| 1. |
- Annborn, Martin, et al.
(author)
-
Procalcitonin after cardiac arrest - An indicator of severity of illness, ischemia-reperfusion injury and outcome.
- 2013
-
In: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 84:6, s. 782-787
-
Journal article (peer-reviewed)abstract
- AIM: To investigate serial serum concentrations of procalcitonin (PCT) and C-reactive protein (CRP) in patients treated with mild hypothermia after cardiac arrest, and to study their association to severe infections, post cardiac arrest syndrome (PCAS) and long-term outcome. METHODS: Serum samples from cardiac arrest patients treated with mild hypothermia were collected serially at admission, 2, 6, 12, 24, 36, 48 and 72h after cardiac arrest. PCT and CRP concentrations were determined and tested for association with three definitions of infection, two surrogate markers of PCAS (circulation-SOFA and time to return of spontaneous circulation (ROSC)) and cerebral performance category (CPC) at six months. RESULTS: Eighty-four patients were included. PCT displayed an earlier release pattern than CRP with a significant increase within 2h, increasing further at 6h and onwards in patients with poor outcome. CRP increased later and continued to rise during the study period. PCT was strongly associated with circulation-SOFA and time to ROSC, and predicted a poor neurologic outcome with high accuracy (area under the receiver operating characteristic curve of 0.88, 0.86 and 0.87 at 12, 24 and 48h respectively). No association of PCT or CRP to infection was observed. CONCLUSION: Our results suggest that PCT is released early after resuscitation following cardiac arrest, is associated with markers of PCAS but not with infection, and is an accurate predictor of poor outcome. Validation of these findings in larger studies is warranted.
|
|
| 2. |
- Annborn, Martin, et al.
(author)
-
The Combination of Biomarkers for Prognostication of Long-Term Outcome in Patients Treated with Mild Hypothermia After Out-of-Hospital Cardiac Arrest-A Pilot Study
- 2016
-
In: Therapeutic hypothermia and temperature management. - : Mary Ann Liebert Inc. - 2153-7933 .- 2153-7658. ; 6:2, s. 85-90
-
Journal article (peer-reviewed)abstract
- To explore if the brain biomarker neuron-specific enolase (NSE) in combination with a biomarker for stress; CT-proAVP (copeptin), oxidation; peroxiredoxin 4 (Prx4), inflammation; procalcitonin (PCT), or with biomarkers from the heart; midregional proatrial natriuretic peptide (MR-proANP), or troponin T (TnT) can improve the prognostic accuracy of long-term outcome after out-of-hospital cardiac arrest (OHCA). Serum samples from cardiac arrest patients, treated at 33°C for 24 hours, were collected serially at 12, 24, and 48 hours after cardiac arrest. The concentration of the investigated biomarkers was measured using stored samples, and long-term outcome was evaluated by the cerebral performance category (CPC) at 6 months. Poor outcome was defined as CPC 3-5. Sixty-two patients with OHCA of presumed cardiac cause were included. NSE had best prognostic accuracy for poor outcome at 48 hours with a receiver operating characteristic area under curve (AUC) of 0.94 (95% confidence interval [CI] 0.87-1). The combination of NSE with TnT, both at 48 hours, increased the AUC to 0.98 (95% CI 0.95-1, likelihood ratio [LR] test p-value 0.07, net reclassification index [NRI] <0.001); NSE and MR-proANP, both at 12 hours, yielded an AUC of 0.91 (95% CI 0.80-1, LR test p-value 0.0014, NRI p-value 0.003); NSE at 48 hours with MR-proANP at 12 hours yielded an AUC of 0.97 (95% CI 0.92-1, LR test p-value 0.055, NRI p-value 0.04). This pilot study suggests that a combination of biomarkers with NSE could be beneficial for improving early prognostication of long-term outcome following OHCA.
|
|
| 3. |
- Barchetta, Ilaria, et al.
(author)
-
Circulating pro-neurotensin levels predict bodyweight gain and metabolic alterations in children
- 2021
-
In: Nutrition, Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753. ; 31:3, s. 902-910
-
Journal article (peer-reviewed)abstract
- Background and aims: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life. Methods and results: For this longitudinal retrospective study, we studied 151 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24–28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired β-cell function to compensate for insulin-resistance (disposition index: r = −0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized β = 0.24; p = 0.036). Conclusions: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity.
|
|
| 4. |
- Belting, Mattias, et al.
(author)
-
Vasoactive Peptides with Angiogenesis-Regulating Activity Predict Cancer Risk in Males.
