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| 2. |
- Aizawa, Kunihiko, et al.
(författare)
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Reservoir Pressure Integral Is Independently Associated With the Reduction in Renal Function in Older Adults
- 2022
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Ingår i: Hypertension. - 0194-911X. ; 79:10, s. 2364-2372
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Tidskriftsartikel (refereegranskat)abstract
- Background: Arterial hemodynamic parameters derived from reservoir-excess pressure analysis exhibit prognostic utility. Reservoir-excess pressure analysis may provide useful information about an influence of altered hemodynamics on target organ such as the kidneys. We determined whether the parameters derived from the reservoir-excess pressure analysis were associated with the reduction in estimated glomerular filtration rate in 542 older adults (69.4±7.9 years, 194 females) at baseline and after 3 years. Methods: Reservoir-excess pressure parameters, including reservoir pressure integral, excess pressure integral, systolic, and diastolic rate constants, were obtained by radial artery tonometry. Results: After 3 years, and in a group of 94 individuals (72.4±7.6 years, 26 females), there was an estimated glomerular filtration rate reduction of >5% per year (median reduction of 20.5% over 3 years). A multivariable logistic regression analysis revealed that higher baseline reservoir pressure integral was independently associated with a smaller reduction in estimated glomerular filtration rate after accounting for conventional cardiovascular risk factors and study centers (odds ratio: 0.660 [95% CIs, 0.494-0.883]; P=0.005). The association remained unchanged after further adjustments for potential confounders and baseline renal function (odds ratio: 0.528 [95% CIs, 0.351-0.794]; P=0.002). No other reservoir-excess pressure parameters exhibited associations with the reduction in renal function. Conclusions: This study demonstrates that baseline reservoir pressure integral was associated with the decline in renal function in older adults at 3-year follow-up, independently of conventional cardiovascular risk factors. This suggests that reservoir pressure integral may play a role in the functional decline of the kidneys.
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| 3. |
- Aizawa, Kunihiko, et al.
(författare)
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Type 2 diabetes exacerbates changes in blood pressure-independent arterial stiffness : cross-sectional and longitudinal evidence from the SUMMIT study
- 2024
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Ingår i: Journal of Applied Physiology. - 8750-7587. ; 136:1, s. 13-22
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Tidskriftsartikel (refereegranskat)abstract
- Greater central artery stiffness is observed in people with type 2 diabetes (T2DM). Elevated blood pressure (BP) and altered arterial wall structure/composition in T2DM are generally considered as main drivers for this alteration. However, because conventional arterial stiffness measures are BP-dependent and as such an influence of BP remains in a measure, it is unclear if greater central artery stiffness is a function of greater BP, or due to changes in the structure and composition of the arterial wall. We aimed to measure BP-independent arterial stiffness (b0) cross-sectionally and longitudinally in T2DM. We studied 753 adults with T2DM (DM þ) and 436 adults without (DM-) at baseline (Phase 1), and 310 DM þ and 210 DM- adults at 3-yr follow-up (Phase 2). We measured carotid-femoral pulse wave velocity and used it to calculate b0. In Phase 1, b0 was significantly greater in DM þ than DM- after adjusting for age and sex [27.5 (26.6–28.3) vs. 23.6 (22.4–24.8) au, P < 0.001]. Partial correlation analyses after controlling for age and sex showed that b0 was significantly associated with hemoglobin A1c (r ¼ 0.15 P < 0.001) and heart rate [(HR): r ¼ 0.23 P < 0.001)] in DM þ . In Phase 2, percentage-change in b0 was significantly greater in DM þ than DM-[19.5 (14.9–24.0) vs. 5.0 (-0.6 to 10.6) %, P < 0.001] after adjusting for age, sex, and baseline b0. b0 was greater in DM þ than DM- and increased much more in DM þ than in DM- over 3 yr. This suggests that T2DM exacerbates BP-independent arterial stiffness and may have a complemental utility to existing arterial stiffness indices. NEW & NOTEWORTHY We demonstrate in this study a greater BP-independent arterial stiffness b0 in people with type 2 diabetes (T2DM) compared to those without, and also a greater change in b0 over 3 yr in people with T2DM than those without. These findings suggest that the intrinsic properties of the arterial wall may change in a different and more detrimental way in people with T2DM and likely represents accumulation of cardiovascular risk.
