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Identification of Haptoglobin as a Potential Biomarker in Young Adults with Acute Myocardial Infarction by Proteomic Analysis.

ABSTRACT: Background:Acute myocardial infarction (AMI) molecular research in young adults is still limited. The aim of this study is to identify AMI proteomic biomarker(s) in young adults. Methods:This study comprised of two phases namely discovery and verification. In the discovery phase, proteins in the pooled plasma samples from young male adults between 18 and 45 years (10 AMI patients and 10 controls) were separated using two-dimensional electrophoresis. The protein spots that were expressed differently in the AMI patients were identified via matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. The plasma concentrations of these proteins were quantified using enzyme-linked immunosorbent assay during the verification phase (40 AMI patients and 80 controls). Results:Haptoglobin (Hp), apolipoprotein AI (Apo AI) and apolipoprotein AIV (Apo AIV) were up-regulated in the discovery phase. In the verification phase, the plasma concentration of Hp was significantly higher in AMI patients than the controls (P < 0.001). Logistic regression showed an association between Hp and AMI in young adults (odds ratio [OR] = 1.016, 95% CI: 1.002-1.030, P = 0.025) independent of other AMI risk factors. Hp was significantly correlated with high sensitivity C-reactive protein (hs-CRP) (r = 0.424, P < 0.001). Conclusion:In young adults with AMI, plasma Hp concentrations were elevated and it is independently associated with AMI. A positive correlation with hs-CRP suggests Hp could be a potential biomarker of AMI in young adults.

SUBMITTER: Mohamed Bakrim N

PROVIDER: S-EPMC7409576 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Identification of Haptoglobin as a Potential Biomarker in Young Adults with Acute Myocardial Infarction by Proteomic Analysis.

Mohamed Bakrim Norbaiyah N Mohd Shah Aida Nur Sharini ANS Talib Norlelawati A NA Ab Rahman Jamalludin J Abdullah Aszrin A

The Malaysian journal of medical sciences : MJMS 20200301 2

<h4>Background</h4>Acute myocardial infarction (AMI) molecular research in young adults is still limited. The aim of this study is to identify AMI proteomic biomarker(s) in young adults.<h4>Methods</h4>This study comprised of two phases namely discovery and verification. In the discovery phase, proteins in the pooled plasma samples from young male adults between 18 and 45 years (10 AMI patients and 10 controls) were separated using two-dimensional electrophoresis. The protein spots that were exp ...[more]

PMID: 32788843

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Project description:ImportanceAn increasing proportion of people in the US hospitalized for acute myocardial infarction (AMI) are younger than 55 years, with the largest increase in young women. Effective prevention requires an understanding of risk factors associated with risk of AMI in young women compared with men.ObjectivesTo assess the sex-specific associations of demographic, clinical, and psychosocial risk factors with first AMI among adults younger than 55 years, overall, and by AMI subtype.Design, setting, and participantsThis study used a case-control design with 2264 patients with AMI, aged 18 to 55 years, from the VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) study and 2264 population-based controls matched for age, sex, and race and ethnicity from the National Health and Nutrition Examination Survey from 2008 to 2012. Data were analyzed from April 2020 to November 2021.ExposuresA wide range of demographic, clinical, and psychosocial risk factors.Main outcomes and measuresOdds ratios (ORs) and population attributable fractions (PAF) for first AMI associated with demographic, clinical, and psychosocial risk factors.ResultsOf the 4528 case patients and matched controls, 3122 (68.9%) were women, and the median (IQR) age was 48 (44-52) years. Seven risk factors (diabetes [OR, 3.59 (95% CI, 2.72-4.74) in women vs 1.76 (1.19-2.60) in men], depression [OR, 3.09 (95% CI, 2.37-4.04) in women vs 1.77 (1.15-2.73) in men], hypertension [OR, 2.87 (95% CI, 2.31-3.57) in women vs 2.19 (1.65-2.90) in men], current smoking [OR, 3.28 (95% CI, 2.65-4.07) in women vs 3.28 (2.65-4.07) in men], family history of premature myocardial infarction [OR, 1.48 (95% CI, 1.17-1.88) in women vs 2.42 (1.71-3.41) in men], low household income [OR, 1.79 (95% CI, 1.28-2.50) in women vs 1.35 (0.82-2.23) in men], hypercholesterolemia [OR, 1.02 (95% CI, 0.81-1.29) in women vs 2.16 (1.49-3.15) in men]) collectively accounted for the majority of the total risk of AMI in women (83.9%) and men (85.1%). There were significant sex differences in risk factor associations: hypertension, depression, diabetes, current smoking, and family history of diabetes had stronger associations with AMI in young women, whereas hypercholesterolemia had a stronger association in young men. Risk factor profiles varied by AMI subtype, and traditional cardiovascular risk factors had higher prevalence and stronger ORs for type 1 AMI compared with other AMI subtypes.Conclusions and relevanceIn this case-control study, 7 risk factors, many potentially modifiable, accounted for 85% of the risk of first AMI in young women and men. Significant differences in risk factor profiles and risk factor associations existed by sex and by AMI subtype. These findings suggest the need for sex-specific strategies in risk factor modification and prevention of AMI in young adults. Further research is needed to improve risk assessment of AMI subtypes.