- 2012
-
In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 21:3, s. 513-522
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Tumor development requires angiogenesis, and antiangiogenesis has been introduced in the treatment of cancer patients; however, how the cardiovascular phenotype correlates with cancer risk remains ill-defined. Here, we hypothesized that vasoactive peptides previously implicated in angiogenesis regulation predict long-term cancer risk.METHODS: We measured midregional proatrial natriuretic peptide (MR-proANP), proadrenomedullin (MR-proADM), and C-terminal preprovasopressin (copeptin) in fasting plasma from participants of the Malmö Diet and Cancer Study that were free from cancer prior to the baseline exam in 1991 to 1994 (1,768 males and 2,293 females). We used Cox proportional hazards models to determine the time to first cancer event in relation to baseline levels of vasoactive peptides during a median follow-up of 15 years.RESULTS: First cancer events occurred in 366 males and in 368 females. In males, one SD increase of MR-proANP, copeptin, and MR-proADM was independently related to incident cancer [HR (95% CI)] by 0.85 (0.74-0.96), P = 0.012; 1.17 (1.04-1.32), P = 0.009; and 1.12 (0.99-1.26), P = 0.065, respectively, and a summed biomarker score identified an almost 2-fold difference in cancer risk between the top and bottom quartile (P < 0.001). In younger males, the biomarker score identified a more than 3-fold increase in risk between the top and bottom quartile (P < 0.001). Among females, we found no relationship between biomarkers and cancer incidence.CONCLUSIONS: Our data suggest that vasoactive peptide biomarkers predict cancer risk in males, particularly in younger males.Impact: Our findings may have implications for cancer risk prediction and present novel, potentially drug modifiable, mechanisms underlying cancer development. Cancer Epidemiol Biomarkers Prev; 1-10. ©2012 AACR.
|
|
| 5. |
- Bennet, Louise, et al.
(author)
-
The effect of a randomised controlled lifestyle intervention on weight loss and plasma proneurotensin
- 2022
-
In: BMC Endocrine Disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 22:1
-
Journal article (peer-reviewed)abstract
- AIMS: Proneurotensin (Pro-NT) is a strong predictor of cardiometabolic disease including type 2 diabetes and obesity, however, the effect of lifestyle change on Pro-NT has not been investigated in this context. Middle Eastern (ME) immigrants represent the largest and fastest growing minority population in Europe and are a high-risk population for obesity and type 2 diabetes. In this randomised controlled lifestyle intervention (RCT) addressing ME immigrants to Sweden where weight-loss was previously studied as the main outcome, as a secondary analysis we aimed to study change in Pro-NT during follow-up and if baseline Pro-NT predicted weight loss.METHODS: Immigrants from the Middle East at high risk for type 2 diabetes were invited to participate in this RCT adapted lifestyle intervention of four months' duration. The intervention group (N = 48) received a culturally adapted lifestyle intervention comprising seven group sessions and a cooking class addressing healthier diet and increased physical activity. The control group (N = 44) received treatment as usual with information to improve lifestyle habits on their own. Data assessed using mixed effects regression.OUTCOMES: Primary outcome; change in Pro-NT. Secondary outcome; change in BMI in relation to baseline plasma concentration of Pro-NT.RESULTS: During the four months follow up, weight was significantly reduced in the intervention (-2.5 kg) compared to the control group (0.8 kg) (β -0.12, 95% CI -0.24 to -0.01, P = 0.028). Pro-NT increased to a significantly greater extent in the intervention compared to the control group during follow up (28.2 vs. 3.5 pmol/L) (β 11.4; 4.8 to 18.02, P < 0.001). Change over time in BMI was associated with baseline Pro-NT (β 0.02; 0.01 to 0.04, P = 0.041).CONCLUSION: In consistence with data from surgical weight loss, this RCT paradoxically shows increased levels of Pro-NT during a multifactorial lifestyle intervention resulting in weight loss. Long term studies of Pro-NT following weight loss are needed.TRIAL REGISTRATION: This study is a secondary analysis of the RCT trial registered at www.CLINICALTRIALS.gov . REGISTRATION NUMBER: NCT01420198. Date of registration 19/08/2011. The performance and results of this trial conform to the CONSORT 2010 guidelines.
|
|
| 6. |
- Enhörning, Sofia, et al.
(author)
-
Genetic vasopressin 1b receptor variance in overweight and diabetes mellitus.
- 2016
-
In: European Journal of Endocrinology. - 1479-683X. ; 174:1, s. 69-75
-
Journal article (peer-reviewed)abstract
- Recently, imbalance in the vasopressin (AVP) system, measured as elevated levels of copeptin (the c-terminal part of the AVP pro-hormone) in plasma, was linked to development of abdominal obesity and diabetes mellitus (DM). Here, we aim to investigate if genetic variation of the human AVP receptor 1b gene (AVPR1B) is associated with measures of obesity and DM.
|
|
| 7. |
- Enhörning, Sofia, et al.
(author)
-
Plasma Copeptin, A Unifying Factor behind the Metabolic Syndrome.
- 2011
-
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96, s. 1065-1072
-
Journal article (peer-reviewed)abstract
- Context: Arginine vasopressin (AVP) is known to affect liver glycogenolysis, insulin, and glucagon secretion and pituitary ACTH release. We previously showed that high copeptin, the stable C-terminal fragment of AVP prohormone, is independently associated with hyperinsulinemia and future development of diabetes mellitus. Objective: The objective of the study was to examine whether plasma copeptin is associated with components of the metabolic syndrome (MetS) independently of insulin, diabetes mellitus, and environmental factors. Design, Setting, and Participants: This was a cross-sectional, population-based sample of 4742 subjects, aged 46-68 yr, 60% women, in Malmö, Sweden. Main Outcome Measure: Using multivariable logistic and linear regression, plasma copeptin was associated with components of the MetS. Results: Copeptin quartile (lowest quartile as reference) was, after adjustment for age, sex, insulin, and diabetes mellitus, associated with hypertension (odds ratios 1.04, 1.07, 1.31; P = 0.004), abdominal obesity (odds ratios 1.21, 1.16, 1.57; P = 0.002), obesity (odds ratios 1.25, 1.15, 1.49; P = 0.01), top quartile of c-reactive protein (odds ratios 1.11, 1.13, 1.32; P = 0.007), and MetS (adjusted for age and sex only) (odds ratios 1.53, 1.77, 1.86; P < 0.001). High copeptin levels were significantly associated with high fat intake, low physical activity, and borderline significantly associated with low socioeconomic status. The association between copeptin and components of the MetS was not affected after adjustment for these environmental factors. Conclusions: Our data suggest that increased activity of the AVP system is a unifying factor in the MetS and point to a new pharmacologically modifiable system of potential importance in the treatment of MetS and prevention of cardiovascular disease.
|
|
| 8. |
- Enhörning, Sofia, et al.
