 proteins were related to incident myocardial infarction. A total of 13 and 16 proteins were significantly related to incident ischemic stroke and heart failure, respectively. Growth differentiation factor 15, 4‐disulfide core domain protein 2, and kidney injury molecule were related to all of the 3 major CVD outcomes. A lasso selection of 11 proteins improved discrimination of incident CVD by 5.0% ( P =0.0038). Conclusions Large‐scale proteomics seem useful for the discovery of new risk markers for CVD and to improve risk prediction in an elderly population of men. Further studies are needed to replicate the findings in independent samples of both men and women of different ages.

2017 ◽  
Vol 77 (3) ◽  
pp. 386-392 ◽  
Author(s):  
Jeffrey R Curtis ◽  
Fenglong Xie ◽  
Lang Chen ◽  
Kenneth G Saag ◽  
Huifeng Yun ◽  
...  

BackgroundRheumatoid arthritis (RA) disease activity and associated systemic inflammation has been associated with serious infection (SIEs), myocardial infarction (MI) and coronary heart disease (CHD) events based on a few registry studies or clinical trials. There are few data from large-scale population-based studies given feasibility challenges in conducting such investigations.MethodsMultibiomarker disease activity (MBDA) test scores (n=77 641) were linked to Medicare for US patients with RA. Outcomes of interest were hospitalised pneumonia/sepsis (SIE), MI and a composite CHD outcome. The MBDA score ranges from 1 to 100 and was analysed as time-varying. Cox proportional hazards models evaluated the association between MBDA score and SIEs, MI and CHD events, controlling for potential confounders. A sensitivity analysis excluded C reactive protein (CRP) from the MBDA score.ResultsThere were 17 433 and 16 796 patients eligible for the SIE and MI/CHD analyses, respectively. Mean (SD) age was 69 (11) years, 79% were women, 81% were white and 38% were disabled. Over 16 424 person-years of follow-up, there were 452 SIE events, 132 MIs and 181 CHD events. Higher MBDA scores were associated with SIEs (HR=1.32, 95% CI 1.23 to 1.41 per 10 unit MBDA score change). For MI/CHD events, a threshold effect was present; higher disease activity by MBDA score was associated with increased MI (HR=1.52, 95% CI 0.92 to 2.49) and CHD rates (HR=1.54, 95% CI 1.01 to 2.34, comparing scores ≥30 vs <30). Analyses of the MBDA score without CRP yielded similar results.ConclusionHigher MBDA scores were associated with hospitalised infection, MI and CHD events in a large, predominantly older, US RA population.


2021 ◽  
Vol 8 ◽  
Author(s):  
Pei-Pei Zheng ◽  
Si-Min Yao ◽  
Di Guo ◽  
Ling-ling Cui ◽  
Guo-Bin Miao ◽  
...  

Background: The prevalence and prognostic value of heart failure (HF) stages among elderly hospitalized patients is unclear.Methods: We conducted a prospective, observational, multi-center, cohort study, including hospitalized patients with the sample size of 1,068; patients were age 65 years or more, able to cooperate with the assessment and to complete the echocardiogram. Two cardiologists classified all participants in various HF stages according to 2013 ACC/AHA HF staging guidelines. The outcome was rate of 1-year major adverse cardiovascular events (MACE). The Kaplan–Meier method and Cox proportional hazards models were used for survival analyses. Survival classification and regression tree analysis were used to determine the optimal cutoff of N-terminal pro-brain natriuretic peptide (NT-proBNP) to predict MACE.Results: Participants' mean age was 75.3 ± 6.88 years. Of them, 4.7% were healthy and without HF risk factors, 21.0% were stage A, 58.7% were stage B, and 15.6% were stage C/D. HF stages were associated with worsening 1-year survival without MACE (log-rank χ2 = 69.62, P &lt; 0.001). Deterioration from stage B to C/D was related to significant increases in HR (3.636, 95% CI, 2.174–6.098, P &lt; 0.001). Patients with NT-proBNP levels over 280.45 pg/mL in stage B (HR 2; 95% CI 1.112–3.597; P = 0.021) and 11,111.5 pg/ml in stage C/D (HR 2.603, 95% CI 1.014–6.682; P = 0.047) experienced a high incidence of MACE adjusted for age, sex, and glomerular filtration rate.Conclusions : HF stage B, rather than stage A, was most common in elderly inpatients. NT-proBNP may help predict MACE in stage B.Trial Registration: ChiCTR1800017204; 07/18/2018.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Yariv Gerber ◽  
Susan A Weston ◽  
Maurice E Sarano ◽  
Sheila M Manemann ◽  
Alanna M Chamberlain ◽  
...  

