| 1. |
- Dahle, Nina, et al.
(författare)
-
Nondipping blood pressure pattern predicts cardiovascular events and mortality in patients with atherosclerotic peripheral vascular disease
- 2023
-
Ingår i: Vascular Medicine. - : Sage Publications. - 1358-863X .- 1477-0377. ; 28:4, s. 274-281
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with peripheral vascular disease (PVD) are often underdiagnosed and undertreated. Nocturnal nondipping blood pressure (BP) pattern, as diagnosed by ambulatory BP monitoring (ABPM), is associated with increased cardiovascular risk, but has not been studied in patients with PVD. We aimed to investigate if a nondipping BP pattern predicts cardiovascular events or all-cause death in outpatients with PVD.Methods: Consecutive outpatients with carotid or lower-extremity PVD were examined with 24-hour ABPM (n = 396). Nondipping was defined as a < 10% fall in systolic BP level during night-time. We used Cox regression models adjusting for potential confounders. We also evaluated the incremental prognostic value of dipping status in the COPART risk score. Our primary composite outcome was cardiovascular events or all-cause death.Results: In the cohort (mean age 70; 40% women), 137 events occurred during a 5.1-year median follow-up; incident rate of 7.35 events per 100 person-years. Nondipping was significantly associated with outcome (hazard ratio 1.55, 95% CI 1.07-2.26, p = 0.021) in a fully adjusted model. When adding nondipping to the risk markers in the COPART risk score, the model fit significantly improved (chi(2) 7.91, p < 0.005) and the C-statistic increased from 0.65 to 0.67.Conclusion: In a cohort of outpatients with PVD, nondipping was an independent risk factor for future cardiovascular events or mortality and seemed to be a strong predictor in patients with carotid artery disease but not in lower-extremity PVD. Additional studies are needed to evaluate the clinical utility of ABPM for improved prevention in these high-risk patients. (ClinicalTrials.gov Identifier: NCT01452165)
|
|
| 2. |
- Dahle, Nina, et al.
(författare)
-
Poorly controlled ambulatory blood pressure in outpatients with peripheral arterial disease
- 2021
-
Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 126:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with peripheral arterial disease (PAD) are generally less intensively managed than patients with coronary heart disease (CHD), despite that their risk of complications is believed to be equivalent. Identification of PAD patients at risk of poorly controlled blood pressure (BP) could lead to improved treatment, thus lowering the risk of cardiovascular (CV) complications. We aimed to describe the prevalence of poorly controlled cardiovascular (CV) risk factors, focusing on BP, in outpatients with PAD diagnosed in a vascular ultrasound laboratory.Methods: Consecutive outpatients with carotid and/or lower extremity PAD were included (n = 402) and examined with blood sampling, clinical BP, and 24-h ambulatory BP measurements. A poorly controlled clinical BP was defined as >= 140/90 mmHg, ambulatory BP >= 130/80 mmHg, low-density lipoprotein (LDL)-cholesterol level >= 2.5 mmol/L, and glycated hemoglobin (HbA1c) level >53 mmol/mol in those with diabetes.Results: Most of the patients had poorly controlled clinical (76.6%) and ambulatory BP (51.7%) profiles. Antihypertensive medications were prescribed in 84% of the patients. However, >40% of them used only 0-1 medication, and <25% of them used three or more agents. Clinical BP, a low number of medications, body mass index, and the presence of diabetes independently predicted a poorly controlled ambulatory BP. Nearly one-third of the patients were smokers, and most of the cohort had an LDL-cholesterol level of >= 2.5 mmol/L. An HbA1c level of >53 mmol/mol was present in 55% of diabetic patients.Conclusion: Poorly controlled clinical and ambulatory systolic BP profiles were common. In addition, suboptimal control of other important CV risk factors was detected. The findings of this study highlight the need for better preventive efforts against CV risk factors in outpatients with PAD.
|
|
| 3. |
- Jönelid, Birgitta, et al.