(author)
-
Plasma copeptin and the risk of diabetes mellitus.
- 2010
-
In: Circulation. - 1524-4539. ; 121:19, s. 51-2102
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Animal studies suggest that the arginine vasopressin system may play a role in glucose metabolism, but data from humans are limited. METHODS AND RESULTS: We analyzed plasma copeptin (copeptin), a stable C-terminal fragment of the arginine vasopressin prohormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742; mean age, 58 years; 60% women) and multivariable logistic regression, we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes mellitus at baseline, insulin resistance (top quartile of fasting plasma insulin among nondiabetic subjects), and incident diabetes mellitus on long-term follow-up. New-onset diabetes mellitus was ascertained through 3 national and regional registers. All models were adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein. In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes mellitus (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow-up, 174 subjects (4%) developed new-onset diabetes mellitus. The odds of developing diabetes mellitus increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios, 1.0, 1.37, 1.79, and 2.09; P for trend=0.004). The association with incident diabetes mellitus remained significant in analyses restricted to subjects with fasting whole blood glucose <5.4 mmol/L at baseline (adjusted odds ratios, 1.0, 1.80, 1.92, and 3.48; P=0.001). CONCLUSIONS: Elevated copeptin predicts increased risk for diabetes mellitus independently of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel antidiabetic treatments, and metabolic side effects from arginine vasopressin system modulation.
|
|
| 9. |
- Fawad, Ayesha, et al.
(author)
-
Magnitude of rise in proneurotensin is related to amount of triglyceride appearance in blood after standardized oral intake of both saturated and unsaturated fat
- 2020
-
In: Lipids in Health and Disease. - : Springer Science and Business Media LLC. - 1476-511X. ; 19:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: In rodents, neurotensin contributes to high fat diet induced obesity by facilitation of intestinal fat absorption. The effect of oral lipid load on plasma proneurotensin and relationship with plasma triglycerides in humans is unknown. AIM: To investigate the acute effects of an oral lipid load on proneurotensin and plasma triglycerides and their interrelationships in healthy individuals. SETTING/ METHODS: Twenty-two healthy subjects were given 150 mL of full milk cream (54 g fat) and 59 mL of pure olive oil (54 g fat) in the fasted state at two different occasions separated by at least 1 week in random order. Venous blood was drawn at fasted before 0 h (h) and at 1 h, 2 h and 4 h after ingestion. Post-ingested values of proneurotensin and plasma triglycerides were compared with fasting levels and post ingestion Area Under the Curve (AUC) of proneurotensin was correlated with that of plasma triglycerides. RESULTS: An immediate rise of plasma proneurotensin and plasma triglycerides were observed after ingestion of cream with maximum increase at 2 h for proneurotensin [mean (95% confidence interval)] of 22 (12-31) pmol/L (P < 0.001) and at 3 h for triglycerides of 0.60 (0.43-0.78) mmol/L (P < 0.001). Similarly, plasma proneurotensin and plasma triglycerides increased after ingestion of olive oil with maximum increase of proneurotensin at 3 h of 62 (46-78) pmol/L (P < 0.001) and plasma triglycerides at 3 h of 0.32 (0.18-0.45) mmol/L (P < 0.001). The post lipid load AUC for proneurotensin correlated significantly with the AUC for plasma triglycerides both after cream (r = 0.49, P = 0.021) and olive oil (r = 0.55, P = 0.008), respectively. CONCLUSION: Proneurotensin increases after an oral lipid load of both cream and olive oil and the rise of post-ingestion plasma triglycerides is significantly related to the rise of post-ingestion proneurotensin.
|
|
| 10. |
- Fawad, Ayesha, et al.
(author)
-
Proneurotensin Predicts Cardiovascular Disease in an Elderly Population
- 2018
-
In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:5, s. 1940-1947
-
Journal article (peer-reviewed)abstract
- Context: The gut hormone neurotensin promotes fat absorption, diet-induced weight gain, and liver steatosis. Its stable precursor-hormone fragment "proneurotensin" predicts cardiometabolic disease in middle-aged populations, especially in women. Objective: To test if proneurotensin predicts cardiovascular disease (CVD) and diabetes development in an elderly population and whether there are gender differences in this respect. Design, Setting, and Participants: Fasting proneurotensin was measured in plasma from 4804 participants (mean age 69±6 years) of the Malmö Preventive Project and subjects were followed up for development of CVD and diabetes during 5.4 years. Main Outcome Measures: Multivariate adjusted Cox proportional hazard models CVD were used to relate the proneurotensin to the risk of incident CVD and diabetes in all subjects and in genderstratified analyses. Results: In total, there were 456 first CVD events and 222 incident cases of diabetes. The hazard ratio [HR (95% confidence interval)] for CVD per 1 standard deviation (SD) increment of proneurotensin was 1.10 (1.01 to 1.21); P = 0.037, and the above vs below median HR was 1.27 (1.06 to 1.54); P = 0.011, with similar effect sizes in both genders. There was no significant association between proneurotensin and incident diabetes in the entire population (P = 0.52) or among men (P = 0.52). However, in women proneurotensin predicted diabetes incidence with a per 1 SD increment HR of 1.28 (1.30 to 1.59); P = 0.025 and an above vs below median HR of 1.41 (1.10 to 1.80); P = 0.007. Conclusions: In the elderly population, proneurotensin independently predicts development of CVD in both genders, whereas it only predicts diabetes in women.
|
|
| 11. |
- Fedorowski, Artur, et al.
