Publications by authors named "Peter Nilsson"

993 Publications

Plasma proneurotensin and prediction of cause-specific mortality in a middle-aged cohort during long-term follow-up.

J Clin Endocrinol Metab 2021 Oct 19. Epub 2021 Oct 19.

Lund University, Department of Clinical Sciences, Malmo, Sweden.

Purpose: To examine the prediction of Pro-NT on total and cause-specific mortality in a middle-aged cohort.

Methods: In the population-based middle-aged cohort (n=4632, mean age 57 years) of MDC study, Pro-NT was assessed and total as well as cause-specific mortality was studied. Main cause of death was based on the International Classification of Diseases (ICD).

Results: During a mean follow-up of 20±3 years, 950 men and 956 women died. There was significantly increased mortality risk in subjects belonging to the highest quartile (Q) of Pro-NT (Q4, Pro-NT ≥149 pmol/L) compared with Q 1-3 (Pro-NT <149 pmol/L), hazard ratio (HR), 95% confidence interval (CI) of 1.29 (1.17-1.42; P<0.001). Data was adjusted for sex and age. No significant interaction was observed between Pro-NT and gender on mortality risk. Individuals within Q4 vs. Q 1-3 had a HR of 1.41 (95% CI 1.18 -1.68; P<0.001) for death due to cardiovascular disease (n=595/4632); 2.53 (95% CI 1.37- 4.67; P=0.003), due to digestive tract disease (n= 42/4632), 1.62 (95% CI 1.04 - 2.52; P=0.032) due to mental and behavioral disease (n=90 /4632); and 1.91(95% CI 1.15 - 3.19; P=0.013) due to unspecific causes (n= 64/4632). There was no significant relationship between Pro-NT and deaths due to cancer, infections, neurological or other causes. Adjustment for cardiovascular risk factors only marginally changed these results.

Conclusions: The relationship between Pro-NT and total mortality risk was mainly driven by cardiovascular mortality, but high Pro-NT also predicts death from digestive, mental and behavioral disease and deaths attributed to unspecific causes.
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http://dx.doi.org/10.1210/clinem/dgab755DOI Listing
October 2021

Tau Protein Binding Modes in Alzheimer's Disease for Cationic Luminescent Ligands.

J Phys Chem B 2021 Oct 13. Epub 2021 Oct 13.

Department of Theoretical Chemistry and Biology, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, SE-106 91 Stockholm, Sweden.

The bi-thiophene-vinylene-benzothiazole (bTVBT4) ligand developed for Alzheimer's disease (AD)-specific detection of amyloid tau has been studied by a combination of several theoretical methods and experimental spectroscopies. With reference to the cryo-EM tau structure of the tau protofilament ( 2017, 547, 185), a periodic model system of the fibril was created, and the interactions between this fibril and bTVBT4 were studied with nonbiased molecular dynamics simulations. Several binding sites and binding modes were identified and analyzed, and the results for the most prevailing fibril site and ligand modes are presented. A key validation of the simulation work is provided by the favorable comparison of the theoretical and experimental absorption spectra of bTVBT4 in solution and bound to the protein. It is conclusively shown that the ligand-protein binding occurs at the hydrophobic pocket defined by the residues Ile360, Thr361, and His362. This binding site is not accessible in the Pick's disease (PiD) fold, and fluorescence imaging of bTVBT4-stained brain tissue samples from patients diagnosed with AD and PiD provides strong support for the proposed tau binding site.
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http://dx.doi.org/10.1021/acs.jpcb.1c06019DOI Listing
October 2021

Multidomain interventions: state-of-the-art and future directions for protocols to implement precision dementia risk reduction. A user manual for Brain Health Services-part 4 of 6.

Alzheimers Res Ther 2021 Oct 11;13(1):171. Epub 2021 Oct 11.

Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting several risk factors and disease mechanisms simultaneously, in individuals without dementia at baseline. Based on the findings, we formulate recommendations for implementing precision risk reduction strategies into new services called Brain Health Services. A literature search was conducted using medical databases (MEDLINE via PubMed and SCOPUS) to select relevant studies: non-pharmacological multidomain interventions (i.e., combining two or more intervention domains), target population including individuals without dementia, and primary outcomes including cognitive/functional performance changes and/or incident cognitive impairment or dementia. Further literature searches covered the following topics: sub-group analyses assessing potential modifiers for the intervention effect on cognition in the multidomain prevention trials, dementia risk scores used as surrogate outcomes in multidomain prevention trials, dementia risk scores in relation to brain pathology markers, and cardiovascular risk scores in relation to dementia. Multidomain intervention studies conducted so far appear to have mixed results and substantial variability in target populations, format and intensity of interventions, choice of control conditions, and outcome measures. Most trials were conducted in high-income countries. The differences in design between the larger, longer-term trials that met vs. did not meet their primary outcomes suggest that multidomain intervention effectiveness may be dependent on a precision prevention approach, i.e., successfully identifying the at-risk groups who are most likely to benefit. One such successful trial has already developed an operational model for implementing the intervention into practice. Evidence on the efficacy of risk reduction interventions is promising, but not yet conclusive. More long-term multidomain randomized controlled trials are needed to fill the current evidence gaps, especially concerning low- and middle-income countries and integration of dementia prevention with existing cerebrovascular prevention programs. A precision risk reduction approach may be most effective for dementia prevention. Such an approach could be implemented in Brain Health Services.
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http://dx.doi.org/10.1186/s13195-021-00875-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507202PMC
October 2021

Multiomics Profiling of Alzheimer's Disease Serum for the Identification of Autoantibody Biomarkers.

J Proteome Res 2021 Oct 10. Epub 2021 Oct 10.

Chronic Disease Programme (UFIEC), Instituto de Salud Carlos III, Majadahonda, Madrid 28220, Spain.