(författare)
-
Screening of biomarkers for prediction of multisite artery disease in patients with recent myocardial infarction
- 2021
-
Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 81:5, s. 353-360
-
Tidskriftsartikel (refereegranskat)abstract
- A few studies have examined biomarkers in patients with myocardial infarction (MI) and peripheral artery disease (PAD), i.e. multisite artery disease (MSAD). The aim of the study was firstly, to associate biomarkers with the occurrence of PAD/MSAD and secondly, if those can, in addition to clinical characteristics, identify MI patients with MSAD.In two prospectively observational studies including unselected patients with recent MI, PAD was defined as an abnormal ankle-brachial index (ABI) score (1.4). The proximity extension assay (PEA) technique was used, simultaneously analyzing 92 biomarkers with association to cardiovascular disease. Biomarkers were tested for univariate associations with PAD. Random forest was used to identify biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics was analyzed by the c-statistics. Nine biomarkers were identified as significantly associated with MSAD/PAD in the primary patient cohort, analyzed early after the MI. In the prediction analysis, six biomarkers were identified associated with PAD. Three of these; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) improved c-statistics when added to clinical characteristics from 0.683 (95% CI 0.610-0.756) to 0.715 (95% CI 0.645-0.784) in the primary patient cohort with a similar result, 0.729 (95% CI 0.687-0.770) to 0.752 (95% CI 0.771-0.792) in the secondary patient cohort. Biomarkers associated with inflammatory pathways are associated with MSAD in MI patients. Three biomarkers of 92; TNFR-1, TNFR-2 and GDF-15, in this exploratory added information in the prediction of MSAD and emphasis the importance of further studies.
|
|
| 4. |
- Lind, Lars, et al.
(författare)
-
Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes : Meta-Analyses and Mendelian Randomization Analyses
- 2021
-
Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 41:5, s. 1777-1788
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify causal pathophysiological mechanisms for atherosclerosis and incident cardiovascular events using protein measurements.APPROACH AND RESULTS: Carotid artery atherosclerosis was assessed by ultrasound, and 86 cardiovascular-related proteins were measured using the Olink CVD-I panel in 7 Swedish prospective studies (11 754 individuals). The proteins were analyzed in relation to intima-media thickness in the common carotid artery (IMT-CCA), plaque occurrence, and incident cardiovascular events (composite end point of myocardial infarction or ischemic stroke) using a discovery/replication approach in different studies. After adjustments for traditional cardiovascular risk factors, 11 proteins remained significantly associated with IMT-CCA in the replication stage, whereas 9 proteins were replicated for plaque occurrence and 17 proteins for incident cardiovascular events. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and MMP (matrix metalloproteinase)-12 were associated with both IMT-CCA and incident events, but the overlap was considerably larger between plaque occurrence and incident events, including MMP-12, TIM-1 (T-cell immunoglobulin and mucin domain 1), GDF (growth/differentiation factor)-15, IL (interleukin)-6, U-PAR (urokinase plasminogen activator surface receptor), LOX-1 (lectin-like oxidized LDL [low-density lipoprotein] receptor 1), and TRAIL-R2 (TNF [tumor necrosis factor]-related apoptosis-inducing ligand receptor 2). Only MMP-12 was associated with IMT-CCA, plaque, and incident events with a positive and concordant direction of effect. However, a 2-sample Mendelian randomization analysis suggested that increased MMP-12 may be protective against ischemic stroke (P=5.5x10(-7)), which is in the opposite direction of the observational analyses.CONCLUSIONS: The present meta-analysis discovered several proteins related to carotid atherosclerosis that partly differed in their association with IMT-CCA, plaque, and incident atherosclerotic disease. Mendelian randomization analysis for the top finding, MMP-12, suggests that the increased levels of MMP-12 could be a consequence of atherosclerotic burden rather than the opposite chain of events.
|
|
| 5. |
- Lönnberg, Lena, et al.
