Healthy Population Cohort Research Articles

Remarkable temporal stability of high‐abundance human plasma proteins assessed by targeted mass spectrometry

To examine temporal fluctuations in selected plasma protein levels over a period of nearly 4 months and assess biological variation of these proteins across a healthy population cohort. Plasma was collected from ten healthy volunteers over two time-courses: (i) weekly for 4 weeks; (ii) bimonthly over 4 months and depleted of albumin and IgG. SRM MS was used to determine the relative quantitation of 31 plasma proteins commonly observed in biomarker studies over these time courses. Estimates of between-subject and within-subject biological variances determined by SRM were calculated for each protein. Replicate analysis demonstrated the high precision of SRM assays of plasma proteins. Statistical analysis indicated that none of the measured proteins exhibited significant temporal fluctuations over either time course. Overall, time-based intraindividual quantitative variation of plasma protein levels was considerably lower than biological variation occurring between individual volunteers. This study is the first to show robust temporal stability of the plasma proteome in healthy individuals using SRM-based peptide quantitation. This is important as it provides a strong basis for reliable detection of disease/treatment-related changes of these plasma proteins and others using SRM.

Prostate cancer screening in a Saudi population: an explanatory trial study

The aim of this study is to explore the actual situation of prostate cancer in a cohort of healthy population in Saudi Arabia and to show the feasibility of screening for this disease using the internationally agreed criteria. This study was conducted in the city of Riyadh, in the outpatient clinics of four different health facilities. All men presented to the outpatient clinics during the period of study, from January 2008 to December 2008, were invited to participate in the study, in which they were subjected to PSA blood testing and digital rectal examination (DRE). When either test was abnormal, transrectal ultrasound and multiple prostatic biopsies were performed for confirmation of the results. A total of 2100 healthy males who met the inclusion criteria of the study were evaluated. The highest percentage of men with PSA>/=4 ng ml(-1) was in the age group 61-70, 51-60 years (42.7 and 31.8%, respectively). The number of subjects with an elevated PSA only was 172 (8.1%). Those having both elevated PSA and an abnormal DRE were 51 (2.4%). The total number referred to biopsy was 223. Fifty two subjects had a positive diagnosis of prostatic adenocarcinoma, which compromised 2.5% of the cohort studied. The cancer in 27 (52%) persons was organ confined, whereas in 14 (26.9%), it was metastatic. The prevalence rate of prostate cancer detected by screening was higher than expected and the disease was advanced. Larger community-based larger studies are highly warranted specially among high-risk groups.

Higher sensitivity troponin assays: Quo vadis?

Central to the universal definition of myocardial infarction (MI) is the recommendation that cardiac troponin (cTn; I or T) is the biomarker of choice for detection of myocardial necrosis because of its high clinical sensitivity and almost absolute myocardial tissue specificity.1 The guidelines are based on the assays presently available for clinical use. However, predicated on data suggesting that there is additional information below the levels that are presently being measured, manufacturers have begun to develop much more sensitive cTn assays that allow measurement of concentrations in the range of pg/ml rather than ng/ml. These assays should permit accurate measurement of most if not all normal subjects with an optimal level of analytical imprecision (coefficient of variation ≤10%). Preliminary observations using levels now measurable and based on values below the present 99th percentile of the current assays suggest that more sensitive assays will result in an increased diagnosis of MI and that these patients are at substantial risk post-infarction.2 Recent data indicate that these previously undetectable levels are also associated with worse outcomes in patients with an acute coronary syndrome,2 especially if these low level elevations continue post-event,3 in those with heart failure,4 and stable angina pectoris,5 and even elderly apparently healthy population cohorts.6,7 These concentrations have also been found to be associated with cardiovascular high-risk features, higher carotid artery plaque burden, and … *Corresponding author. Tel: +45 89497614, Fax: +45 89497619, Email: Kristian.Thygesen{at}as.aaa.dk; or kthygesen{at}oncable.dk

Coagulation factors, activation markers and risk of coronary heart disease: the Northwick Park Heart Studies.

Coagulation factors, activation markers and risk of coronary heart disease: the Northwick Park Heart Studies.

Predictive value of high sensitivity CRP in patients with diastolic heart failure

Background C-reactive protein (CRP) has been tested in patients with systolic heart failure (HF) and mixed results have been obtained with regards to its potential predictive value. However, the role of C-reactive protein (CRP) in patients with diastolic HF is not established. We studied the predictive role of high sensitivity CRP (hsCRP) in patients with diastolic HF. Methods HsCRP levels were measured in a cohort of CHF outpatients, 77 patients with diastolic HF and 217 patients with systolic HF. Concentrations were compared to a large cohort of healthy population ( n = 7701) and associated with the HF admissions and mortality of the patients. Results Levels of hsCRP did not differ between patients with systolic and diastolic HF and were significantly elevated compared to the cohort of healthy subjects even after adjustment to various clinical parameters ( p < 0.0001). In patients with diastolic HF, hsCRP levels associated with New York Heart Association functional class (NYHA-FC) ( r = 0.31 p = 0.01). On univariate Cox regression model hsCRP levels independently predicted hospitalizations in patients with systolic but not diastolic HF ( p = 0.047). Conclusion HsCRP concentrations are elevated in patients with diastolic HF and correlate with disease severity; their prognostic value in this patient population should be further investigated.

The Impact of Abnormalities in IGF and Inflammatory Systems on the Metabolic Syndrome

Low plasma levels of IGF-I, particularly when coupled with low levels of the potentially inhibitory IGF binding protein (IGFBP)-1 and higher levels of C-reactive protein (CRP), have been implicated in the pathogenesis of metabolic syndrome X and cardiovascular disease. We report the relative contributions of IGFBP-1 and CRP to the occurrence of the metabolic syndrome in a healthy population cohort to establish the extent to which these factors may contribute to subsequent risk of cardiovascular disease. The volunteers in the study were all participants in the Ely study, a continuing population-based cohort in Ely, Cambridgeshire, U.K. Of 839 individuals studied, 154 (18.4%) fulfilled criteria for the metabolic syndrome. Subjects with the metabolic syndrome had lower IGFBP-1 (14.4 microg/l [95% CI 12.9-16.0] vs. 25.4 [24.1-26.7], P < 0.001) and higher CRP (1.9 mg/l [1.6-2.2] vs. 1.0 [0.9-1.1], P < 0.001). Logistic regression, adjusted for age, sex, fasting insulin, and IGF-I, demonstrated a striking 14-fold increased risk for the metabolic syndrome (odds ratio 14.1 [4.1-48.4], P < 0.001) in individuals with a CRP value in the highest tertile and IGFBP-1 levels below the median. The combination of a high CRP concentration coupled with a low IGFBP-1 results in a dramatic increase in an individual's risk of having the metabolic syndrome. Further elucidation of the biological processes linking the IGF and inflammatory systems may allow the identification of novel therapeutic targets for cardiovascular risk reduction.

Seroepidemiology of human group C rotavirus in South Africa.

Sera from three separate healthy population cohorts were used to determine the incidence of group C rotavirus infections in 1,356 South Africans. Using an enzyme-linked immunosorbent assay based on a recombinant group C rotavirus VP6 protein, the total percent positivity was found to be 34.4% (range, 33 to 38%), with almost half of the population infected after the age of 20 years.