Amra Jujic

Low Plasma Level of Atrial Natriuretic Peptide Predicts Development of Diabetes: The Prospective Malmo Diet and Cancer Study.

CONTEXT The cardiac natriuretic peptides are involved in blood pressure regulation, and large cross-sectional studies have shown lower plasma levels of N-terminal pro-natriuretic peptide levels [N-terminal atrial natriuretic peptide (N-ANP) and N-terminal brain natriuretic peptide (N-BNP)] in patients with insulin resistance, obesity, and diabetes. OBJECTIVE In this study, we prospectively tested whether plasma levels of mid-regional ANP (MR-ANP) and N-BNP predict new-onset diabetes and long-term glucose progression. DESIGN, SETTING, AND PATIENTS MR-ANP and N-BNP were measured in 1828 nondiabetic individuals of the Malmö Diet and Cancer cohort (mean age 60 yr; 61% women) who subsequently underwent a follow-up exam including an oral glucose tolerance test after a median follow-up time of 16 yr. Logistic regression was used to adjust for covariates. RESULTS During follow-up, 301 subjects developed new-onset diabetes. After full multivariate adjustment, MR-ANP was significantly inversely associated with incident diabetes (OR = 0.85; 95% CI = 0.73-0.99; P = 0.034) but not N-BNP (OR = 0.92; 95% CI = 0.80-1.06; P = 0.262). In fully adjusted linear regression models, the progression of fasting glucose during follow-up was significantly inversely related to baseline levels of MR-ANP (P = 0.004) but not N-BNP (P = 0.129). Quartile analyses revealed that the overall association was mainly accounted for by excess risk of incident diabetes in subjects belonging to the lowest quartile of MR-ANP. After full adjustment, the odds ratio for incident diabetes in the bottom compared with the top quartile of MR-ANP was 1.65 (OR = 1.08-2.51, P = 0.019) and 1.43 (OR = 1.04-1.96, P = 0.027) compared with all other subjects. CONCLUSION Low plasma levels of MR-ANP predict development of future diabetes and glucose progression over time, suggesting a causal role of ANP deficiency in diabetes development.

Atrial natriuretic Peptide and type 2 diabetes development - biomarker and genotype association study.

Background We have recently shown that low plasma levels of mid-regional atrial natriuretic peptide (MR-ANP) predict development of diabetes and glucose progression over time, independently of known risk factors for diabetes development. However, since MR-ANP levels might be influenced by unknown factors causing diabetes, we cannot rule out that such relationship might be confounded. Previous studies have shown an association of a single nucleotide polymorphism rs5068 on the natriuretic peptide precursor A (NPPA) locus gene with higher levels of circulating ANP. Since gene variants are inherited randomly and not subject to confounding, we aimed to investigate whether the variant rs5068 within the NPPA locus is associated with incident type 2 diabetes. Methods We genotyped the variant rs5068 within the NPPA locus in 27,307 individuals without known diabetes from the Malmö Diet Cancer Study. Incident diabetes was retrieved through national and regional registers (median follow-up time of 14 years, 2,823 incident diabetes cases). Results In Cox regression analysis adjusted for age, sex and BMI, we found that the carriers of at least one copy of the G allele of rs5068 had lower likelihood of incident diabetes within 14 years (HR = 0.88, 95% CI 0.78–0.99, p = 0.037). Conclusion Our results indicate a role of the ANP system in the etiology of type 2 diabetes and might help provide insight in the metabolic actions of natriuretic peptides and the pathophysiology of type 2 diabetes.

Orthostatic Hypotension and Cardiac Changes After Long-Term Follow-Up

BACKGROUND Orthostatic hypotension (OH) increases the risk of incident cardiovascular disease (CVD) and all-cause mortality in population-based cohort studies. Whether OH is associated with development of cardiac anomalies has not been sufficiently explored. METHODS In the prospective population-based Malmö Preventive Project (MPP), a subset of 974 non-diabetic individuals (mean age: 67 years; 29% women) were examined with echocardiography after a mean follow-up period of 23±4 years from baseline. The association of increased left ventricular mass (LVM), pathological cardiac chamber volumes, echocardiographic parameters of systolic and diastolic dysfunction in relation to the presence of OH at baseline, defined as decrease in systolic ≥20mm Hg and/or diastolic blood pressure (BP) ≥10mm Hg upon standing, was studied. RESULTS Among reexamined MPP participants, 40 (4.1%) met OH criteria during baseline screening. In the multivariable-adjusted Cox proportional hazard models, taking demographics, BP, and antihypertensive treatment (AHT) into account, OH predicted left ventricular hypertrophy (LVH) (hazard ratio (HR): 1.97, 1.01-3.84; P = 0.047), decreased right chamber volume (HR: 1.74, 1.19-2.57; P = 0.005), and reduced early diastolic tissue velocity in septal wall (HR: 1.47, 1.01-2.14; P = 0.045). No significant associations were seen between OH and atrial chamber volumes, LV volume, and LV systolic function. CONCLUSIONS The presence of OH among middle-aged adults is associated with the development of structural cardiac changes such as LVH and declining right chamber volume, as well as with the development of diastolic dysfunction, independently of traditional risk factors. These findings may contribute to the understanding of how prevalent OH impacts the risk of CVD.