(författare)
-
Early screening for metabolic syndrome opens a window of opportunity : learnings from a long-term, population-based study
- 2023
-
Ingår i: European Heart Journal. - 0195-668X .- 1522-9645. ; 44:Supplement_2
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The metabolic syndrome (MetS) represents a cluster of risk factors that predict cardiovascular disease (CVD) and type 2 diabetes. Early detection of MetS opens up for a successful treatment of the cardiovascular (CV) risk factors involved, hopefully leading to later advent of CVD in the general population.Purpose: In this long-term, population-based study we aimed to investigate how presence of MetS, in middle-aged men and women, was associated with all-cause mortality and non-fatal CVD later in life.Methods: Between 1990 -1999 a screening program was conducted among 40- and 50-year-old inhabitants in the County of Västmanland, Sweden. Data on lifestyle habits and socio-economic status were collected. Total cholesterol, fasting blood glucose, blood pressure, weight, height, waist and hip circumference were measured. Individuals that met three or more of the following risk factors were classified with MetS: waist circumference: ≥102 cm (men) and ≥88 cm (women), total cholesterol: ≥6.1 mmol/ l, blood pressure: ≥130 and/ or ≥85 mm Hg (or previous diagnosis of hypertension) or fasting plasma glucose: ≥5.6 mmol/ l (or previous diagnosis of type 2 diabetes). A control group was identified with individuals from the same population, without MetS diagnosis. Each participant with MetS was matched to two controls regarding sex, age and date for the health examination. The association between midlife MetS and all-cause mortality and non-fatal CV events (stroke and myocardial infarction) was adjusted for age, sex, smoking, physical inactivity, educational level, BMI, hip circumference and living alone or with family members. Multivariable cox regression and Kaplan-Meier analyses were used.Results: A total number of 5084 individuals met the criteria for MetS and a control group of 10 168 individuals was identified. The median (Q1, Q3) follow-up time was 27 years (24.6, 30.1), corresponding to 130 820 and 269 696 person-years at risk in the MetS and the control group respectively. During follow up, 1317 MetS and 1904 control subjects died, implying 10 deaths in the MetS group and 7 deaths in the controls per 1000 person-years at risk (fig. 1). Cox analysis showed increased mortality in the MetS group compared to the controls, hazard ratio (HR) 1.30 (95% CI: 1.20-1.40); p<0.001. Non-fatal CV events in the MetS group and in the controls were 32.4% vs 22.8%, respectively (p<0.001); HR 1.35 (CI;1.25–1.46) (fig 2). Median time (Q1, Q3) for first non-fatal CV event was 16.8 years (9.9,22.3) in the MetS group and 19.1 (12.2, 23.6) for the controls.Conclusions: Results from this long-term, population-based study underline that the risk of non-fatal CVD and all-cause mortality was significantly higher in individuals with asymptomatic MetS. Present results support previous studies that early identification of MetS with screening programs might open a window of opportunity for prevention of CVD and premature death in the general population.
|
|
| 6. |
- Moberg, Lena, et al.
(författare)
-
Blood pressure screening in midlife aids in prediction of dementia later in life
- 2022
-
Ingår i: Upsala Journal of Medical Sciences. - : UPSALA MED SOC. - 0300-9734 .- 2000-1967. ; 127:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is substantial evidence that midlife hypertension is a risk factor for late life dementia. Our aim was to investigate if even high blood pressure at a single timepoint in midlife can predict an increased risk for all-cause dementia, Alzheimer's disease (AD), or vascular dementia (VaD) later in life. Methods: The community-based study population comprised 30,102 dementia-free individuals from the Westmannia Cardiovascular Risk Factors Study. The participants were aged 40 or 50 years when the health examination took place in 1990-2000. Diagnose registers from both hospitals and primary healthcare centers were used to identify individuals who after inclusion to the study developed dementia.The association between midlife high blood pressure (defined as systolic blood pressure >140 and/or diastolic blood pressure >90 mmHg) at a single timepoint and dementia was adjusted for age, gender, body mass index (BMI), fasting blood glucose, education, smoking, and physical activity level. Multivariate binary cox regression analyses were used. Results: After a mean follow-up time of 24 years resulting in 662,244 person/years, 761 (2.5%) individuals had been diagnosed with dementia. Midlife high blood pressure at a single timepoint predicted allcause dementia (hazard ratio [HR]: 1.22, 95% confidence interval [CI]: 1.02-1.45) and VaD (HR: 2.10, 95% CI: 1.47-3.00) but not AD (HR: 1.06, 95% CI: 0.81-1.38). Conclusion: This study suggests that even midlife high blood pressure at a single timepoint predicts allcause dementia and more than doubles the risk for VaD later in life independently of established confounders. Even though there was no such association with AD, this strengthens the importance of midlife health examinations in order to identify individuals with hypertension and initiate treatment.
|
|
| 7. |
- Nilsson, Göran, et al.