New biomarkers of Alzheimer's disease (AD) with a diagnostic value in preclinical and prodromal stages are urgently needed. AD-related serum autoantibodies are potential candidate biomarkers. Here, we aimed at identifying AD-related serum autoantibodies using protein microarrays and mass spectrometry-based methods. To this end, an untargeted complementary screening using high-density (42,100 antigens) and low-density (384 antigens) planar protein-epitope signature tag (PrEST) arrays and an immunoprecipitation protocol coupled to mass spectrometry analysis were used for serum autoantibody profiling. From the untargeted screening phase, 377 antigens corresponding to 338 proteins were selected for validation. Out of them, IVD, CYFIP1, and ADD2 seroreactivity was validated using 128 sera from AD patients and controls by PrEST-suspension bead arrays, and ELISA or luminescence Halotag-based bead immunoassay using full-length recombinant proteins. Importantly, IVD, CYFIP1, and ADD2 showed in combination a noticeable AD diagnostic ability. Moreover, IVD protein abundance in the prefrontal cortex was significantly two-fold higher in AD patients than in controls by western blot and immunohistochemistry, whereas CYFIP1 and ADD2 were significantly down-regulated in AD patients. The panel of AD-related autoantigens identified by a comprehensive multiomics approach may provide new insights of the disease and should help in the blood-based diagnosis of Alzheimer's disease. Mass spectrometry raw data are available in the ProteomeXchange database with the access number PXD028392.
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http://dx.doi.org/10.1021/acs.jproteome.1c00630DOI Listing
October 2021

A cell-free high throughput assay for assessment of SARS-CoV-2 neutralizing antibodies.

N Biotechnol 2021 Oct 7;66:46-52. Epub 2021 Oct 7.

Division of Protein Technology, Department of Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden. Electronic address:

Highly accurate serological tests are key to assessing the prevalence of SARS-CoV-2 antibodies and the level of immunity in the population. This is important to predict the current and future status of the pandemic. With the recent emergence of new and more infectious SARS-CoV-2 variants, assays allowing for high throughput analysis of antibodies able to neutralize SARS-CoV-2 become even more important. Here, we report the development and validation of a robust, high throughput method, which enables the assessment of antibodies inhibiting the binding between the SARS-CoV-2 spike protein and angiotensin converting enzyme 2 (ACE2). The assay uses recombinantly produced spike-f and ACE2 and is performed in a bead array format, which allows analysis of up to 384 samples in parallel per instrument over seven hours, demanding only one hour of manual handling. The method is compared to a microneutralization assay utilising live SARS-CoV-2 and is shown to deliver highly correlating data. Further, a comparison with a serological method that measures all antibodies recognizing the spike protein shows that this type of assessment provides important insights into the neutralizing efficiency of the antibodies, especially for individuals with low antibody levels. This method can be an important and valuable tool for large-scale assessment of antibody-based neutralization, including neutralization of new spike variants that might emerge.
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http://dx.doi.org/10.1016/j.nbt.2021.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495044PMC
October 2021

Early life factors in relation to albuminuria and estimated glomerular filtration rate based on cystatin C and creatinine in adults from a Swedish population-based cohort study.

J Nephrol 2021 Oct 8. Epub 2021 Oct 8.

Department of Clinical Sciences, Skane University Hospital, Lund University, Ruth Lundskogs gata 14, 205 02, Malmö, Sweden.

Background: Early life factors influence the number of nephrons a person starts life with and a consequence of that is believed to be premature kidney ageing. Thus, we aimed to identify early life factors associated with cystatin C and creatinine-based estimated glomerular filtration (eGFR) rate equations and urine -albumin-to-creatinine ratio after a follow-up of 46-67 years.

Methods: The study included 593 Swedish subjects without diabetes mellitus from the Malmo Diet Cancer Cohort. Perinatal data records including birth weight, gestational age, placenta weight and maternal related risk factors were analysed. eGFR was determined by Chronic Kidney Disease Epidemiology (CKD-EPI), the Lund-Malmö revised and Caucasian, Asian, Paediatric, and Adult (CAPA) equations. Postnatal growth phenotypes were defined as low (≤ 0) or high (> 0) birth weight z-score, or low (≤ median) or high (> median) body mass index at 20 years of age.

Results: In women, lower birth weight was associated with lower eGFR (CAPA; CKD-EPI cystatin C). Birth weight z-score predicted adult albuminuria specifically in men (OR 0.75, 95% CI [0.58; 0.96]). Women with high birth weight z-score and low BMI at 20 years had lower eGFR (CAPA; CKD-EPI cystatin C; p = 0.04). Men with high birth weight z-score and high BMI at 20 years had lower risk for albuminuria (OR 0.35, 95% CI [0.12; 0.93]).

Conclusions: Lower birth weight, prematurity and postnatal growth curve have a potential sex- specific effect of early exposure to an adverse environment on lower cystatin C-based eGFR and albuminuria later in life. Cystatin C compared to creatinine -eGFR equations shows a higher ability to detect these findings.
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http://dx.doi.org/10.1007/s40620-021-01159-yDOI Listing
October 2021

The risk of chronic kidney disease in relation to anthropometric measures of obesity: A Swedish cohort study.

BMC Nephrol 2021 Oct 5;22(1):330. Epub 2021 Oct 5.

Department of Clinical Sciences in Malmö, Lund University, Internal Medicine - Epidemiology Research Group, Jan Waldenströms gata 15, 5th floor, Malmo, Sweden.

Background: It has been shown that individuals with obesity have a higher risk for chronic kidney disease (CKD). However, it is unclear which measure of obesity is most useful for prediction of CKD in the general population. The aim of this large prospective study was to explore the association between several anthropometric measures of obesity, i. e., body mass index (BMI), waist circumference (WC), waist circumference to height ratio (WHtR), waist-to-hip ratio (WHR), percentage of body fat (BF%), weight, height and incidence of hospitalizations due to CKD, in a population-based cohort study.

Methods: The 'Malmö Diet and Cancer Study (MDCS)' cohort in Sweden was examined during 1991 to 1996. A total of 28,449 subjects underwent measurement of anthropometric measures and blood pressure and filled out a questionnaire. Incidence of in- and outpatient hospital visits for CKD was monitored from the baseline examination over a mean follow-up of 18 years. Cox proportional hazards regression was used to explore the association between anthropometric measures and incidence of CKD, with adjustments for risk factors.

Results: The final study population included 26,723 subjects, 45-73 years old at baseline. Higher values of BMI, WC, WHR, WHtR and weight were associated with an increased risk of developing CKD in both men and women. Only in women, higher values of BF% was associated with higher risk of CKD. Comparing the 4 vs 1 quartile of the obesity measure, the highest hazard ratio (HR) for CKD in men was observed for BMI, HR 1.51 (95% CI: 1.18-1.94) and weight (HR 1.52 (95% CI: 1.19-1.94). For women the highest HR for CKD was observed for BF%, HR 2.01 (95% CI: 1.45-2.78).