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| 4. |
- Fabiani, Iacopo, et al.
(författare)
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Imaging of the vulnerable carotid plaque : Role of imaging techniques and a research agenda
- 2020
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Ingår i: Neurology. - 1526-632X. ; 94:21, s. 922-932
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVES: Atherothrombosis in the carotid arteries is a main cause of ischemic stroke and may depend on plaque propensity to complicate with rupture or erosion, in turn related to vulnerability features amenable to in vivo imaging. This would provide an opportunity for risk stratification and-potentially-local treatment of more vulnerable plaques. We here review current information on this topic. METHODS: We systematically reviewed the literature for concepts derived from pathophysiologic, histopathologic, and clinical studies on imaging techniques attempting at identifying vulnerable carotid lesions. RESULTS: Ultrasound, MRI, CT, and nuclear medicine-based techniques, alone or with multimodality approaches, all have a link to pathophysiology and describe different-potentially complementary-aspects of lesions prone to complications. There is also, however, a true paucity of head-to-head comparisons of such techniques for practical implementation of a thorough and cost-effective diagnostic strategy based on evaluation of outcomes. Especially in asymptomatic patients, major international societies leave wide margins of indecision in the advice to techniques guiding interventions to prevent atherothrombotic stroke. CONCLUSIONS: To improve practical management of such patients-in addition to the patient's vulnerability for systemic reasons-a more precise identification of the vulnerable plaque is needed. A better definition of the diagnostic yield of each imaging approach in comparison with the others should be pursued for a cost-effective translation of the single techniques. Practical translation to guide future clinical practice should be based on improved knowledge of the specific pathophysiologic correlates and on a comparative modality approach, linked to subsequent stroke outcomes.
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| 5. |
- Gargani, Luna, et al.
(författare)
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Detecting the vulnerable carotid plaque : The Carotid Artery Multimodality imaging Prognostic study design
- 2022
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Ingår i: Journal of Cardiovascular Medicine. - 1558-2027. ; 23:7, s. 466-473
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCarotid artery disease is highly prevalent and a main cause of ischemic stroke and vascular dementia. There is a paucity of information on predictors of serious vascular events. Besides percentage diameter stenosis, international guidelines also recommend the evaluation of qualitative characteristics of carotid artery disease as a guide to treatment, but with no agreement on which qualitative features to assess. This inadequate knowledge leads to a poor ability to identify patients at risk, dispersion of medical resources, and unproven use of expensive and resource-consuming techniques, such as magnetic resonance imaging, positron emission tomography, and computed tomography.ObjectivesThe Carotid Artery Multimodality imaging Prognostic (CAMP) study will: prospectively determine the best predictors of silent and overt ischemic stroke and vascular dementia in patients with asymptomatic subcritical carotid artery disease by identifying the noninvasive diagnostic features of the 'vulnerable carotid plaque'; assess whether 'smart' use of low-cost diagnostic methods such as ultrasound-based evaluations may yield at least the same level of prospective information as more expensive techniques.Study designWe will compare the prognostic/predictive value of all proposed techniques with regard to silent or clinically manifest ischemic stroke and vascular dementia. The study will include ≥300 patients with asymptomatic, unilateral, intermediate degree (40-60% diameter) common or internal carotid artery stenosis detected at carotid ultrasound, with a 2-year follow-up. The study design has been registered on Clinicaltrial.gov on December 17, 2020 (ID number NCT04679727).
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| 6. |
- Gonçalves, Isabel, et al.
(författare)
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Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes
- 2016
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 16:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D. Methods: Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI). Results: Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients. Conclusions: Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.
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| 7. |
- Goncalves, Isabel, et al.
(författare)
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Elevated Plasma Levels of MMP-12 Are Associated With Atherosclerotic Burden and Symptomatic Cardiovascular Disease in Subjects With Type 2 Diabetes.