Project description:BACKGROUND:Sex differences are known to exist in the management of older patients presenting with acute myocardial infarction (AMI). Few studies have examined the incidence and risk factors of AMI among young patients, or whether clinical management differs by sex. METHODS:The Atherosclerosis Risk in Communities (ARIC) Surveillance study conducts hospital surveillance of AMI in 4 US communities (MD, MN, MS, and NC). AMI was classified by physician review, using a validated algorithm. Medications and procedures were abstracted from the medical record. Our study population was limited to young patients aged 35 to 54 years. RESULTS:From 1995 to 2014, 28?732 weighted hospitalizations for AMI were sampled among patients aged 35 to 74 years. Of these, 8737 (30%) were young. The annual incidence of AMI hospitalizations increased for young women but decreased for young men. The overall proportion of AMI admissions attributable to young patients steadily increased, from 27% in 1995 to 1999 to 32% in 2010 to 2014 ( P for trend=0.002), with the largest increase observed in young women. History of hypertension (59% to 73%, P for trend<0.0001) and diabetes mellitus (25% to 35%, P for trend<0.0001) also increased among young AMI patients. Compared to young men, young women presenting with AMI were more often black and had a greater comorbidity burden. In adjusted analyses, young women had a lower probability of receiving lipid-lowering therapies (relative risk [RR]=0.87; 95% confidence interval [CI], 0.80-0.94), nonaspirin antiplatelets (RR=0.83; 95% CI, 0.75-0.91), beta blockers (RR=0.96; 95% CI, 0.91-0.99), coronary angiography (RR=0.93; 95% CI, 0.86-0.99) and coronary revascularization (RR = 0.79; 95% CI, 0.71-0.87). However, 1-year all-cause mortality was comparable for women versus men (HR=1.10; 95% CI, 0.83-1.45). CONCLUSIONS:The proportion of AMI hospitalizations attributable to young patients increased from 1995 to 2014 and was especially pronounced among women. History of hypertension and diabetes among young patients admitted with AMI increased over time as well. Compared with young men, young women presenting with AMI had a lower likelihood of receiving guideline-based AMI therapies. A better understanding of factors underlying these changes is needed to improve care of young patients with AMI.