Conclusions: In this large prospective study, all anthropometric measures of obesity were associated with a substantially increased incidence of CKD, except for BF% in men. Some measures were slightly more predictive for the risk of CKD than others such as BMI and weight in men and BF% in women. In clinical daily practice use of all anthropometric measures of obesity might be equally useful to assess the risk of developing CKD. This study supports the strong evidence for an association between obesity and CKD.
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http://dx.doi.org/10.1186/s12882-021-02531-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491415PMC
October 2021

Distinct conformers of amyloid beta accumulate in the neocortex of patients with rapidly progressive Alzheimer's disease.

J Biol Chem 2021 Sep 30;297(5):101267. Epub 2021 Sep 30.

Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA; Department of Neurology, Case Western Reserve University, Cleveland, Ohio, USA. Electronic address:

Amyloid beta (Aβ) deposition in the neocortex is a major hallmark of Alzheimer's disease (AD), but the extent of deposition does not readily explain phenotypic diversity and rate of disease progression. The prion strain-like model of disease heterogeneity suggests the existence of different conformers of Aβ. We explored this paradigm using conformation-dependent immunoassay (CDI) for Aβ and conformation-sensitive luminescent conjugated oligothiophenes (LCOs) in AD cases with variable progression rates. Mapping the Aβ conformations in the frontal, occipital, and temporal regions in 20 AD patients with CDI revealed extensive interindividual and anatomical diversity in the structural organization of Aβ with the most significant differences in the temporal cortex of rapidly progressive AD. The fluorescence emission spectra collected in situ from Aβ plaques in the same regions demonstrated considerable diversity of spectral characteristics of two LCOs-quatroformylthiophene acetic acid and heptaformylthiophene acetic acid. Heptaformylthiophene acetic acid detected a wider range of Aβ deposits, and both LCOs revealed distinct spectral attributes of diffuse and cored plaques in the temporal cortex of rapidly and slowly progressive AD and less frequent and discernible differences in the frontal and occipital cortex. These and CDI findings indicate a major conformational diversity of Aβ accumulating in the neocortex, with the most notable differences in temporal cortex of cases with shorter disease duration, and implicate distinct Aβ conformers (strains) in the rapid progression of AD.
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http://dx.doi.org/10.1016/j.jbc.2021.101267DOI Listing
September 2021

An evaluation of a FluoroSpot assay as a diagnostic tool to determine SARS-CoV-2 specific T cell responses.

PLoS One 2021 30;16(9):e0258041. Epub 2021 Sep 30.

Department of Clinical Sciences, Karolinska Institute, Danderyd Hospital, Stockholm, Sweden.

Numerous assays evaluating serological and cellular responses have been developed to characterize immune responses against SARS-CoV-2. Serological assays are both cost- and time-effective compared to cellular assays, but cellular immune responses may provide a diagnostic value to determine previous SARS-CoV-2 infection in seronegative individuals. However, potential cross-reactive T cell responses stemming from prior encounters with human coronaviruses (HCoVs) may affect assay specificity. In this study, we evaluated the specificity and sensitivity of a SARS-CoV-2 IFN-γ Release Assay (IGRA) based on the FluoroSpot method employing commercially available SARS-CoV-2-specific peptide pools, as well as an in-house designed SARS-CoV-2 peptide pool restricted to 5 amino acid stretches or less aligning with endemic HCoVs. Blood samples were obtained from healthcare workers (HCW) 5-6 months post SARS-CoV-2 spike (S) IgG and nucleocapsid (N) IgG dual seroconversion (n = 187) and HCW who had been S IgG and N IgG dual seronegative at repeated occasions, including the current sampling time point (n = 102). In addition, samples were obtained 4 to 5 months post infection from 55 polymerase chain reaction (PCR)-confirmed COVID-19 patients. Assay specificity and sensitivity were calculated with serology as a reference standard for HCW. The in-house generated peptide pool displayed a specificity of 96.1%, while the commercially available peptide pools displayed specificities of 80.4% and 85.3%, respectively. Sensitivity was higher in a cohort of previously hospitalized COVID-19 patients (96.4% and 84.0% for the commercially available peptide pools and 92.7% for the in-house generated peptide pool) compared to the HCW cohort (92.0% and 66.8% for the commercially available peptide pools and 76.0% for the in-house generated peptide pool). Based on these findings, the individual diagnostic value of T cell immune responses against SARS-CoV-2 currently appears to be limited but remain an important research tool ahead.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258041PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483319PMC
October 2021

Pro-Enkephalin and its association with renal function in Middle Eastern immigrants and native Swedes.

Scand J Clin Lab Invest 2021 Sep 28:1-6. Epub 2021 Sep 28.

Department of Clinical Sciences, Lund University, Malmö, Sweden.

Iraqi-born immigrants residing in Sweden exhibit lower blood pressure as well as better renal function despite an overall worse metabolic risk profile in comparison with native Swedes. This may indicate the presence of cardiorenal protective mechanisms in the Middle Eastern population. Hence, the aim of this study was to investigate whether the association between renal function and Pro-Enkephalin (PENK), a biomarker predictive of both acute and chronic kidney dysfunction, differs across ethnicities. The MEDIM population-based study including a cohort of women and men, born in Iraq or Sweden, aged 30-75 years was conducted in Malmö, Sweden, from 2010 to 2012. The study included fasting blood samples, physical examinations and self-administrated questionnaires. Despite significantly better renal function assessed by creatinine-based eGFR in the Iraqi group, levels of PENK did not differ between the groups, (70.0 pmol/L, born in Iraq ( = 1263) vs 71.1, born in Sweden ( = 689),  .4). However, the association between PENK and renal function was relatively weaker in the Iraqi born group, as supported by a significant interaction between PENK and country of birth (= Country of birth x PENK = ). This observational study suggests that the association between renal function and PENK was weaker in Middle Eastern immigrants. This is of interest as PENK may exhibit a direct effect on renal function, however further research is needed including studies on causality.
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http://dx.doi.org/10.1080/00365513.2021.1979243DOI Listing
September 2021

Carotid-Femoral Pulse Transit Time Variability Predicted Mortality and Improved Risk Stratification in the Elderly.

Hypertension 2021 Nov 27;78(5):1287-1295. Epub 2021 Sep 27.