(författare)
-
Enigma of the cholesterol paradox in acute myocardial infarction : lessons from an 8-year follow-up of all-cause mortality in an age-matched and sex-matched case-control study with controls from the patients' recruitment area
- 2022
-
Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:7
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the impact of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) on long-term all-cause mortality (ACM) in patients with acute myocardial infarction (AMI) and controls.Design: Matched case-control study with 8-year follow-up.Setting: Vastmanland County Hospital, Vasteras, Sweden.Participants: Consecutive patients with AMI admitted to the coronary care unit from March 2005 to May 2010 and age-matched and sex-matched controls from the general population.Outcome measures: ACM.Results: Person-year at risk among patients with AMI and controls was 11 667 (cases: 5780 and controls: 5887). During follow-up, 199 patients and 84 controls died, implying 3.4 deaths among patients and 1.4 among controls per 100 person-years at risk. Unadjusted Cox analyses showed significantly increasing mortality by decreasing TC and LDL-C levels in both patients (HR=0.70, 95% CI 0.62 to 0.79, p<0.001, and HR=0.64, 95% CI 0.56 to 0.74, p<0.001) and controls (HR=0.73, 95% CI 0.60 to 0.89, p=0.002, and HR=0.74, 95% CI 0.59 to 0.93, p=0.010). After adjusting for clinical variables, the results for the patients remained significant. Cox analyses of the relations between mortality and TC and LDL-C below and above their respective medians revealed the following pattern. Patients: below medians were TC and LDL-C levels significantly inversely related to mortality; above medians there were no relations with mortality. Controls: below medians were TC and LDL-C levels significantly inversely related to mortality; above medians were LDL-C levels significantly positively related to mortality. Mean LDL-C level in patients with blood sampled >12 hours after symptom onset was 0.41 mmol/L lower than that in patients with blood sampled <= 12 hours (p=0.030). This LDL-C decrease was reasonably caused by ongoing AMI and reflects the difference in LDL-C levels between patients and controls.Conclusions: In patients with AMI, lower TC and LDL-C levels independently predict higher ACM. In their controls, LDL-C levels above the median independently predict higher ACM. This study adds to the body of evidence supporting the existence of a cholesterol paradox.
|
|
| 8. |
- Rudholm Feldreich, Tobias, et al.
(författare)
-
The association between plasma proteomics and incident cardiovascular disease identifies MMP-12 as a promising cardiovascular risk marker in patients with chronic kidney disease
- 2020
-
Ingår i: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 307, s. 11-15
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Previous proteomics efforts in patients with chronic kidney disease (CKD) have predominantly evaluated urinary protein levels. Therefore, our aim was to investigate the association between plasma levels of 80 cardiovascular disease-related proteins and the risk of major adverse cardiovascular events (MACE) in patients with CKD. Methods: Individuals with CKD stages 3-5 (eGFR below 60 ml min-1 [1.73 m]-2) from three community-based cohorts (PIVUS, ULSAM, SAVA), one diabetes cohort (CARDIPP) and one cohort with peripheral artery disease patients (PADVA) with information on 80 plasma protein biomarkers, assessed with a proximity extension assay, and follow-up data on incident MACE, were used as discovery sample. To validate findings and to asses generalizability to patients with CKD in clinical practice, an outpatient CKD-cohort (Malnutrition, Inflammation and Vascular Calcification (MIVC)) was used as replication sample. Results: In the discovery sample (total n = 1316), 249 individuals experienced MACE during 7.0 +/- 2.9 years (range 0.005-12.9) of follow-up, and in the replication sample, 71 MACE events in 283 individuals over a mean +/- SD change of 2.9 +/- 1.2 years (range 0.1-4.0) were documented. Applying Bonferroni correction, 18 proteins were significantly associated with risk of MACE in the discovery cohort, adjusting for age and sex in order of significance, GDF-15, FGF-23, REN, FABP4, IL6, TNF-R1, AGRP, MMP-12, AM, KIM-1, TRAILR2, TNFR2, CTSL1, CSF1, PlGF, CA-125, CCL20 and PAR-1 (p < 0.000625 for all). Only matrix metalloproteinase 12 (MMP-12) was significantly associated with an increased risk of MACE in the replication sample (hazard ratio (HR) per SD increase, 1.36, 95% CI (1.07-1.75), p = 0.013). Conclusions: Our proteomics analyses identified plasma MMP-12 as a promising cardiovascular risk marker in patients with CKD.