Background: Little is known about the association between coronary artery disease (CAD) and the risk of heart failure (HF) after myocardial infarction (MI), and whether it differs by reduced (HFrEF) or preserved (HFpEF) ejection fraction (EF) has yet to be determined. Subjects and Methods: Olmsted County, Minnesota residents (n=1,924; mean age, 64 years; 66% male) with first MI diagnosed in 1990-2010 and no prior HF were followed through 2013. Framingham Heart Study criteria were used to define HF, which was further classified according to EF (applying a 50% cutoff). The extent of angiographic CAD was defined at index MI according to the number of major epicardial coronary arteries with ≥50% lumen diameter obstruction. Fine & Gray and Cox proportional hazards regression models were used to assess the association of CAD categories with incidence of HF, and multiple imputation methodology was applied to account for the 19% with missing EF data. Results: During a mean (SD) follow-up of 6.7 (5.9) years, 594 patients developed HF. Adjusted for age and sex, with death considered a competing risk, the cumulative incidence rates of HF among patients with 1- (n=581), 2- (n=622), and 3-vessel disease (n=721) were 11.2%, 14.6% and 20.5% at 30 days; and 18.1%, 22.3% and 29.4% at 5 years after MI, respectively. The increased risk of HF with greater number of occluded vessels was only modestly attenuated after further adjustment for patient and MI characteristics, and did not differ materially by EF (Table). Conclusions: The extent of angiographic CAD expressed by the number of diseased vessels is independently associated with HF incidence after MI. The association is evident promptly after MI and applies to both HFrEF and HFpEF.


Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Faye L Norby ◽  
Lindsay G Bengtson ◽  
Lin Y Chen ◽  
Richard F MacLehose ◽  
Pamela L Lutsey ◽  
...  

Background: Rivaroxaban is a novel oral anticoagulant approved in the US in 2011 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Information on risks and benefits among rivaroxaban users in real-world populations is limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases between 2010 and 2013. We selected patients with a history of NVAF and initiating rivaroxaban or warfarin. Rivaroxaban users were matched with up to 5 warfarin users by age, sex, database enrollment date and drug initiation date. Ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding outcomes were defined by ICD-9-CM codes in an inpatient claim after drug initiation date. Cox proportional hazards models were used to assess the association between rivaroxaban vs. warfarin use and outcomes adjusting for age, sex, and CHA2DS2-VASc score. Separate models were used to compare a) new rivaroxaban users with new warfarin users, and b) switchers from warfarin to rivaroxaban to continuous warfarin users. Results: Our analysis included 34,998 rivaroxaban users matched to 102,480 warfarin users with NVAF (39% female, mean age 71), in which 487 ischemic strokes, 179 ICB, 647 MI, and 1353 GI bleeds were identified during a mean follow-up of 9 months. Associations of rivaroxaban vs warfarin were similar in new users and switchers; therefore we pooled both analyses. Rivaroxaban users had lower rates of ICB (hazard ratio (HR) (95% confidence interval (CI)) = 0.72 (0.46, 1.12))) and ischemic stroke (HR (95% CI) = 0.88 (0.68, 1.13)), but higher rates of GI bleeding (HR (95% CI) = 1.15 (1.01, 1.33)) when compared to warfarin users (table). Conclusion: In this large population-based study of NVAF patients, rivaroxaban users had a non-significant lower risk of ICB and ischemic stroke than warfarin users, but a higher risk of GI bleeding. These real-world findings are comparable to results reported in published clinical trials.


Author(s):  
Nitin Goyal ◽  
Daniel D. Bohl ◽  
Robert W. Wysocki

Abstract Introduction Our purposes were to (1) characterize the timeline of eight postoperative complications following hand surgery, (2) assess complication timing for the procedures that account for the majority of adverse events, and (3) determine any differences in complication timing between outpatient and inpatient procedures. Materials and Methods Patients undergoing hand, wrist, and forearm procedures from 2005 to 2016 were identified in the National Surgical Quality Improvement Program database. Timing of eight adverse events was characterized. Cox proportional hazards modeling was used to compare adverse event timing between inpatient and outpatient procedures. Results A total of 59,040 patients were included. The median postoperative day of diagnosis for each adverse event was as follows: myocardial infarction 1, pulmonary embolism 2, acute kidney injury 3, pneumonia 8, deep vein thrombosis 9, sepsis 13, urinary tract infection 15, and surgical site infection 16. Amputations, fasciotomies, and distal radius open reduction internal fixation accounted for the majority of adverse events. Complication timing was significantly earlier in inpatients compared with outpatients for myocardial infarction. Conclusion This study characterizes postoperative adverse event timing following hand surgery. Surgeons should have the lowest threshold for testing for each complication during the time period of greatest risk. Level of Evidence This is a therapeutic, Level III study.