(author)
-
Orthostatic blood pressure response, carotid intima-media thickness, and plasma fibrinogen in older nondiabetic adults.
- 2012
-
In: Journal of Hypertension. - 1473-5598. ; 30:3, s. 522-529
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:: Although recent studies have indicated that both orthostatic hypotension and orthostatic hypertension (OHTN) independently predict cardiovascular events, the underlying mechanisms are still debatable. METHODS:: A total of 700 nondiabetic adults (43% men, age 64 years) were examined by orthostatic blood pressure (BP) test, carotid artery ultrasonography, and biochemical tests including plasma fibrinogen and lipid profile. Multivariate-adjusted logistic regression was applied to assess association of intima-media thickness (IMT) and P-fibrinogen with orthostatic hypotension and OHTN. In addition, distribution of IMT and P-fibrinogen across quintiles of orthostatic systolic BP (SBP) response was analyzed. RESULTS:: Orthostatic hypotension and OHTN were found in 40 (5.7%) and 45 (6.4%) study participants, respectively. Both IMT [odds ratio (OR), 95% confidence interval (CI) per one-SD increment: 1.27, 1.01-1.60; P = 0.04] and P-fibrinogen (OR 1.44, 1.07-1.93; P = 0.02) were associated with orthostatic hypotension in a crude model. After adjustment relationship between orthostatic hypotension and IMT was slightly attenuated (OR 1.26, 0.96-1.65; P = 0.09) but was substantially unchanged in regard to P-fibrinogen (OR 1.45, 1.06-1.99; P = 0.02). In contrast, OHTN showed no association with either IMT or P-fibrinogen (adjusted OR 1.09, 0.78-1.52; P = 0.61, and 0.97, 0.70-1.34; P = 0.84, respectively). Distribution of IMT across quintiles of orthostatic SBP response was U-shaped, whereas that of fibrinogen was more linear but none of borderline quintiles (with pronounced hypertensive or hypotensive response) significantly differed from the middle quintiles in a fully adjusted model. CONCLUSION:: In older nondiabetic adults only orthostatic hypotension seems to independently correlate with increased carotid atherosclerosis and systemic inflammation.
|
|
| 12. |
- Hallengren, Erik, et al.
(author)
-
Fasting levels of growth hormone are associated with carotid intima media thickness but are not affected by fluvastatin treatment
- 2017
-
In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 17:1
-
Journal article (peer-reviewed)abstract
- Background: Growth hormone (GH) has been linked to cardiovascular disease but the exact mechanism of this association is still unclear. We here test if the fasting levels of GH are cross-sectionally associated with carotid intima media thickness (IMT) and whether treatment with fluvastatin affects the fasting level of GH. Methods: We examined the association between GH and IMT in 4425 individuals (aged 46-68 years) included in the baseline examination (1991-1994) of the Malmö Diet and Cancer cardiovascular cohort (MDC-CC). From that cohort we then studied 472 individuals (aged 50-70 years) who also participated (1994-1999) in the β-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS), a randomized, double blind, placebo-controlled, single-center clinical trial. Using multivariate linear regression models we related the change in GH-levels at 12 months compared with baseline to treatment with 40 mg fluvastatin once daily. Results: In MDC-CC fasting values of GH exhibited a positive cross-sectional relation to the IMT at the carotid bulb independent of traditional cardiovascular risk factors (p = 0.002). In a gender-stratified analysis the correlation were significant for males (p = 0.005), but not for females (p = 0.09). Treatment with fluvastatin was associated with a minor reduction in the fasting levels of hs-GH in males (p = 0.05) and a minor rise in the same levels among females (p = 0.05). Conclusions: We here demonstrate that higher fasting levels of GH are associated with thicker IMT in the carotid bulb in males. Treatment with fluvastatin for 12 months only had a minor, and probably not clinically relevant, effect on the fasting levels of hs-GH.
|
|
| 13. |
|
|
| 14. |
- Magnusson, Martin, et al.
(author)
-
Low Plasma Level of Atrial Natriuretic Peptide Predicts Development of Diabetes: The Prospective Malmo Diet and Cancer Study.