Department of Clinical Science, Lund University, Sweden (I.F.M., Y.B., M.P., G.E., P.M.N.).

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17891DOI Listing
November 2021

Covid-19 in patients with chronic lymphocytic leukemia: clinical outcome and B- and T-cell immunity during 13 months in consecutive patients.

Leukemia 2021 Sep 25. Epub 2021 Sep 25.

Department of Hematology, Karolinska University Hospital Solna, Stockholm, Sweden.

We studied clinical and immunological outcome of Covid-19 in consecutive CLL patients from a well-defined area during month 1-13 of the pandemic. Sixty patients (median age 71 y, range 43-97) were identified. Median CIRS was eight (4-20). Patients had indolent CLL (n = 38), had completed (n = 12) or ongoing therapy (n = 10). Forty-six patients (77%) were hospitalized due to severe Covid-19 and 11 were admitted to ICU. Severe Covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except CIRS (p < 0.05). Fourteen patients (23%) died; age ≥75 y was the only significant risk factor (p < 0.05, multivariate analysis with limited power). Comparing month 1-6 vs 7-13 of the pandemic, deaths were numerically reduced from 32% to 18%, ICU admission from 37% to 15% whereas hospitalizations remained frequent (86% vs 71%). Seroconversion occurred in 33/40 patients (82%) and anti-SARS-CoV-2 antibodies were detectable at six and 12 months in 17/22 and 8/11 patients, respectively. Most (13/17) had neutralizing antibodies and 19/28 had antibodies in saliva. SARS-CoV-2-specific T-cells (ELISpot) were detected in 14/17 patients. Covid-19 continued to result in high admission even among consecutive and young early- stage CLL patients. A robust and durable B and/or T cell immunity was observed in most convalescents.
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http://dx.doi.org/10.1038/s41375-021-01424-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475381PMC
September 2021

Good night and sleep well! - But what is really a healthy sleep?

J Intern Med 2021 Sep 21. Epub 2021 Sep 21.

Department of Clinical Sciences, Skane University Hospital, Lund University, Malmö, Sweden.

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http://dx.doi.org/10.1111/joim.13373DOI Listing
September 2021

Machine Learning-Derived Echocardiographic Phenotypes Predict Heart Failure Incidence in Asymptomatic Individuals.

JACC Cardiovasc Imaging 2021 Sep 8. Epub 2021 Sep 8.

Centre d'Investigations Cliniques Plurithématique 1433, Université de Lorraine, Institut national de la santé et de la recherche médicale 1116, Centre Hospitalier Universitaire Régional de Nancy, France; French Clinical Research Infrastructure Network "Investigation" Network Initiative - Cardiovascular and Renal Clinical Trialists" Cardiovascular and Renal Clinical Trialists Network, France. Electronic address:

Objectives: This study sought to identify homogenous echocardiographic phenotypes in community-based cohorts and assess their association with outcomes.

Background: Asymptomatic cardiac dysfunction leads to a high risk of long-term cardiovascular morbidity and mortality; however, better echocardiographic classification of asymptomatic individuals remains a challenge.

Methods: Echocardiographic phenotypes were identified using K-means clustering in the first generation of the STANISLAS (Yearly non-invasive follow-up of Health status of Lorraine insured inhabitants) cohort (N = 827; mean age: 60 ± 5 years; men: 48%), and their associations with vascular function and circulating biomarkers were also assessed. These phenotypes were externally validated in the Malmö Preventive Project cohort (N = 1,394; mean age: 67 ± 6 years; men: 70%), and their associations with the composite of cardiovascular mortality (CVM) or heart failure hospitalization (HFH) were assessed as well.

Results: Three echocardiographic phenotypes were identified as "mostly normal (MN)" (n = 334), "diastolic changes (D)" (n = 323), and "diastolic changes with structural remodeling (D/S)" (n = 170). The D and D/S phenotypes had similar ages, body mass indices, cardiovascular risk factors, vascular impairments, and diastolic function changes. The D phenotype consisted mainly of women and featured increased levels of inflammatory biomarkers, whereas the D/S phenotype, consisted predominantly of men, displayed the highest values of left ventricular mass, volume, and remodeling biomarkers. The phenotypes were predicted based on a simple algorithm including e', left ventricular mass and volume (e'VM algorithm). In the Malmö cohort, subgroups derived from e'VM algorithm were significantly associated with a higher risk of CVM and HFH (adjusted HR in the D phenotype = 1.87; 95% CI: 1.04 to 3.37; adjusted HR in the D/S phenotype = 3.02; 95% CI: 1.71 to 5.34).

Conclusions: Among asymptomatic, middle-aged individuals, echocardiographic data-driven classification based on the simple e'VM algorithm identified profiles with different long-term HF risk. (4th Visit at 17 Years of Cohort STANISLAS-Stanislas Ancillary Study ESCIF [STANISLASV4]; NCT01391442).
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http://dx.doi.org/10.1016/j.jcmg.2021.07.004DOI Listing
September 2021

Impact of genetic risk score on the association between male childlessness and cardiovascular disease and mortality.

Sci Rep 2021 09 17;11(1):18526. Epub 2021 Sep 17.

Reproductive Medicine Centre, Skåne University Hospital, Malmö, Sweden.

Childless men are reported to have a higher risk of cardiovascular disease (CVD) and mortality. Information on inherited genetic risk for CVD has improved the predictive models. Presuming that childlessness is a proxy of infertility we aimed to investigate if childless men inherit more often genetic traits for CVD and if combining genetic and parenthood information improves predictive models for CVD morbidity and mortality. Data was sourced from a large prospective population-based cohort where genetic risk score (GRS) was calculated using two sets of either 27 (GRS 27) or 50 (GRS 50) single nucleotide polymorphisms (SNPs) previously found to be associated with CVD. Part of the participants (n = 2572 men) were randomly assigned to a sub-cohort with focus on CVD which served as an exploratory cohort. The obtained statistically significant results were tested in the remaining (confirmatory) part of the cohort (n = 9548 men). GRS distribution did not differ between childless men and fathers (p-values for interaction between 0.29 and 0.76). However, when using fathers with low GRS as reference high GRS was a strong predictor for CVD mortality, the HR (95% CI) increasing from 1.92 (1.10-3.36) for GRS 50 and 1.54 (0.87-2.75) for GRS 27 in fathers to 3.12 (1.39-7.04) for GRS50 and 3.73 (1.75-7.99) for GRS27 in childless men. The confirmatory analysis showed similar trend. Algorithms including paternal information and GRS were more predictive for CVD mortality at 5 and 10 years follow-ups when compared to algorithms including GRS only (AUC 0.88 (95% CI 0.84-0.92) and 0.86 (95% CI 0.84-0.90), and, AUC 0.81 (95% CI 0.75-0.87) and 0.78 (95% CI 0.73-0.82), respectively). Combining information on parental status and GRS for CVD may improve the predictive power of risk algorithms in middle-aged men. Childless men and those with severe infertility problem may be an important target group for prevention of CVD.
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http://dx.doi.org/10.1038/s41598-021-97733-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448891PMC
September 2021

Autoantibody profiles associated with clinical features in psychotic disorders.

