Use of Vascular Assessments and Novel Biomarkers to Predict Cardiovascular Events in Type 2 Diabetes:The SUMMIT VIP Study

Cardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD

Replication study reveals miR-483-5p as an important target in prevention of cardiometabolic disease

BackgroundAlterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case–control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis.MethodsWe measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound.ResultsIn cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06–3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06–3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007).ConclusionmiR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease

Spotty Carotid Plaques Are Associated with Inflammation and the Occurrence of Cerebrovascular Symptoms

Background: Echolucent carotid plaques have been related to an increased risk of ischemic cerebrovascular events. The aim of the present study was to evaluate whether a new objective ultrasonographic parameter, the statistical geometric feature (SGF), reflecting spottiness of carotid plaques, can be associated with cerebrovascular symptoms and with a rupture-prone plaque phenotype. Methods: The plaques of 144 patients who underwent carotid endarterectomy were included in this study. SGF and plaque area were estimated by outlining the plaque on ultrasound (US) images. The correlation coefficient for inter- and intraobserver variability was 0.69 and 0.93, respectively. The SGF values were normalized to the degree of stenosis (SGF/DS). The plaques collected at surgery 1 day after the US were analyzed histologically, and inflammatory markers and matrix metalloproteinases (MMPs) were measured. Results: Patients with ipsilateral hemispheric symptoms had higher SGF/DS compared to patients without symptoms (0.82 [0.59–1.16] vs. 0.70 [0.56–0.89], p = 0.01). Analysis of plaque components revealed a positive correlation between SGF/DS and the percentage of the plaque area stained for lipids, macrophages, and hemorrhage. A correlation was also found between SGF/DS and plaque expression of interleukin-6, monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, vascular endothelial growth factor A, C-C motif chemokine 3 and 20, and MMP-9. An inverse correlation was found with plaque levels of osteoprotegerin. Conclusions: The present study supports the concept that spottiness is a feature of the carotid plaques rich in inflammation and can be associated with the typical phenotype of high-risk plaques

Arterial stiffness and incidence of diabetes : A population-based cohort study

Objective: Diabetes is known to be associated with increased arterial stiffness. However, the temporal association between increased carotid-femoral pulse wave velocity (c-f PWV) and diabetes is unclear. The aim of this study is to explore the relationship between arterial stiffness, as determined by c-f PWV, and incidence of diabetes. Research Design and Methods: The study population included participants from the Malmö Diet and Cancer cardiovascular cohort, using measurements from the 2007-2012 reexamination as baseline. Arterial stiffness was evaluated by measuring c-f PWV (SphygmoCor). After excluding participants with prevalent diabetes (according to measurements of fasting glucose, oral glucose tolerance tests, and physician's diagnoses), the final study population consisted of 2,450 individuals (mean age = 71.965.6 years). Incidence of diabetes was followed by linkage to local and national diabetes registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to the tertiles of c-f PWV, adjusted for potential confounders. Results: During a mean follow-up of 4.43 6 1.40 years, 68 (2.8%) participants developed diabetes. Crude incidence of diabetes (per 1,000 person-years) was 3.5, 5.7, and 9.5, respectively, for subjects in the first, second, and third tertiles of c-f PWV. After adjustment for potential confounders, the hazard ratio of diabetes was 1.00 (reference), 1.83 (95% CI 0.88-3.8), and 3.24 (95% CI 1.51-6.97), respectively, for the tertiles of c-f PWV (P for trend = 0.002). Conclusions: Increased c-fPWV is associated with increased incidence of diabetes, independent of other risk factors. These results suggest that increased arterial stiffness is an early risk marker for developing diabetes

Defined shapes of carotid artery calcifications on panoramic radiographs correlate with specific signs of cardiovascular disease on ultrasound examination

Objective: The aim was to optimize diagnostics for carotid artery calcifications (CACs) on panoramic radiographs (PRs) to identify cardiovascular disease (CVD) by investigating how 4 defined CAC shapes are associated with ultrasound (US) findings indicating CVD. Study Design: The study included 414 participants (802 neck sides) from the Malmö Offspring Dental Study, examined with PRs. The PRs were assessed for CAC shapes stratified into 4 categories: single, scattered, vessel-width defining, and vessel-outlining. The carotid arteries were examined with US for signs of CVD: the presence of plaques, largest individual area of a plaque, number of plaques, and percentage reduction of the lumen. Associations between the different CAC categories and US characteristics were analyzed. Results: All categories of CAC were significantly associated with a higher degree of US findings indicating CVD compared with no CAC (P < .001). The most significant differences were found for vessel-outlining CAC, with the mean of the largest individual plaque area of 17.9 vs 2.3 mm2, mean number of plaques 1.6 vs 0.2, and mean percentage reduction of the lumen 24.1% vs 3.5% (all P < .001). Conclusions: Independent of shape, CACs detected on PRs were associated with a higher degree of US findings of CVD. This was most pronounced for vessel-outlining CAC. With refined differential diagnostics of CACs in PRs, dentists may contribute to improved identification of patients in need of cardiovascular prevention

Acute phase proteins as prospective risk markers for arterial stiffness : The Malmö Diet and Cancer cohort