- 2012
-
In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 97:2, s. 638-645
-
Journal article (peer-reviewed)abstract
- Context:The cardiac natriuretic peptides are involved in blood pressure regulation, and large cross-sectional studies have shown lower plasma levels of N-terminal pro-natriuretic peptide levels [N-terminal atrial natriuretic peptide (N-ANP) and N-terminal brain natriuretic peptide (N-BNP)] in patients with insulin resistance, obesity, and diabetes.Objective:In this study, we prospectively tested whether plasma levels of mid-regional ANP (MR-ANP) and N-BNP predict new-onset diabetes and long-term glucose progression.Design, Setting, and Patients:MR-ANP and N-BNP were measured in 1828 nondiabetic individuals of the Malmö Diet and Cancer cohort (mean age 60 yr; 61% women) who subsequently underwent a follow-up exam including an oral glucose tolerance test after a median follow-up time of 16 yr. Logistic regression was used to adjust for covariates.Results:During follow-up, 301 subjects developed new-onset diabetes. After full multivariate adjustment, MR-ANP was significantly inversely associated with incident diabetes (OR = 0.85; 95% CI = 0.73-0.99; P = 0.034) but not N-BNP (OR = 0.92; 95% CI = 0.80-1.06; P = 0.262). In fully adjusted linear regression models, the progression of fasting glucose during follow-up was significantly inversely related to baseline levels of MR-ANP (P = 0.004) but not N-BNP (P = 0.129). Quartile analyses revealed that the overall association was mainly accounted for by excess risk of incident diabetes in subjects belonging to the lowest quartile of MR-ANP. After full adjustment, the odds ratio for incident diabetes in the bottom compared with the top quartile of MR-ANP was 1.65 (OR = 1.08-2.51, P = 0.019) and 1.43 (OR = 1.04-1.96, P = 0.027) compared with all other subjects.Conclusion:Low plasma levels of MR-ANP predict development of future diabetes and glucose progression over time, suggesting a causal role of ANP deficiency in diabetes development.
|
|
| 15. |
- Marino, Rossella, et al.
(author)
-
Diagnostic and short-term prognostic utility of plasma pro-enkephalin (pro-ENK) for acute kidney injury in patients admitted with sepsis in the emergency department
- 2015
-
In: Journal of Nephrology. - : Springer Science and Business Media LLC. - 1724-6059 .- 1121-8428. ; 28:6, s. 717-724
-
Journal article (peer-reviewed)abstract
- Background Acute kidney injury (AKI) aggravates the prognosis of patients with sepsis. Reliable biomarkers for early detection of AKI in this setting are lacking. Enkephalins influence kidney function, and may have a role in AKI from sepsis. We utilized a novel immunoassay for plasma proenkephalin (pro-ENK), a stable surrogate marker for endogenous enkephalins, in patients hospitalized with sepsis, in order to assess its clinical utility. Methods In an observational retrospective study we enrolled 101 consecutive patients admitted to the emergency department (ED) with suspected sepsis. Plasma levels of pro-ENK and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated at ED arrival for their association with presence and severity of AKI and 7-day mortality. Results pro-ENK was inversely correlated to creatinine clearance (r = -0.72) and increased with severity of AKI as determined by RIFLE (risk, injury, failure, loss of function, end-stage renal disease) stages (p < 0.0001; pro-ENK median [interquartile range, IQR]) pmol/l: no AKI: 71 [41-97]; risk: 72 [51-120]; injury: 200 [104-259]; failure: 230 [104-670]; loss of function: 947 [273-811]. The majority of septic patients without AKI or at risk had pro-ENK concentrations within the normal range. While NGAL was similarly associated with AKI severity, it was strongly elevated already in septic patients without AKI. pro-ENK added predictive information to NGAL for detecting kidney dysfunction (added chi(2) 10.0, p = 0.0016). Admission pro-ENK outperformed creatinine clearance in predicting 7-day mortality (pro-ENK: chi(2) 13.4, p < 0.001, area under curve, AUC 0.69; creatinine clearance: chi(2) 4, p = 0.045, AUC: 0.61), and serial measurement improved prediction. Conclusions Use of pro-ENK in septic patients can detect the presence and severity of AKI. Moreover, pro-ENK is highly predictive of short-term mortality and could enable early identification of patients at risk of death.
|
|
| 16. |
- Melander, Olle, et al.
(author)
-
Novel and conventional biomarkers for prediction of incident cardiovascular events in the community.
- 2009
-
In: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 302:1, s. 49-57
-
Journal article (peer-reviewed)abstract
- CONTEXT: Prior studies have demonstrated conflicting results regarding how much information novel biomarkers add to cardiovascular risk assessment. OBJECTIVE: To evaluate the utility of contemporary biomarkers for predicting cardiovascular risk when added to conventional risk factors. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 5067 participants (mean age, 58 years; 60% women) without cardiovascular disease from Malmö, Sweden, who attended a baseline examination between 1991 and 1994. Participants underwent measurement of C-reactive protein (CRP), cystatin C, lipoprotein-associated phospholipase 2, midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide, and N-terminal pro-B-type natriuretic peptide (N-BNP) and underwent follow-up until 2006 using the Swedish national hospital discharge and cause-of-death registers and the Stroke in Malmö register for first cardiovascular events (myocardial infarction, stroke, coronary death). MAIN OUTCOME MEASURES: Incident cardiovascular and coronary events. RESULTS: During median follow-up of 12.8 years, there were 418 cardiovascular and 230 coronary events. Models with conventional risk factors had C statistics of 0.758 (95% confidence interval [CI], 0.734 to 0.781) and 0.760 (0.730 to 0.789) for cardiovascular and coronary events, respectively. Biomarkers retained in backward-elimination models were CRP and N-BNP for cardiovascular events and MR-proADM and N-BNP for coronary events, which increased the C statistic by 0.007 (P = .04) and 0.009 (P = .08), respectively. The proportion of participants reclassified was modest (8% for cardiovascular risk, 5% for coronary risk). Net reclassification improvement was nonsignificant for cardiovascular events (0.0%; 95% CI, -4.3% to 4.3%) and coronary events (4.7%; 95% CI, -0.76% to 10.1%). Greater improvements were observed in analyses restricted to intermediate-risk individuals (cardiovascular events: 7.4%; 95% CI, 0.7% to 14.1%; P = .03; coronary events: 14.6%; 95% CI, 5.0% to 24.2%; P = .003). However, correct reclassification was almost entirely confined to down-classification of individuals without events rather than up-classification of those with events. CONCLUSIONS: Selected biomarkers may be used to predict future cardiovascular events, but the gains over conventional risk factors are minimal. Risk classification improved in intermediate-risk individuals, mainly through the identification of those unlikely to develop events.
