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.

As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18–71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.

The shrunken pore syndrome is associated with declined right ventricular systolic function in a heart failure population -the HARVEST study Christensson, Anders; Grubb, Anders; Molvin, John; Holm, Hannes; Gränsbo, Klas; Tasevska-Dinevska, Gordana; Bachus, Erasmus; Jujic, Amra; Magnusson, Martin Christensson, A., Grubb, A., Molvin, J., Holm, H., GRÄNSBO, K. L. A. S., Tasevska-Dinevska, G., ... Magnusson, M. (2016). The shrunken pore syndrome is associated with declined right ventricular systolic function in a heart failure population -the HARVEST study. Scandinavian Journal of Clinical & Laboratory Investigation, 76(7), 568-574. DOI: 10.1080DOI: 10. /00365513.2016 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal 1The Shrunken pore syndrome is associated with declined right ventricular systolic function in a heart failure population -the HARVEST study AbstractThe close relationship between heart and kidney diseases was studied with respect to the "Shrunken pore syndrome" that is characterized by a difference in renal filtration between cystatin C and creatinine. Patients were retrieved from the HeARt and brain failure inVESTigation trail (HARVEST) which is an ongoing study undertaken in individuals hospitalized for the diagnosis of heart failure. Ninety-five of 116 patients who underwent transthoracic echocardiograms (TTE) were eligible for this study. We In conclusion, heart failure patients with the "Shrunken pore syndrome" are at increased risk of having RV systolic dysfunction whilst heart failure patients without "Shrunken pore syndrome" seem protected. These findings may indicate common pathophysiological events in the kidneys and the heart explaining the observed increased risk of mortality in subjects with the "Shrunken pore syndrome".3

Multiplex proteomic platforms provide excellent tools for investigating associations between multiple proteins and disease (e.g., diabetes) with possible prognostic, diagnostic, and therapeutic implications. In this study our aim was to explore novel pathophysiological pathways by examining 92 proteins and their association with incident diabetes in a population-based cohort (146 cases of diabetes versus 880 controls) followed over 8 years. After adjusting for traditional risk factors, we identified seven proteins associated with incident diabetes. Four proteins (Scavenger receptor cysteine rich type 1 protein M130, Fatty acid binding protein 4, Plasminogen activator inhibitor 1 and Insulin-like growth factor-binding protein 2) with a previously established association with incident diabetes and 3 proteins (Cathepsin D, Galectin-4, Paraoxonase type 3) with a novel association with incident diabetes. Galectin-4, with an increased risk of diabetes, and Paraoxonase type 3, with a decreased risk of diabetes, remained significantly associated with incident diabetes after adjusting for plasma glucose, implying a glucose independent association with diabetes.

Aims We aimed to search for associations between cognitive test results with mortality and rehospitalization in a Swedish prospective heart failure (HF) patient cohort. Methods and results Two hundred and eighty-one patients hospitalized for HF (mean age, 74 years; 32% women) were assessed using cognitive tests: Montreal Cognitive Assessment (MoCA), A Quick Test of Cognitive speed, Trail Making Test A, and Symbol Digit Modalities Test. The mean follow-up time censored at rehospitalization or death was 13 months (interquartile range, 14) and 28 months (interquartile range, 29), respectively. Relations between cognitive test results, mortality, and rehospitalization risk were analysed using multivariable Cox regression model adjusted for age, sex, body mass index, systolic blood pressure, atrial fibrillation, diabetes, smoking, educational level, New York Heart Association class, and prior cardiovascular disease. A total of 80 patients (29%) had signs of cognitive impairment (MoCA score < 23 points). In the fully adjusted Cox regression model using standardized values per 1 SD change of each cognitive test, lower score on MoCA [hazard ratio (HR), 0.75; confidence interval (CI), 0.60-0.95; P = 0.016] and Symbol Digit Modalities Test (HR, 0.66; CI, 0.48-0.90; P = 0.008) yielded significant associations with increased mortality. Rehospitalization risk (n = 173; 62%) was significantly associated with lower MoCA score (HR, 0.84; CI, 0.71-0.99; P = 0.033). Conclusions Two included cognitive tests were associated with mortality in hospitalized HF patients, independently of traditional risk factors. In addition, worse cognitive test scores on MoCA heralded increased risk of rehospitalization.

ObjectivesIn 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.MethodsBio-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).ResultsPenKid 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).ConclusionIn 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.

AimsOrthostatic hypotension (OH) is a cardinal sign of autonomic dysfunction and a common co‐morbidity in heart failure (HF). The role of autonomic dysfunction in the development of structural cardiac anomalies in HF patients has not been sufficiently explored. We aimed to assess relations between orthostatic blood pressure (BP) responses during active standing and echocardiographic changes in a series of patients admitted for HF.Methods and resultsOne hundred and forty‐nine patients hospitalized for HF [mean age: 74 years; 30% women; ejection fraction (LVEF) 40 ± 16%] were examined with conventional echocardiograms and active‐standing test. Associations of cardiac remodelling parameters with the difference between supine and standing (after 3 min) systolic/diastolic BP were examined. Systolic BP decreased (−1.1 ± 15 mmHg), whereas diastolic BP increased (+1.0 ± 9.5 mmHg) after 3 min of active standing. A total of 34 patients (23%) met conventional OH criteria; i.e. systolic/diastolic BP decreases by ≥20/10 mmHg. In the multivariable linear regression analysis, adjusted for traditional cardiovascular risk factors and LVEF, a decrease in systolic BP upon standing was associated with greater left atrial volume [β per −10 mmHg: 2.37, standard error (SE) = 1.16, P = 0.043], and greater left ventricular mass (β per −10 mmHg: 5.67, SE = 2.24, P = 0.012), but not with other echocardiographic parameters. No significant associations were observed between signs of cardiac remodelling and decrease in diastolic BP.ConclusionsOrthostatic decrease in systolic BP among older HF patients is associated with structural cardiac changes such as increased left atrial volume and left ventricular mass, independently of traditional risk factors and left ventricular dysfunction.

Purpose:The "Shrunken pore syndrome" (SPS) is characterized by a difference in renal filtration between cystatin C and creatinine, resulting in a low eGFR cystatinC /eGFR creatinine -ratio. Studies have demonstrated a high risk for cardiovascular morbidity and mortality for patients with SPS. In this discovery study, we explored associations between SPS and proteins implicated in cardiovascular disease and inflammation in patients with heart failure. Experimental Design: Plasma samples from 300 individuals in HARVEST-Malmö trial hospitalized for the diagnosis of heart failure (mean age 74.9 ± 11.5 years; 30.0% female), were analyzed with a proximity extension assay consisting of 92 proteins. A Bonferroni-corrected p-value of 0.05/92 = 5.4 × 10 −4 was considered significant in the initial age and sex-adjusted analyses. Presence of SPS was defined as eGFR cystatinC ≤ 60% of eGFR creatinine .Results: SPS presented with significant associations (p < 5.4 × 10 −4 ) in age and sexadjusted logistic regressions with elevated levels of six proteins; scavenger receptor cysteine rich type 1 protein M130, tumor necrosis factor receptor 1, tumor necrosis factor receptor 2, osteoprotegerin, interleukin-2 receptor subunit alpha, and tyrosineprotein kinase receptor UFO. All proteins remained associated (p < 0.05) with SPS after multivariate adjustments. Conclusions and clinical relevance:In heart failure patients, SPS was associated with proteins linked to atherosclerosis and cell proliferation.