Transl Psychiatry 2021 09 13;11(1):474. Epub 2021 Sep 13.

Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.

Autoimmune processes are suspected to play a role in the pathophysiology of psychotic disorders. Better understanding of the associations between auto-immunoglobulin G (IgG) repertoires and clinical features of mental illness could yield novel models of the pathophysiology of psychosis, and markers for biological patient stratification. We undertook cross-sectional detection and quantification of auto-IgGs in peripheral blood plasma of 461 people (39% females) with established psychotic disorder diagnoses. Broad screening of 24 individuals was carried out on group level in eight clinically defined groups using planar protein microarrays containing 42,100 human antigens representing 18,914 proteins. Autoantibodies indicated by broad screening and in the previous literature were measured using a 380-plex bead-based array for autoantibody profiling of all 461 individuals. Associations between autoantibody profiles and dichotomized clinical characteristics were assessed using a stepwise selection procedure. Broad screening and follow-up targeted analyses revealed highly individual autoantibody profiles. Females, and people with family histories of obesity or of psychiatric disorders other than schizophrenia had the highest overall autoantibody counts. People who had experienced subjective thought disorder and/or were treated with clozapine (trend) had the lowest overall counts. Furthermore, six autoantibodies were associated with specific psychopathology symptoms: anti-AP3B2 (persecutory delusions), anti-TDO2 (hallucinations), anti-CRYGN (initial insomnia); anti-APMAP (poor appetite), anti-OLFM1 (above-median cognitive function), and anti-WHAMMP3 (anhedonia and dysphoria). Future studies should clarify whether there are causal biological relationships, and whether autoantibodies could be used as clinical markers to inform diagnostic patient stratification and choice of treatment.
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http://dx.doi.org/10.1038/s41398-021-01596-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438048PMC
September 2021

Heart Failure Events in a Clinical Trial on Arterial Hypertension: New Insights Into the SPRINT Trial.

Hypertension 2021 Nov 13;78(5):1241-1247. Epub 2021 Sep 13.

Department of Clinical Sciences, Division of Cardiovascular Medicine, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden (T.K.).

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17360DOI Listing
November 2021

The impact of age and 24-h blood pressure on arterial health in acute ischemic stroke patients: The Norwegian stroke in the young study.

J Clin Hypertens (Greenwich) 2021 Sep 7. Epub 2021 Sep 7.

Department of Clinical Sciences, Lund University, Skane University Hospital, Malmö, Sweden.

The impact of age and 24-h ambulatory blood pressure (ABPM) on arterial stiffness and carotid intima-media thickness (cIMT) in ischemic stroke patients younger than 60 years of age is poorly explored. A total of 385 acute ischemic stroke patients (aged 49.6±9.7 years, 68% men) were prospectively included and grouped in younger (15-44 years, n = 93) and middle-aged (45-60 years, n = 292). Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV), and cIMT by carotid ultrasound. 24-h ABPM was recorded. The middle-aged stroke patients had higher prevalence of smoking, hypertension, diabetes mellitus, metabolic syndrome and hypercholesterolemia, and had higher PWV and cIMT (all p < .05). In multivariable linear regression analyses adjusted for sex, BMI, smoking, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, triglycerides, eGFR, systolic BP and concomitant antihypertensive treatment, 1SD (4.4 years) higher age was associated with higher PWV (β = 0.44,R = 0.46, p < .001) in the younger group, and with higher mean cIMT (β = 0.16, R = 0.21, p = .01) in the middle-aged group. In the middle-aged group, 24-h pulse pressure had a significant association with PWV (β = 0.18, R = 0.19, p = .009), while the association with cIMT was attenuated (β = 0.13, R = 0.16, p = .065). 24-h diastolic BP was associated with higher cIMT in the middle-aged group (β = 0.24, p < .001, R = 0.23), but not with PWV in either age groups. Among ischemic stroke patients < 60 years, higher age was associated with increased arterial stiffness for patients up to age 44 years, and with cIMT in middle-aged patients. 24-h pulse pressure was associated with arterial stiffness, and 24-h diastolic BP was associated with cIMT only in middle-aged patients.
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http://dx.doi.org/10.1111/jch.14361DOI Listing
September 2021

Development of humoral and cellular immunological memory against SARS-CoV-2 despite B cell depleting treatment in multiple sclerosis.

iScience 2021 Sep 2;24(9):103078. Epub 2021 Sep 2.

Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:04, 171 76 Stockholm, Sweden.

B cell depleting therapies (BCDTs) are widely used as immunomodulating agents for autoimmune diseases such as multiple sclerosis. Their possible impact on development of immunity to severe acute respiratory syndrome virus-2 (SARS-CoV-2) has raised concerns with the coronavirus disease 2019 (COVID-19) pandemic. We here evaluated the frequency of COVID-19-like symptoms and determined immunological responses in participants of an observational trial comprising several multiple sclerosis disease modulatory drugs (COMBAT-MS; NCT03193866) and in eleven patients after vaccination, with a focus on BCDT. Almost all seropositive and 17.9% of seronegative patients on BCDT, enriched for a history of COVID-19-like symptoms, developed anti-SARS-CoV-2 T cell memory, and T cells displayed functional similarity to controls producing IFN-γ and TNF. Following vaccination, vaccine-specific humoral memory was impaired, while all patients developed a specific T cell response. These results indicate that BCDTs do not abrogate SARS-CoV-2 cellular memory and provide a possible explanation as to why the majority of patients on BCDTs recover from COVID-19.
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http://dx.doi.org/10.1016/j.isci.2021.103078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410640PMC
September 2021

Robust humoral and cellular immune responses and low risk for reinfection at least 8 months following asymptomatic to mild COVID-19.