|
|
| 17. |
- Melander, Olle, et al.
(author)
-
Stable Peptide of the Endogenous Opioid Enkephalin Precursor and Breast Cancer Risk.
- 2015
-
In: Journal of Clinical Oncology. - 1527-7755. ; 33:24, s. 81-2632
-
Journal article (peer-reviewed)abstract
- In experimental studies, enkephalins (ENKs) and related opioids have been implicated as negative regulators of breast cancer development by enhancing immune-mediated tumoral defense as well as directly inhibiting cancer cells. We hypothesized that plasma levels of ENKs are predictive of the long-term breast cancer risk. Therefore, our objective was to measure pro-ENK A, a surrogate for mature ENK, and evaluate its predictive value for the development of breast cancer in a large population of middle-aged women and an independent study population.
|
|
| 18. |
- Melander, Olle, et al.
(author)
-
Validation of plasma proneurotensin as a novel biomarker for the prediction of incident breast cancer.
- 2014
-
In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 23:8, s. 1672-1676
-
Journal article (peer-reviewed)abstract
- Background: High fasting plasma proneurotensin concentration was associated with the development of breast cancer in the Malmö Diet and Cancer Study (MDCS). Here we aimed at replicating the initial finding in an independent second cohort. Methods: The Malmö Preventive Project (MPP) is a population study and comprised 18 240 subjects when examined 2002-2006. Of women without history of breast cancer at examination, we included all who developed breast cancer during follow-up (n=130) until December 31st 2010 and a random sample of women without breast cancer until end of follow-up (n=1439) for baseline plasma proneurotensin assessment (mean age 70.0±4.4 years). Proneurotensin was measured in fasted plasma samples and was related to the risk of later breast cancer development using multivariate logistic regression. Results: Proneurotensin (odds ratio [OR] per SD increment of log-transformed proneurotensin) was significantly related to incident breast cancer (OR, 2.09; 95% CI, 1.79-2.44; P < 0.001; adjusted for age, BMI, smoking and hormone replacement therapy). The effect estimate in MPP was larger than in the discovery cohort (MDCS) with the main difference between the two cohorts being that women of the MPP study were on the average about 10 years older and follow-up time shorter compared to the MDCS. Conclusion: As initially found in the MDCS, fasting plasma proneurotensin was significantly associated with the development of breast cancer also in the MPP study. Impact: Measurement of plasma proneurotensin warrants further investigation as a blood based marker for early breast cancer detection.
|
|
| 19. |
- Molvin, John, et al.
(author)
-
Bioactive adrenomedullin, proenkephalin A and clinical outcomes in an acute heart failure setting
- 2019
-
In: Open Heart. - : BMJ. - 2053-3624. ; 6:2
-
Journal article (peer-reviewed)abstract
- Objectives In an acute heart failure (AHF) setting, proenkephalin A 119-159 (penKid) has emerged as a promising prognostic marker for predicting worsening renal function (WRF), while bioactive adrenomedullin (bio-ADM) has been proposed as a potential marker for congestion. We examined the diagnostic value of bio-ADM in congestion and penKid in WRF and investigated the prognostic value of bio-ADM and penKid regarding mortality, rehospitalisation and length of hospital stay in two separate European AHF cohorts. Methods Bio-ADM and penKid were measured in 530 subjects hospitalised for AHF in two cohorts: Swedish HeArt and bRain failure inVESTigation trial (HARVEST-Malmö) (n=322, 30.1% female; mean age 75.1+11.1 years; 12 months follow-up) and Italian GREAT Network Rome study (n=208, 54.8% female; mean age 78.5+9.9 years; no follow-up available). Results PenKid was associated with WRF (area under the curve (AUC) 0.65, p<0.001). In multivariable logistic regression analysis of the pooled cohort, penKid showed an independent association with WRF (adjusted OR (aOR) 1.74, p=0.004). Bio-ADM was associated with peripheral oedema (AUC 0.71, p<0.001), which proved to be independent after adjustment (aOR 2.30, p<0.001). PenKid was predictive of in-hospital mortality (OR 2.24, p<0.001). In HARVEST-Malmö, both penKid and bio-ADM were predictive of 1-year mortality (aOR 1.34, p=0.038 and aOR 1.39, p=0.030). Furthermore, bio-ADM was associated with rehospitalisation (aOR 1.25, p=0.007) and length of hospital stay (β=0.702, p=0.005). Conclusion In two different European AHF cohorts, bio-ADM and penKid perform as suitable biomarkers for early detection of congestion severity and WRF occurrence, respectively, and are associated with pertinent clinical outcomes.
|
|
| 20. |
- Newton-Cheh, Christopher, et al.