2020 ◽  
Author(s):  
Yingting Zuo ◽  
Anxin Wang ◽  
Shuohua Chen ◽  
Xue Tian ◽  
Shouling Wu ◽  
...  

Abstract Background The relationship between estimated glomerular filtration rate (eGFR) trajectories and myocardial infarction (MI) remains unclear in people with diabetes or prediabetes. We aimed to identify common eGFR trajectories in people with diabetes or prediabetes and to examine their association with MI risk. Methods The data of this analysis was derived from the Kailuan study, which was a prospective community-based cohort study. The eGFR trajectories of 24,723 participants from year 2006 to 2012 were generated by latent mixture modeling. Incident cases of MI occurred during 2012 to 2017, confirmed by review of medical records. Cox proportional hazards models were used to calculate hazard ratios (HR) and their 95% confidence intervals (CIs) for the subsequent risk of MI of different eGFR trajectories. Results We identified 5 distinct eGFR trajectories, and named them as low-stable (9.4%), moderate-stable (31.4%), moderate-increasing (29.5%), high-decreasing (13.9%) and high-stable (15.8%) according to their range and pattern. During a mean follow-up of 4.61 years, there were a total of 235 incident MI. Although, the high-decreasing group had similar eGFR levels with the moderate-stable group at last exposure period, the risk was much higher (adjusted HR, 3.43; 95%CI, 1.56–7.54 versus adjusted HR, 2.82; 95%CI, 1.34–5.95). Notably, the moderate-increasing group had reached to the normal range, still had a significantly increased risk (adjusted HR, 2.55; 95%CI, 1.21–5.39). Conclusions eGFR trajectories were associated with MI risk in people with diabetes or prediabetes. Emphasis should be placed on early and long-term detection and control of eGFR decreases to further reduce MI risk.


2021 ◽  
Vol 8 ◽  
Author(s):  
Qiu-hong Tan ◽  
Lin Liu ◽  
Yu-qing Huang ◽  
Yu-ling Yu ◽  
Jia-yi Huang ◽  
...  

Background: Limited studies focused on the association between serum uric acid (SUA) change with ischemic stroke, and their results remain controversial. The present study aimed to investigate the relationship between change in SUA with ischemic stroke among hypertensive patients.Method: This was a retrospective cohort study. We recruited adult hypertensive patients who had two consecutive measurements of SUA levels from 2013 to 2014 and reported no history of stroke. Change in SUA was assessed as SUA concentration measured in 2014 minus SUA concentration in 2013. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan–Meier analysis and log-rank test were performed to quantify the difference in cumulative event rate. Additionally, subgroup analysis and interaction tests were conducted to investigate heterogeneity.Results: A total of 4,628 hypertensive patients were included, and 93 cases of ischemic stroke occurred during the mean follow-up time of 3.14 years. Participants were categorized into three groups according to their SUA change tertiles [low (SUA decrease substantially): &lt;-32.6 μmol/L; middle (SUA stable): ≥-32.6 μmol/L, &lt;40.2 μmol/L; high (SUA increase substantially): ≥40.2 μmol/L]. In the fully adjusted model, setting the SUA stable group as reference, participants in the SUA increase substantially group had a significantly elevated risk of ischemic stroke [HR (95% CI), 1.76 (1.01, 3.06), P = 0.0451], but for the SUA decrease substantially group, the hazard effect was insignificant [HR (95% CI), 1.31 (0.75, 2.28), P = 0.3353]. Age played an interactive role in the relationship between SUA change and ischemic stroke. Younger participants (age &lt; 65 years) tended to have a higher risk of ischemic stroke when SUA increase substantially.Conclusion: SUA increase substantially was significantly correlated with an elevated risk of ischemic stroke among patients with hypertension.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xin He ◽  
Jingjing Zhao ◽  
Jiangui He ◽  
Yugang Dong ◽  
Chen Liu

Abstract Background Secondhand smoke (SHS) exposure is a well-established cardiovascular risk factor, yet association between SHS and prognosis of heart failure remains uncertain. Method Data were obtained from the US National Health and Nutrition Examination Surveys III from 1988 to 1994. Currently nonsmoking adults with a self-reported history of heart failure were included. Household SHS exposure was assessed by questionnaire. Participants were followed up through December 31, 2011. Cox proportional-hazards models were used to assess the association of household SHS exposure and mortality risk. Potential confounding factors were adjusted. Results Of 572 currently nonsmoking patients with heart failure, 88 were exposed to household SHS while 484 were not. There were totally 475 deaths during follow-up. In univariate analysis, household SHS was not associated with mortality risk (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.76–1.26, p = 0.864). However, after adjustment for demographic variables, socioeconomic variables and medication, heart failure patients in exposed group had a 43% increase of mortality risk compared with those in unexposed group (HR: 1.43, 95% CI: 1.10–1.86, p = 0.007). Analysis with further adjustment for general health status and comorbidities yielded similar result (HR: 1.47, 95% CI: 1.13–1.92, p = 0.005). Conclusion Household SHS exposure was associated with increased mortality risk in heart failure patients.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Matthew A Mercuri ◽  
Alexander E Merkler ◽  
Neal S Parikh ◽  
Michael E Reznik ◽  
Hooman Kamel