Background and objectives: Arterial stiffness plays a significant role in the development and progression of adverse cardiovascular events and all-cause mortality. This observational study aims to explore the relationship between six acute phase proteins namely, ceruloplasmin, alpha-1-antitrypsin, orosomucoid, haptoglobin, complement C3 and C-reactive protein (CRP), and carotid-femoral pulse wave velocity (c-f PWV) in a population-based cohort, and to also explore the effect of low-grade inflammation on the relationship between diabetes and c-f PWV. Method: The study consisted of participants from the Malmö Diet and Cancer study with data from baseline examinations (1991–1994) and follow-up examinations (2007–2012). Arterial stiffness was measured at follow-up by determining c-f PWV. After excluding participants with missing data, the total study population included 2338 subjects. General linear models were used to assess the relationship between baseline acute phase proteins and c-f PWV. Results: After adjusting for traditional risk factors the participants in the 4th quartile vs 1st quartile of alpha-1-antitrypsin (geometric mean: 10.32 m/s vs 10.04 m/s) (<0.05), C3 (10.35 m/s vs 10.06 m/s) (p<0.05) and CRP (10.37 m/s vs 9.96 m/s) (<0.001) showed significant association with c-f PWV. Diabetes at follow-up was also associated with high c-f PWV, however, this relationship was independent of low grade inflammation. Conclusion: Alpha-1-antitrypsin, C3 and CRP are associated with arterial stiffness. The results indicate that low grade inflammation is associated with arterial stiffness in addition to established cardiovascular risk factors

Markers of Atrial Myopathy in the General Population : Prevalence, Predictors, and Inter-Relations

BACKGROUND: Atrial myopathy refers to structural and functional cardiac abnormalities associated with atrial fibrillation and stroke, but appropriate diagnostic criteria are lacking.OBJECTIVES: This study aimed to assess prevalence, clinical correlates, and overlap between potential atrial myopathy markers.METHODS: The population-based SCAPIS (Swedish CArdioPulmonary bioImage Study) prospectively included 6,013 subjects without atrial fibrillation with 24-hour electrocardiograms. Resting electrocardiograms measuring P-wave indices were collected at 1 screening site (n = 1,201), and a random sample (n = 385) had echocardiographic left atrial volume index (LAVi). Atrial myopathy markers were defined as ≥500 premature atrial complexes/24 h, LAVi ≥34 mL/m2, P-wave duration >120 milliseconds, or P-wave terminal force in V1 >4,000 ms·s. Clinical correlates included age, sex, body mass index, height, smoking, physical activity, coronary artery disease, diabetes, systolic blood pressure, antihypertensive medication, and low education.RESULTS: Atrial myopathy was common; 42% of the sample with all diagnostic modalities available had ≥1 atrial myopathy marker, but only 9% had 2 and 0.3% had ≥3. Only P-wave duration and LAVi were correlated (ρ = 0.10; P = 0.04). Clinical correlates of premature atrial complexes, P-wave indices, and LAVi differed; current smoking (34% increase; P < 0.001), systolic blood pressure (4%/mm Hg increase; P = 0.01), diabetes (35% increase; P = 0.001), and coronary artery disease (71% increase; P = 0.003) were associated with premature atrial complexes, physical activity ≥2 h/wk was associated with increased LAVi (β-coefficient = 3.1; P < 0.0001) and body mass index was associated with P-wave duration (β-coefficient = 0.4/kg/m2; P < 0.0001).CONCLUSIONS: In the general population, indirect markers of atrial myopathy are common but only weakly correlated, and their risk factor patterns are different. More studies are needed to accurately identify individuals with atrial myopathy with diagnostic methods

The inverse association between a fish consumption biomarker with gingival inflammation and periodontitis : a population-based study

AIM: The metabolite 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) is a fatty fish-intake biomarker. We investigated the association between plasma levels of CMPF in relation to gingival inflammation and periodontitis case definition, as well as extent and severity variables. METHODS: The Malmö Offspring Study (MOS) is a population-based study, and the Malmö Offspring Dental Study (MODS) is its dental arm, including periodontal charting. Plasma CMPF was measured using liquid chromatography-mass spectrometry and studied in relation to periodontal diagnosis and parameters using multivariable linear or logistic regression modelling adjusting for age, sex, education, BMI, fasting glucose and smoking. RESULTS: Metabolite data were available for 922 MODS participants. Higher CMPF levels were associated with less gingival inflammation (beta -2.12, p=0.002), and lower odds of severe periodontitis (OR 0.74, 95% CI=0.56-0.98). Higher CMPF levels were also associated with more teeth (beta 0.19, p=0.001), lower number of periodontal pockets (&gt;4 mm) (beta -1.07, p=0.007) and lower odds of having two or more &gt;6 mm periodontal pockets (OR 0.80, 95% CI=0.65-0.98) in fully adjusted models. CONCLUSION: CMPF, a validated biomarker of fatty fish consumption, is associated with less periodontal inflammation and periodontitis. Residual confounding cannot be ruled out and future studies are warranted. This article is protected by copyright. All rights reserved

Relationships between the acute-phase proteins and c-f PWV.

<p>Relationships between the acute-phase proteins and c-f PWV.</p