(author)
-
Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure
- 2009
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:3, s. 348-353
-
Journal article (peer-reviewed)abstract
- We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 10(-68)). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were also found to be associated with lower systolic (P = 2 x 10(-6) and 6 x 10(-5), respectively) and diastolic blood pressure (P = 1 x 10(-6) and 5 x 10(-5)), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 x 10(-5); OR = 0.90, 95% CI = 0.85-0.95, P = 2 x 10(-4), respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.
|
|
| 21. |
- Rosenqvist, Mari, et al.
(author)
-
Proenkephalin a 119-159 (penKid) - a novel biomarker for acute kidney injury in sepsis : an observational study
- 2019
-
In: BMC Emergency Medicine. - : Springer Science and Business Media LLC. - 1471-227X. ; 19
-
Journal article (peer-reviewed)abstract
- Background: Sepsis is a leading cause of death worldwide and a major challenge for physicians to predict and manage. Proenkephalin A 119-159 (penKid) is a reliable surrogate marker for the more unstable endogenous opioid peptide enkephalin, which has previously been shown to predict both acute and chronic kidney disease. The aim of this prospective observational study was to assess penKid as a predictor of acute kidney injury (AKI), multi-organ failure and mortality in sepsis among unselected sepsis patients presenting to the emergency department (ED). Method: We enrolled 644 patients consecutively during office-hours (6 AM-6 PM) between December 1, 2013 and February 1, 2015. Fifty-six patients were excluded due to incomplete data. We measured penKid in 588 adult patients (patients under 18 years of age were excluded) with sepsis (≥2SIRS criteria + suspected infection) upon admission to the ED at Skåne University Hospital, Malmö, Sweden. Logistic regression analysis was used to relate levels of penKid at presentation to AKI, multi-organ failure, 28-day mortality and progression of renal SOFA subscore. Odds ratios are presented as the number of standard deviations from the mean of log-transformed penKid. Results: In age and sex adjusted models, penKid predicted AKI within 48 h and 7 days, but these associations were attenuated after additional adjustment for estimated creatinine-based glomerular filtration rate (eGFR). In models adjusted for age, sex and eGFR, penKid significantly predicted progression from rSOFA = 0 and ≤ 1 to higher rSOFA scores as well as multi-organ failure and mortality. In contrast, eGFR did not predict 28-day mortality. Conclusion: PenKid is an effective predictor of renal injury, severe multi-organ failure and mortality in unselected sepsis patients presenting to the emergency department.
|
|
| 22. |
- Schiopu, Alexandru, et al.
(author)
-
Plasma procalcitonin and the risk of cardiovascular events and death: a prospective population-based study.
- 2012
-
In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 272:5, s. 484-491
-
Journal article (peer-reviewed)abstract
- Objectives: A number of inflammatory biomarkers such as C reactive protein (CRP) are independent predictors of cardiovascular risk. The inflammatory biomarker procalcitonin (PCT) has previously been shown to be associated with coronary atherosclerosis and the metabolic syndrome. We evaluated the ability of PCT to predict future cardiovascular events in a population of apparently healthy individuals. Design: We measured plasma PCT levels in 3713 subjects with no previous history of cardiovascular disease, randomly selected from the Malmö Diet and Cancer cohort. The correlation between PCT concentration and the incidence of coronary events, stroke and cardiovascular death over a median follow-up period of 13.7 years was studied using a Cox regression analysis corrected for age, sex, CRP level, traditional risk factors and renal function. Results: Age and sex were strong determinants of PCT; the concentration of PCT was significantly higher in men than in women. PCT was associated with several of the established cardiovascular risk factors (CRP, hypertension, diabetes and renal function,) as determined by multivariate linear regression. Of note, PCT was inversely correlated with HDL and smoking. We found significant correlations between PCT levels, coronary events and cardiovascular death. However, these relationships lost statistical significance when the analysis was corrected for CRP and the traditional risk factors. Conclusions: This is the largest population-based prospective study to demonstrate a positive association between plasma PCT levels and cardiovascular risk in subjects with no previous history of acute cardiovascular events. However, the high degree of covariation between PCT and other cardiovascular risk factors limits the value of PCT as an independent cardiovascular risk predictor. © 2012 The Association for the Publication of the Journal of Internal Medicine.
|
|
| 23. |
- Schomburg, Lutz, et al.
(author)
-
Seleno protein-P deficiency predicts cardiovascular disease and death
- 2019
-
In: Nutrients. - : MDPI AG. - 2072-6643. ; 11:8
-
Journal article (peer-reviewed)abstract
- Selenoprotein-P (SELENOP) is the main carrier of selenium to target organs and reduces tissue oxidative stress both directly and by delivering selenium to protective selenoproteins. We tested if the plasma concentration of SELENOP predicts cardiovascular morbidity and mortality in the primary preventive setting. SELENOP was measured from the baseline exam in 2002–2006 of the Malmö Preventive Project, a population-based prospective cohort study, using a validated ELISA. Quintiles of SELENOP concentration were related to the risk of all-cause mortality, cardiovascular mortality, and a first cardiovascular event in 4366 subjects during a median (interquartile range) follow-up time of 9.3 (8.3–11) years using Cox proportional Hazards Model adjusting for cardiovascular risk factors. Compared to subjects in the lowest quintile of SELENOP, the risk of all three endpoints was significantly lower in quintiles 2–5. The risk (multivariate adjusted hazard ratio, 95% CI) decreased gradually with the lowest risk in quintile 4 for all-cause mortality (0.57, 0.48–0.69) (p < 0.001), cardiovascular mortality (0.52, 0.37–0.72) (p < 0.001), and first cardiovascular event (0.56, 0.44–0.71) (p < 0.001). The lower risk of a first cardiovascular event in quintiles 2–5 as compared to quintile 1 was significant for both coronary artery disease and stroke. We conclude that the 20% with lowest SELENOP concentrations in a North European population without history of cardiovascular disease have markedly increased risk of cardiovascular morbidity and mortality, and preventive selenium supplementation studies stratified for these subjects are warranted.
|
|
| 24. |
- Schulz, Christina-Alexandra, et al.