J Intern Med 2021 Aug 30. Epub 2021 Aug 30.

Department of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden.

Background: Emerging data support detectable immune responses for months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, but it is not yet established to what degree and for how long protection against reinfection lasts.

Methods: We investigated SARS-CoV-2-specific humoral and cellular immune responses more than 8 months post-asymptomatic, mild and severe infection in a cohort of 1884 healthcare workers (HCW) and 51 hospitalized COVID-19 patients. Possible protection against SARS-CoV-2 reinfection was analyzed by a weekly 3-month polymerase chain reaction (PCR) screening of 252 HCW that had seroconverted 7 months prior to start of screening and 48 HCW that had remained seronegative at multiple time points.

Results: All COVID-19 patients and 96% (355/370) of HCW who were anti-spike IgG positive at inclusion remained anti-spike IgG positive at the 8-month follow-up. Circulating SARS-CoV-2-specific memory T cell responses were detected in 88% (45/51) of COVID-19 patients and in 63% (233/370) of seropositive HCW. The cumulative incidence of PCR-confirmed SARS-CoV-2 infection was 1% (3/252) among anti-spike IgG positive HCW (0.13 cases per 100 weeks at risk) compared to 23% (11/48) among anti-spike IgG negative HCW (2.78 cases per 100 weeks at risk), resulting in a protective effect of 95.2% (95% CI 81.9%-99.1%).

Conclusions: The vast majority of anti-spike IgG positive individuals remain anti-spike IgG positive for at least 8 months regardless of initial COVID-19 disease severity. The presence of anti-spike IgG antibodies is associated with a substantially reduced risk of reinfection up to 9 months following asymptomatic to mild COVID-19.
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http://dx.doi.org/10.1111/joim.13387DOI Listing
August 2021

Differences in risk for SARS-CoV-2 infection among healthcare workers.

Prev Med Rep 2021 Dec 21;24:101518. Epub 2021 Aug 21.

Karolinska University Hospital, Stockholm SE-141 86, Sweden.

Healthcare workers (HCWs) are a risk group for SARS-CoV-2 infection, but which healthcare work that conveys risk and to what extent such risk can be prevented is not clear. Starting on April 24th, 2020, all employees at work (n = 15,300) at the Karolinska University Hospital, Stockholm, Sweden were invited and 92% consented to participate in a SARS-CoV-2 cohort study. Complete SARS-CoV-2 serology was available for n = 12,928 employees and seroprevalences were analyzed by age, sex, profession, patient contact, and hospital department. Relative risks were estimated to examine the association between type of hospital department as a proxy for different working environment exposure and risk for seropositivity, adjusting for age, sex, sampling week, and profession. Wards that were primarily responsible for COVID-19 patients were at increased risk (adjusted OR 1.95 (95% CI 1.65-2.32) with the notable exception of the infectious diseases and intensive care units (adjusted OR 0.86 (95% CI 0.66-1.13)), that were not at increased risk despite being highly exposed. Several units with similar types of work varied greatly in seroprevalences. Among the professions examined, nurse assistants had the highest risk (adjusted OR 1.62 (95% CI 1.38-1.90)). Although healthcare workers, in particular nurse assistants, who attend to COVID-19 patients are a risk group for SARS-CoV-2 infection, several units caring for COVID-19 patients had no excess risk. Large variations in seroprevalences among similar units suggest that healthcare work-related risk of SARS-CoV-2 infection may be preventable.
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http://dx.doi.org/10.1016/j.pmedr.2021.101518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379088PMC
December 2021

Antibody responses after a single dose of ChAdOx1 nCoV-19 vaccine in healthcare workers previously infected with SARS-CoV-2.

EBioMedicine 2021 Aug 12;70:103523. Epub 2021 Aug 12.

Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden. Electronic address:

Background: Recent reports demonstrate robust serological responses to a single dose of messenger RNA (mRNA) vaccines in individuals previously infected with SARS-CoV-2. Data on immune responses following a single-dose adenovirus-vectored vaccine expressing the SARS-CoV-2 spike protein (ChAdOx1 nCoV-19) in individuals with previous SARS-CoV-2 infection are however limited, and current guidelines recommend a two-dose regimen regardless of preexisting immunity.

Methods: We compared RBD-specific IgG and RBD-ACE2 blocking antibodies against SARS-CoV-2 wild type and variants of concern following two doses of the mRNA vaccine BNT162b2 in SARS-CoV-2 naïve healthcare workers (n=65) and a single dose of the adenovector vaccine ChAdOx1 nCoV-19 in 82 healthcare workers more than (n=45) and less than (n=37) 11 months post mild SARS-CoV-2 infection at time of vaccination.

Findings: The post-vaccine levels of RBD-specific IgG and neutralizing antibodies against the SARS-CoV-2 wild type and variants of concern including Delta lineage 1.617.2 were similar or higher in participants receiving a single dose of ChAdOx1 nCoV-19 vaccine post SARS-CoV-2 infection (both more than and less than 11 months post infection) compared to SARS-CoV-2 naïve participants who received two doses of BNT162b2 vaccine.

Interpretation: Our data support that a single dose ChAdOx1 nCoV-19 vaccine that is administered up to at least 11 months post SARS-CoV-2 infection serves as an effective immune booster. This provides a possible rationale for a single-dose vaccine regimen.

Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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http://dx.doi.org/10.1016/j.ebiom.2021.103523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357428PMC
August 2021

The Shrunken pore syndrome is associated with poor prognosis and lower quality of life in heart failure patients: the HARVEST-Malmö study.

ESC Heart Fail 2021 Oct 12;8(5):3577-3586. Epub 2021 Aug 12.

Department of Clinical Sciences, Lund University, Malmö, Sweden.

Aims: This study aimed to investigate the association between the 'Shrunken pore syndrome' (SPS) and risk of death, 30 day rehospitalization, and health-related quality of life (QoL) in heart failure (HF) patients. SPS is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFR /eGFR ratio.