Background: Vascular brain injury can result in epilepsy. It is posited that seizures in elderly patients might reflect subclinical vascular disease and thus herald future clinical vascular events. Hypothesis: Seizures in elderly patients are associated with an increased risk of ischemic stroke or myocardial infarction (MI). Methods: We obtained inpatient and outpatient claims data from 2008-2014 on a 5% sample of Medicare beneficiaries ≥66 years of age. The predictor variable was epilepsy, defined as two or more inpatient or outpatient claims with a diagnosis of seizure. The primary outcome was a composite of ischemic stroke or acute MI. The predictors and outcomes were all ascertained with previously validated ICD-9-CM code algorithms. Survival statistics and Cox proportional hazards models were used to assess the relationship between epilepsy and incident ischemic stroke or MI while adjusting for demographic characteristics and vascular risk factors. Patients were censored at the first occurrence of a stroke or MI, at the time of death, or on December 31, 2014. Results: Among 1,548,556 beneficiaries with a mean follow-up of 4.4 (±1.8) years, 15,055 (1.0%) developed epilepsy and 121,866 (7.9%) experienced an ischemic stroke or acute MI. Patients with seizures were older (76.1 versus 73.7 years) and had a significantly higher burden of vascular comorbidities than the remainder of the cohort. The annual incidence of stroke or acute MI was 3.28% (95% confidence interval [CI], 3.10-3.47%) in those with seizures versus 1.79% (95% CI, 1.78-1.80%) in those without (unadjusted hazard ratio [HR], 1.89; 95% CI, 1.78-2.00). After adjustment for demographics and risk factors, epilepsy had a weak association with the composite outcome (adjusted HR, 1.36; 95% CI, 1.29-1.44), a stronger association with ischemic stroke (adjusted HR, 1.77; 95% CI, 1.65-1.90), and no association with acute MI (adjusted HR, 0.95; 95% CI, 0.86-1.04). Conclusions: We found an association between epilepsy in elderly patients and future ischemic stroke but not acute MI. Therefore, seizures might signify occult cerebrovascular disease but not necessarily occult disease in other vascular beds.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Nada El Husseini ◽  
Gregg C Fonarow ◽  
Eric E Smith ◽  
Christine Ju ◽  
Lee H Schwamm ◽  
...  

Background: The extent to which CKD is associated with 30-day and 1-year post ischemic stroke mortality and rehospitalization rates has not been well studied. Methods: Data from 232,236 fee for service Medicare patients admitted with ischemic stroke to 1581 AHA GWTG-Stroke participating hospitals between January 2009 and December 2012 were analyzed. Estimated GFR in mL/min/1.73 m2 was determined based on the MDRD study equation categorized as: no CKD (GFR ≥60); stage 3a CKD (GFR 45-59); stage 3b CKD (GFR 30-44); stage 4 CKD, (GFR 15-29); stage 5 CKD (GFR <15 excluding those on dialysis). Dialysis was identified by ICD-9 codes. Multivariable Cox proportional hazards models adjusted for demographics, medical history, NIHSS, arrival hour, and hospital characteristics were used to determine the independent associations of CKD (reference group those without CKD) with mortality and readmission at 30 days and 1 year. Results: After adjustment, 30-days poststroke mortality was highest among those with CKD stage 5 (HR 1.94, 95%CI 1.72-2.18), even after excluding in-hospital mortality and patients discharged to hospice (HR 2.09, 95%CI 1.66-2.63). Unadjusted 1-year mortality and readmission rates were highest among patients on dialysis (Figure). After adjustment, 1-year post-stroke mortality remained highest among patients on dialysis (HR 2.19, 95%CI 2.08-2.31), even after excluding in-hospital mortality and discharge to hospice (HR 2.65, 95%CI 2.49-2.81). For those discharged alive, 30-day and 1-year rehospitalization rates were also highest among patients on dialysis (HR 2.10, 95%CI 1.95-2.26; HR 2.55, 95%CI 2.44-2.66, respectively) as was the 30-day and 1-year composite of mortality and rehospitalization (HR 2.04, 95%CI 1.90-2.18; HR 2.46, 95% CI 2.36-2.56, respectively). Conclusion: Among Medicare beneficiaries with acute ischemic stroke, poststroke mortality and rehospitalization varied by CKD stage and were highest among those with advanced CKD.


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