(author)
-
High Level of Fasting Plasma Proenkephalin-A Predicts Deterioration of Kidney Function and Incidence of CKD
- 2017
-
In: Journal of the American Society of Nephrology: JASN. - 1046-6673. ; 28:1, s. 291-303
-
Journal article (peer-reviewed)abstract
- High levels of proenkephalin-A (pro-ENK) have been associated with decreased eGFR in an acute setting. Here, we examined whether pro-ENK levels predict CKD and decline of renal function in a prospective cohort of 2568 participants without CKD (eGFR>60 ml/min per 1.73 m2) at baseline. During a mean follow-up of 16.6 years, 31.7% of participants developed CKD. Participants with baseline pro-ENK levels in the highest tertile had significantly greater yearly mean decline of eGFR (Ptrend<0.001) and rise of cystatin C (Ptrend=0.01) and creatinine (Ptrend<0.001) levels. Furthermore, compared with participants in the lowest tertile, participants in the highest tertile of baseline pro-ENK concentration had increased CKD incidence (odds ratio, 1.51; 95% confidence interval, 1.18 to 1.94) when adjusted for multiple factors. Adding pro-ENK to a model of conventional risk factors in net reclassification improvement analysis resulted in reclassification of 14.14% of participants. Genome-wide association analysis in 4150 participants of the same cohort revealed the strongest association of pro-ENK levels with rs1012178 near the PENK gene, where the minor T-allele associated with a 0.057 pmol/L higher pro-ENK level per allele (P=4.67x10-21). Furthermore, the T-allele associated with a 19% increased risk of CKD per allele (P=0.03) and a significant decrease in the instrumental variable estimator for eGFR (P<0.01) in a Mendelian randomization analysis. In conclusion, circulating plasma pro-ENK level predicts incident CKD and may aid in identifying subjects in need of primary preventive regimens. Additionally, the Mendelian randomization analysis suggests a causal relationship between pro-ENK level and deterioration of kidney function over time.
|
|
| 25. |
- Smith, Gustav, et al.
(author)
-
Assessment of conventional cardiovascular risk factors and multiple biomarkers for the prediction of incident heart failure and atrial fibrillation.
- 2010
-
In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 56:21, s. 1713-1719
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: the purpose of this study was to assess the predictive accuracy of conventional cardiovascular risk factors for incident heart failure and atrial fibrillation, and the added benefit of multiple biomarkers reflecting diverse pathophysiological pathways. BACKGROUND: heart failure and atrial fibrillation are interrelated cardiac diseases associated with substantial morbidity and mortality and increasing incidence. Data on prediction and prevention of these diseases in healthy individuals are limited. METHODS: in 5,187 individuals from the community-based MDCS (Malmö Diet and Cancer Study), we studied the performance of conventional risk factors and 6 biomarkers including midregional pro-atrial natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-adrenomedullin, cystatin C, C-reactive protein (CRP), and copeptin. RESULTS: during a mean follow-up of 14 years, 112 individuals were diagnosed with heart failure and 284 individuals with atrial fibrillation. NT-proBNP (hazard ratio [HR]: 1.63 per SD, 95% confidence interval [CI]: 1.29 to 2.06, p < 0.001), CRP (HR: 1.57 per SD, 95% CI: 1.28 to 1.94, p < 0.001), and MR-proANP (HR: 1.26 per SD, 95% CI: 1.02 to 1.56, p = 0.03) predicted incident heart failure independently of conventional risk factors and other biomarkers. MR-proANP (HR: 1.62, 95% CI: 1.42 to 1.84, p < 0.001) and CRP (HR: 1.18, 95% CI: 1.03 to 1.34, p = 0.01) independently predicted atrial fibrillation. Addition of biomarkers to conventional risk factors improved c-statistics from 0.815 to 0.842 for heart failure and from 0.732 to 0.753 for atrial fibrillation and the integrated discrimination improvement for both diseases (p < 0.001). Net reclassification improvement (NRI) with biomarkers was observed in 22% of individuals for heart failure (NRI, p < 0.001) and in 7% for atrial fibrillation (NRI, p = 0.06), mainly due to up-classification of individuals who developed disease (heart failure: 29%, atrial fibrillation: 19%). Addition of CRP to natriuretic peptides did not improve discrimination or reclassification. CONCLUSIONS: conventional cardiovascular risk factors predict incident heart failure and atrial fibrillation with reasonable accuracy in middle-age individuals free from disease. Natriuretic peptides, but not other biomarkers, improve discrimination modestly for both diseases above and beyond conventional risk factors and substantially improve risk classification for heart failure.
|
|