Project description:Background Stress experienced in a marriage or committed relationship may be associated with worse patient-reported outcomes after acute myocardial infarction (AMI), but little is known about this association in young adults (≤55 years) with AMI. Methods and Results We used data from VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), an observational cohort study that enrolled individuals aged 18 to 55 years with AMI (2008-2012). Marital stress was self-reported 1 month after AMI using the Stockholm Marital Stress Scale (categorized as absent/mild, moderate, and severe). Outcomes were physical/mental health (Short Form-12), generic health status (EuroQol-5 Dimensions), cardiac-specific quality of life and angina (Seattle Angina Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and all-cause readmission 1 year after AMI. Regression models were sequentially adjusted for baseline health, demographics (sex, age, race or ethnicity), and socioeconomic factors (education, income, employment, and insurance). Sex and marital stress interaction was also tested. Among 1593 married/partnered participants, 576 (36.2%) reported severe marital stress, which was more common in female than male participants (39.4% versus 30.4%, P=0.001). Severe marital stress was significantly associated with worse mental health (beta=-2.13, SE=0.75, P=0.004), generic health status (beta=-3.87, SE=1.46, P=0.008), cardiac-specific quality of life (beta=-6.41, SE=1.65, P<0.001), and greater odds of angina (odds ratio [OR], 1.49 [95% CI, 1.06-2.10], P=0.023) and all-cause readmissions (OR, 1.45 [95% CI, 1.04-2.00], P=0.006), after adjusting for baseline health, demographics, and socioeconomic factors. These associations were similar across sexes (P-interaction all >0.05). Conclusions The association between marital stress and worse 1-year health outcomes was statistically significant in young patients with AMI, suggesting a need for routine screening and the creation of interventions to support patients with stress recovering from an AMI.

Project description:Screening for specific biomarkers of early-stage detection of ovarian cancer is a major health priority due to the asymptomatic nature and poor survival characteristic of the disease. We utilised two-dimensional gel electrophoresis (2DE) to identify differentially expressed proteins in the serum of ovarian cancer patients that may be useful as biomarkers of this disease. In this study, 38 ovarian cancer patients at different pathological grades (grade 1 (n=6), grade 2 (n=8) and grade 3 (n=24)) were compared to a control group of eight healthy women. Serum samples were treated with a mixture of Affigel-Blue and protein A (5 : 1) for 1 h to remove high abundance protein (e.g. immunoglobulin and albumin) and were displayed using 11 cm, pH 4-7 isoelectric focusing strips for the first dimension and 10% acrylamide gel electrophoresis for the second dimension. Protein spots were visualised by SYPRO-Ruby staining, imaged by FX-imager and compared and analysed by PDQuest software. A total of 24 serum proteins were differentially expressed in grade 1 (P<0.05), 31 in grade 2 (P<0.05) and 25 in grade 3 (P<0.05) ovarian cancer patients. Six of the protein spots that were significantly upregulated in all groups of ovarian cancer patients were identified by nano-electrospray quadrupole quadrupole time-of-flight mass spectrometry (n-ESIQ(q)TOFMS) and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOFMS) as isoforms of haptoglobin-1 precursor (HAP1), a liver glycoprotein present in human serum. Further identification of the spots at different pathological grades was confirmed by Western blotting using monoclonal antibody against a haptoglobin epitope contained within HAP1. Immunohistochemical localisation of HAP1-like activity was present in malignant ovarian epithelium and stroma but strong immunostaining was present in blood vessels, areas with myxomatous stroma and vascular spaces. No tissue localisation of HAP1-like immunoreactivity was observed in normal ovarian surface epithelium. These data highlight the need to assess circulating concentration of HAP1 in the serum of ovarian cancer patients and evaluate its potential as a biomarker in the early diagnosis of ovarian cancer.