|
|
| 9. |
- Rydell, Andreas, et al.
(författare)
-
Plasma proteomics and lung function in four community-based cohorts
- 2021
-
Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 176
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Underlying mechanism leading to impaired lung function are incompletely understood.OBJECTIVES: To investigate whether protein profiling can provide novel insights into mechanisms leading to impaired lung function.METHODS: We used four community-based studies (n = 2552) to investigate associations between 79 cardiovascular/inflammatory proteins and forced expiratory volume in 1 s percent predicted (FEV1%) assessed by spirometry. We divided the cohorts into discovery and replication samples and used risk factor-adjusted linear regression corrected for multiple comparison (false discovery rate of 5%). We performed Mendelian randomization analyses using genetic and spirometry data from the UK Biobank (n = 421,986) to assess causality.MEASUREMENTS AND MAIN RESULTS: In cross-sectional analysis, 22 proteins were associated with lower FEV1% in both the discovery and replication sample, regardless of stratification by smoking status. The combined proteomic data cumulatively explained 5% of the variation in FEV1%. In longitudinal analyses (n = 681), higher plasma levels of growth differentiation factor 15 (GDF-15) and interleukin 6 (IL-6) predicted a more rapid 5-year decline in lung function (change in FEV1% per standard deviation of protein level -1.4, (95% CI, -2.5 to -0.3) for GDF-15, and -0.8, (95% CI, -1.5 to -0.2) for IL-6. Mendelian randomization analysis in UK-biobank provided support for a causal effect of increased GDF-15 levels and reduced FEV1%.CONCLUSIONS: Our combined approach identified GDF-15 as a potential causal factor in the development of impaired lung function in the general population. These findings encourage additional studies evaluating the role of GDF-15 as a causal factor for impaired lung function.
|
|
| 10. |
- Skau, Emma, et al.
(författare)
-
Are the results from a multiplex proteomic assay and a conventional immunoassay for NT-proBNP and GDF-15 comparable?
- 2023
-
Ingår i: Clinical Proteomics. - : BioMed Central (BMC). - 1542-6416 .- 1559-0275. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to compare absolute plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) obtained by a conventional immunoassay with the corresponding relative concentrations from a proximity extension assay (PEA) and compare the prognostic impact of the protein levels obtained from these assays.Methods: We evaluated 437 patients with peripheral arterial disease (PAD) and a population-based cohort of 643 individuals without PAD. Correlations were calculated using Spearman's rank correlation coefficients (rho). The discriminatory accuracy of the protein levels to predict future cardiovascular events was analyzed with Cox regression and presented as time-dependent areas under the receiver-operator-characteristic curves (tdAUCs).Results: For NT-proBNP, the two assays correlated with rho 0.93 and 0.93 in the respective cohort. The PEA values leveled off at higher values in both cohorts. The corresponding correlations for GDF-15 were 0.91 and 0.89. At 5 years follow-up, the tdAUCs in the patient cohort were similar for NT-proBNP and GDF-15 regardless of assay used (0.65-0.66). The corresponding tdAUCs in the population-based cohort were between 0.72 and 0.77.Conclusion: Except for the highest levels of NT-proBNP, we suggest that PEA data for NT-proBNP and GDF-15 reliably reflects absolute plasma levels and contains similar prognostic information.
|
|