Methods And Results: A total of 373 patients hospitalized for HF [mean age 74.8 (±12.1) years; 118 (31.6%) women] were retrieved from the HeARt and brain failure inVESTigation trial (HARVEST-Malmö). Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were used for estimation of glomerular filtration rate (eGFR). Presence of SPS was defined as eGFR  ≤ 60% of eGFR . In Cox regression multivariate models, associations between SPS, risk of death (median follow-up time 1.8 years), and risk of 30 day rehospitalization were studied. Associations between SPS and impaired QoL were studied using multivariate logistic regressions. In multivariate models, SPS was associated with all-cause mortality [124 events; hazard ratio (HR) 1.99; 95% confidence interval (95% CI) 1.23-3.21; P = 0.005] and with 30 day rehospitalization (70 events; HR 1.82; CI 95% 1.04-3.18; P = 0.036). Analyses of QoL, based on a Kansas City Cardiomyopathy Questionnaire overall score < 50, revealed that SPS was associated with higher risk of low health-related QoL (odds ratios 2.15; CI 95% 1.03-4.49; P = 0.042).

Conclusions: The results of this observational study show for the first time an association between SPS and poor prognosis in HF. Further studies are needed to confirm the results in HF cohorts and experimental settings to identify pathophysiological mechanisms.
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http://dx.doi.org/10.1002/ehf2.13485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497365PMC
October 2021

Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.

Clin Transl Immunology 2021 19;10(7):e1312. Epub 2021 Jul 19.

Department of Clinical Neuroscience Center for Molecular Medicine Karolinska Institutet Stockholm Sweden.

Objective: The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay.

Methods: More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020.

Results: Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%.

Conclusion: These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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http://dx.doi.org/10.1002/cti2.1312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288725PMC
July 2021

Metabolic factors and the risk of Dupuytren's disease: data from 30,000 individuals followed for over 20 years.

Sci Rep 2021 07 19;11(1):14669. Epub 2021 Jul 19.

Department of Hand Surgery, Lund University, Skåne University Hospital, Jan Waldenströms gata 5, 205 02, Malmö, Sweden.

Dupuytren's disease (DD) is a fibroproliferative disorder affecting the palmar fascia of the hand. Risk factors include diabetes mellitus (DM), whereas a high body mass index (BMI) is associated with a lower prevalence of DD. The aim of this study was to further elucidate risk and protective factors for the development of DD using longitudinal population-based data from the Malmö Diet and Cancer Study (MDCS). During 1991-1996, the inhabitants aged 46-73 years in the city of Malmö, Sweden were invited to participate in the population-based MDCS (41% participation rate). Data on incident DD were retrieved from Swedish national registers. Associations between DM, alcohol consumption, BMI, and serum apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) at baseline were analysed in multivariable Cox regression models adjusted for known confounders. Among 30,446 recruited participants, 347 men and 194 women were diagnosed with DD during a median follow-up time of 23 years. DM (men HR 2.23; 95% CI 1.50-3.30, women HR 2.69; 95% CI 1.48-4.90) and alcohol consumption (men HR 2.46; 95% CI 1.85-3.27, women HR 3.56; 95% CI 1.95-6.50) were independently associated with incident DD in the Cox regression models. Furthermore, inverse associations with incident DD were found for obesity among men, and ApoB/ApoA1 ratio among both sexes. DM and excess alcohol consumption constituted major risk factors for the development of DD. Furthermore, an inverse association between obesity among men and DD, and also between ApoB/ApoA1 ratio and DD was found in both sexes.
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http://dx.doi.org/10.1038/s41598-021-94025-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289914PMC
July 2021

Novel Reclassification of Adult Diabetes Is Useful to Distinguish Stages of β-Cell Function Linked to the Risk of Vascular Complications: The DOLCE Study From Northern Ukraine.

Front Genet 2021 2;12:637945. Epub 2021 Jul 2.

Department of Clinical Science, Center for Diabetes Research, University of Bergen, Bergen, Norway.

Background: Presently, persons with diabetes are classified as having type 1 (T1D) or type 2 diabetes (T2D) based on clinical diagnosis. However, adult patients exhibit diverse clinical representations and this makes treatment approaches challenging to personalize. A recent Scandinavian study proposed a novel classification of adult diabetes into five clusters based on disease pathophysiology and risk of vascular complications. The current study aimed to characterize new subgroups of adult diabetes using this strategy in a defined population from northern Ukraine.

Methods: We analyzed 2,140 patients with established diabetes from the DOLCE study ( = 887 with new-onset diabetes and = 1,253 with long duration). We used the k-means approach to perform clustering analyses using BMI, age at onset of diabetes, HbA, insulin secretion (HOMA2-B), and insulin resistance (HOMA2-IR) indices and glutamic acid decarboxylase antibodies (GADA) levels. Risks of macro- (myocardial infarction or stroke) and microvascular [retinopathy, chronic kidney disease (CKD) and neuropathy] complications and associations of genetic variants with specific clusters were studied using logistic regression adjusted for age, sex, and diabetes duration.

Results: Severe autoimmune diabetes (SAID, 11 and 6%) and severe insulin-deficient diabetes (SIDD, 25 and 14%) clusters were twice as prevalent in patients with long-term as compared to those with new-onset diabetes. Patients with long duration in both SAID and SIDD clusters had highest risks of proliferative retinopathy, and elevated risks of CKD. Long-term insulin-resistant obese diabetes 1 (IROD1) subgroup had elevated risks of CKD, while insulin-resistant obese diabetes 2 (IROD2) cluster exhibited the highest HOMA2-B, lowest HbA, and lower prevalence of all microvascular complications as compared to all other clusters. Genetic analyses of IROD2 subgroup identified reduced frequency of the risk alleles in the gene as compared to all other clusters, cumulatively and individually ( = 0.0001).

Conclusion: The novel reclassification algorithm of patients with adult diabetes was reproducible in this population from northern Ukraine. It may be beneficial for the patients in the SIDD subgroup to initiate earlier insulin treatment or other anti-diabetic modalities to preserve β-cell function. Long-term diabetes cases with preserved β-cell function and lower risk for microvascular complications represent an interesting subgroup of patients for further investigations of protective mechanisms.
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http://dx.doi.org/10.3389/fgene.2021.637945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283002PMC
July 2021

Ventricular-arterial coupling: definition, pathophysiology and therapeutic targets in cardiovascular disease.

Expert Rev Cardiovasc Ther 2021 Aug 21;19(8):753-761. Epub 2021 Jul 21.

Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.

Introduction: The heart and arterial system are equally affected by arteriosclerosis/atherosclerosis. There is a constant interaction between the left ventricular (LV) function and the arterial system, termed ventricular-arterial coupling (VAC), which reflects the global cardiovascular efficiency. VAC is traditionally assessed by echocardiography as the ratio of effective arterial elastance (E) over end-systolic elastance (E) (E/E). However, the concept of VAC is evolving and new methods have been proposed such as the ratio of pulse wave velocity (PWV) to global longitudinal strain (GLS) and myocardial work index.

Area Covered: This clinical review presents the hemodynamic background of VAC, its clinical implications and the impact of therapeutic interventions to normalize VAC. The review also summarizes the detrimental effects of cardio-metabolic risk factors on the aorta and LV, and provides an update on arterial load and its impact on LV function. The narrative review is based upon a systemic search of the bibliographic database PubMed for publications on VAC.

Expert Opinion: Newer methods such as PWV/GLS-ratio may be a superior marker of VAC than the traditional echocardiographic E/E in predicting target organ damage and its association with clinical outcomes. Novel anti-diabetic drugs and optimal antihypertensive treatment may normalize VAC in high-risk patients.
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http://dx.doi.org/10.1080/14779072.2021.1955351DOI Listing
August 2021

Perinatal famine is associated with excess risk of proliferative retinopathy in patients with type 2 diabetes.

Acta Ophthalmol 2021 Jun 24. Epub 2021 Jun 24.

Department of Clinical Science, Center for Diabetes Research, University of Bergen, Bergen, Norway.

Purpose: Intrauterine undernutrition is associated with increased risk of type 2 diabetes. Children born premature or small for gestational age were reported to have abnormal retinal vascularization. However, whether intrauterine famine act as a trigger for diabetes complications, including retinopathy, is unknown. The aim of the current study was to evaluate long-term effects of perinatal famine on the risk of proliferative diabetic retinopathy (PDR).

Methods: We studied the risk for PDR among type 2 diabetes patients exposed to perinatal famine in two independent cohorts: the Ukrainian National Diabetes Registry (UNDR) and the Hong Kong Diabetes Registry (HKDR). We analysed individuals born during the Great Famine (the Holodomor, 1932-1933) and the WWII (1941-1945) famine in 101 095 (3601 had PDR) UNDR participants. Among 3021 (251 had PDR) HKDR participants, we studied type 2 diabetes patients exposed to perinatal famine during the WWII Japanese invasion in 1942-1945.

Results: During the Holodomor and WWII, perinatal famine was associated with a 1.76-fold (p = 0.019) and 3.02-fold (p = 0.001) increased risk of severe PDR in the UNDR. The risk for PDR was 1.66-fold elevated among individuals born in 1942 in the HKDR (p < 0.05). The associations between perinatal famine and PDR remained statistically significant after corrections for HbA1c in available 18 507 UNDR (p  < 0.001) and in 3021 HKDR type 2 diabetes patients (p < 0.05).

Conclusion: In conclusion, type 2 diabetes patients, exposed to perinatal famine, have increased risk of PDR compared to those without perinatal famine exposure. Further studies are needed to understand the underlying mechanisms and to extend this finding to other diabetes complications.
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http://dx.doi.org/10.1111/aos.14948DOI Listing
June 2021

Risk of SARS-CoV-2 exposure among hospital healthcare workers in relation to patient contact and type of care.

Scand J Public Health 2021 Nov 19;49(7):707-712. Epub 2021 Jun 19.

Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.

Aim: We aimed to assess prevalence of IgG antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and factors associated with seropositivity in a large cohort of healthcare workers (HCWs).

Methods: From 11 May until 11 June 2020, 3981 HCWs at a large Swedish emergency care hospital provided serum samples and questionnaire data. Presence of IgG antibodies to SARS-CoV-2 was measured as an indicator of SARS-CoV-2 exposure.

Results: The total seroprevalence was 18% and increased during the study period. Among the seropositive HCWs, 11% had been entirely asymptomatic. Participants who worked with COVID-19 patients had higher odds for seropositivity: adjusted odds ratio 1.96 (95% confidence intervals 1.59-2.42). HCWs from three of the departments managing COVID-19 patients had significantly higher seroprevalences, whereas the prevalence among HCWs from the intensive care unit (also managing COVID-19 patients) was significantly lower.

Conclusions:
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http://dx.doi.org/10.1177/14034948211022434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521364PMC
November 2021

The association between carotid-femoral pulse-wave velocity and lung function in the Swedish CArdioPulmonary bioImage study (SCAPIS) cohort.

Respir Med 2021 Aug-Sep;185:106504. Epub 2021 Jun 9.

Department of Clinical Sciences Malmö, Lund University, Sweden. Electronic address:

Background: Arterial ageing is characterised by degradation of elastic fibres and increased stiffness of elastic arteries. Although low lung function and arterial stiffness are strongly related to age, the association between lung function and arterial ageing has not been widely explored. We used a large population-based study of 50-64 year olds to assess the association between lung function (measured by spirometry and CO diffusing capacity (D)) and arterial stiffness (measured by carotid-femoral pulse-wave velocity (c-f PWV)).

Methods: Participants from the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort with information on spirometry (n = 8941) and D (n = 8616) were included. General linear models (lung function quartiles) and linear regression was used to determine the association between lung function and c-f PWV.

Results: FEV (L), FVC (L), D (mmol/(min kPa)) and D/V (mmol/(min kPa L)) were significantly and inversely associated with c-f PWV after adjustments; mean PWV (m/s) in Q1 (highest lung function) vs Q4: FEV; 8.45 vs 8.60, p-value 0.001; FVC; 8.45 vs 8.57, p-value 0.018; D; 8.46 vs 8.60, p-value 0.002; and D/V; 8.47 vs 8.58, p-value 0.001. In sex-stratified analyses, significant findings were reflected for FEV and D in men only. The results remained significant for D in all never smokers and in all participants without COPD or airflow limitation on spirometry.

Conclusions: A reduction in spirometry and D is associated with elevated arterial stiffness in middle-aged men. A reduction in D is associated with higher c-f PWV even in never smokers and in those without COPD or airflow limitation on spirometry.
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http://dx.doi.org/10.1016/j.rmed.2021.106504DOI Listing
June 2021
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