Project description:BACKGROUND:Substance abuse is increasingly prevalent among young adults, but data on cardiovascular outcomes remain limited. OBJECTIVES:The objectives of this study were to assess the prevalence of cocaine and marijuana use in adults with their first myocardial infarction (MI) at ≤50 years and to determine its association with long-term outcomes. METHODS:The study retrospectively analyzed records of patients presenting with a type 1 MI at ≤50 years at 2 academic hospitals from 2000 to 2016. Substance abuse was determined by review of records for either patient-reported substance abuse during the week before MI or substance detection on toxicology screen. Vital status was identified by the Social Security Administration's Death Master File. Cause of death was adjudicated using electronic health records and death certificates. Cox modeling was performed for survival free from all-cause and cardiovascular death. RESULTS:A total of 2,097 patients had type 1 MI (mean age 44.0 ± 5.1 years, 19.3% female, 73% white), with median follow-up of 11.2 years (interquartile range: 7.3 to 14.2 years). Use of cocaine and/or marijuana was present in 224 (10.7%) patients; cocaine in 99 (4.7%) patients, and marijuana in 125 (6.0%). Individuals with substance use had significantly lower rates of diabetes (14.7% vs. 20.4%; p = 0.05) and hyperlipidemia (45.7% vs. 60.8%; p < 0.001), but they were significantly more likely to use tobacco (70.3% vs. 49.1%; p < 0.001). The use of cocaine and/or marijuana was associated with significantly higher cardiovascular mortality (hazard ratio: 2.22; 95% confidence interval: 1.27 to 3.70; p = 0.005) and all-cause mortality (hazard ratio: 1.99; 95% confidence interval: 1.35 to 2.97; p = 0.001) after adjusting for baseline covariates. CONCLUSIONS:Cocaine and/or marijuana use is present in 10% of patients with an MI at age ≤50 years and is associated with worse all-cause and cardiovascular mortality. These findings reinforce current recommendations for substance use screening among young adults with an MI, and they highlight the need for counseling to prevent future adverse events.

Project description:BackgroundHaptoglobin (Hp) is an abundant plasma protein with anti-oxidant properties. Hp polymorphism is associated with cardio-metabolic dysfunction but the allele conferring risk of developing acute myocardial infarction (AMI) in type 2 diabetes (T2D) patients is unclear. This study aimed to investigate the association of Hp phenotype (Hp 1-1, 2-1 and 2-2) with incident AMI in Chinese T2D patients.MethodsThis prospective study included Chinese T2D participants from the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D) and Diabetic Nephropathy (DN) cohorts. Information on incidence of non-fatal AMI was collected by data linkage with the Singapore Myocardial Infarction Registry. Hp phenotype was determined using enzyme-linked immunosorbent assay. Cox proportional hazards regression models were used to evaluate the association of Hp phenotype with incident AMI, adjusted for traditional risk factors separately in two cohorts, then meta-analysed.ResultsIn total, 2324 Chinese participants (SMART2D; N = 1034, mean age [SD] of 59 [11]) and (DN: N = 1290, mean age [SD] of 58 [12]) were included in this study. There were total of 30 (56 events per 10,000 patient-years) and 99 (128 events per 10,000 patient-years) AMI events in SMART2D and DN cohorts respectively. In meta-analysis, presence of Hp 1 allele conferred 43% (hazard ratio [HR] = 1.43 [95% CI 1.10-1.87], P = 0.008, Phet = 0.413) increased risk of incident AMI, independent of age, sex, smoking, body mass index, HbA1c, diabetes duration, lipids, hypertension, renal function and usage of insulin and RAS antagonist. In adjusted model, compared to Hp 2-2 groups, individuals with Hp 1-1 (HR = 2.18 [95% CI 1.19-3.76], P = 0.010, Phet = 0.193) and Hp 2-1 (HR = 1.45 [95% CI 0.98-2.14], P = 0.065, Phet = 0.576) were at a higher risk of incident AMI. Moreover, compared to Hp 2-2 groups, non-Hp 2-2 groups (Hp 1-1 and Hp 2-1) were at 55% increased risk of incident AMI (HR = 1.55 [95% CI 1.07-2.24], P = 0.021, Phet = 0.940).ConclusionsHp 1-1 phenotype was associated with increased risk of incident AMI, independent of traditional risk factors, in Chinese patients with T2D. Hp phenotyping may allow for identification of T2D individuals at higher risk for onset of AMI. However, further studies are needed to understand the underlying mechanism between Hp alleles and risk for AMI.

Dataset Information

Identification of Haptoglobin as a Potential Biomarker in Young Adults with Acute Myocardial Infarction by Proteomic Analysis.

Publications

Identification of Haptoglobin as a Potential Biomarker in Young Adults with Acute Myocardial Infarction by Proteomic Analysis.

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