Atrial Natriuretic Peptide in the High Normal Range Is Associated With Lower Prevalence of Insulin Resistance

In 2243 subjects, MR-proANP was measured at baseline. At follow up, MR-proANP levels in the high normal range were associated with lower prevalence of insulin resistance and higher post challenge GIP secretion.

The shrunken pore syndrome is associated with declined right ventricular systolic function in a heart failure population – the HARVEST study

Abstract The 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 used four different formulas for estimated glomerular filtration rate (eGFR); CKD-EPIcreatinine, CKD-EPIcystatin C, LMrev and CAPA. Presence of the syndrome was defined as eGFR cystatin C ≤ 60% of eGFR creatinine and absence of the syndrome as eGFR cystatin C >90% and <110% of eGFR creatinine. In a linear regression model, adjusted for age and sex, and the ‘Shrunken pore syndrome’ defined by the equation pair CAPA and LMrev and the equation pair CKD-EPIcystatin C and CKD-EPIcreatinine, echocardiographic parameters were studied. The ‘Shrunken pore syndrome’ showed statistically significant associations with measurements of right ventricular (RV) systolic function; (TAPSE and RV S’) (according to the equation pair CKD-EPIcystatin C and CKD-EPIcreatinine). 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’.

Segmentation of B-mode cardiac ultrasound data by Bayesian Probability Maps

In this paper we present a model for describing the position distribution of the endocardium in the two-chamber apical long-axis view of the heart in clinical B-mode ultrasound cycles. We propose a novel Bayesian formulation, including priors for spatial and temporal smoothness, and preferred shapes and position. The shape model takes into account both endocardium, atrial region and apex. The likelihood is built using a statistical signal model, which attempts to closely model a censored signal. In addition, the use of a censored Gamma mixture model with unknown censoring point, to handle artefacts resulting from left-censoring of the in US clinical B-mode, is to our knowledge novel. The posterior density is sampled by the Gibbs method to estimate the expected latent variable representation of the endocardium, which we call the Bayesian Probability Map; the map describes the probability of pixels being classified as being within the endocardium. The regularization parameters of the model are estimated by cross-validation, and the results are compared against the two-chamber apical model of Chen et al.

Autonomic dysfunction is associated with cardiac remodelling in heart failure patients

Orthostatic 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.

PS 05-68 NO CROSS-SECTIONAL ASSOCIATION FOUND BETWEEN SKIN ADVANCED GLYCATION END PRODUCTS (AGE) AND ARTERIAL STIFFNESS IN A NON-HOSPITALIZED ELDERLY POPULATION

Objective: Evaluation of transdermal Advanced Glycation End (AGE) products autofluorescence (skin-AF) is a new method for estimation of exposure to hyperglycaemia and oxidative stress. Previous studies have shown that skin-AF is elevated in patients with some chronic disease conditions (End-stage renal disease, ESRD; type-1 diabetes) and atherosclerosis, but population-based data on the association with arteriosclerosis (arterial stiffness) are sparse. Design and Method: We examined a total of 498 elderly subjects (mean age 72 years, 39% men) from the Malmö Diet Cancer–Cardiovascular cohort during 2007–2012. Methods included measurement of skin-AF (AgeReader®, Diagnoptics) and assessment by carotid-femoral pulse wave velocity, (c-f PWV) (SphygmoCor®, AtCor Medical), in addition to a number of lab-analyses and data on medical history. Subjects with arrhythmias were excluded for technical reasons. Results: Skin-AF correlated significantly with c-f PWV (r = 0.13, p = 0.005), but after adjustment for chronological age, mean arterial pressure (MAP), and heart rate (HR), this became a non-significant trend (&bgr; = 0.07, p = 0.08). Further adjustment also for sex, diabetes, renal function and antihypertensive drug treatment resulted in non-significant findings (&bgr; = 0.02, p > 0.5). The adjusted associations between skin-AF and c-f PWV were non-significant in subjects with and without diabetes and in both sexes. In older subjects (>72 years, median) a positive correlation was seen (r = 0.164, p = 0.009), but became non-significant following adjustments. In subjects with normoglycaemia, a positive correlation was found (r = 0.225, p = 0.023), but was lost following full adjustment. Conclusions: Skin-AF for AGE is not significantly associated with measures of arterial stiffness (c-f PWV) in a non-hospitalized elderly population following adjustments. This could indicate that such associations could be different from that seen in patients with chronic disease or atherosclerosis, or that skin-AF mirrors oxidative stress exposure of greater relevance for atherosclerosis (intima) than arteriosclerosis (media).