- 2015
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 35:7, s. 1723-1731
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and play important roles in development and tissue repair. They have also been shown to have both protective and pathogenic effects in atherosclerosis, and experimental studies have suggested that MMP-12 contributes to plaque growth and destabilization. The objective of this study was to investigate the associations between circulating MMPs, atherosclerosis burden, and incidence of cardiovascular disease with a particular focus on type 2 diabetes mellitus.
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| 8. |
- Khan, Faisel, et al.
(författare)
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Plaque characteristics and biomarkers predicting regression and progression of carotid atherosclerosis
- 2022
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Ingår i: Cell Reports Medicine. - : Elsevier BV. - 2666-3791. ; 3:7
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Tidskriftsartikel (refereegranskat)abstract
- The factors that influence the atherosclerotic disease process in high-risk individuals remain poorly understood. Here, we used a combination of vascular imaging, risk factor assessment, and biomarkers to identify factors associated with 3-year change in carotid disease severity in a cohort of high-risk subjects treated with preventive therapy (n = 865). The results show that changes in intima-media thickness (IMT) are most pronounced in the carotid bulb. Progression of bulb IMT demonstrates independent associations with baseline bulb IMT, the plaque gray scale median (GSM), and the plasma level of platelet-derived growth factor (PDGF) (standardized β-coefficients and 95% confidence interval [CI] −0.14 [−0.06 to −0.02] p = 0.001, 0.15 [0.02–0.07] p = 0.001, and 0.20 [0.03–0.07] p < 0.001, respectively). Plasma PDGF correlates with the plaque GSM (0.23 [0.15–0.29] p < 0.001). These observations provide insight into the atherosclerotic process in high-risk subjects by showing that progression primarily occurs in fibrotic plaques and is associated with increased levels of PDGF.
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| 9. |
- Kozakova, Michaela, et al.
(författare)
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Cardiovascular organ damage in type 2 diabetes mellitus : The role of lipids and inflammation
- 2019
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between dyslipidemia, inflammation and CV organ damage in type 2 diabetes mellitus (T2DM) is complex. Insulin resistance and inflammatory cytokines interleukins (ILs) increase plasma triglycerides (TG). ILs also up-regulate expression of matrix-metalloproteinases (MMPs) that, together with TG, decrease high density lipoprotein cholesterol (HDL) levels. High TG, low HDL, increased ILs and MMPs trigger structural and functional changes in different parts of cardiovascular (CV) system. To understand better the role of lipids and inflammation in CV organ damage, the present study investigated the inter-relationships between lipids, ILs and MMPs, as well as the associations of lipids, ILs and MMPs with various CV measures, both in diabetic and non-diabetic population (nonT2DM). Methods: In T2DM patients (N = 191) and nonT2DM subjects (N = 94) were assessed carotid intima-media thickness (cIMT) and inter-adventitial diameter (IADiam), carotid wave speed (ccaWS), carotid-femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, LV systolic (s′) and early diastolic (e′) longitudinal velocities of mitral annulus, together with glycemic control, lipid profile, IL-6, IL-18 and MMP-12. Results: T2DM patients, as compared to nonT2DM subjects, had significantly higher plasma levels of IL-6, IL-18, MMP-12 and lower HDL (P < 0.05-0.0001). They had also higher cIMT, IADiam, ccaWS, cfPWV and LV mass, and lower e′ velocity (P < 0.005-0.0001). Both in T2DM patients and nonT2DM subjects, MMP-12 increased with IL-6 (r = 0.43 and 0.39; P < 0.0001) and IL-18 (r = 0.32 and 0.42; P < 0.0001), and HDL decreased with MMP-12 (r = - 0.29 and - 0.42; P < 0.0001). In both populations, MMP-12 was directly associated with IADiam, ccaWS, cfPWV and LV mass (r = 0.42, 0.32, 0.26 and 0.29; P < 0.0001 in T2DM patients, and r = 0.39, 0.28, 0.32 and 0.27; P < 0.01-0.0001 in nonT2DM subjects). In multivariate analysis, MMP-12 remained independently related to IADiam, ccaWS, cfPWV and LV mass in T2DM patients, and to IADiam only in nonT2DM subjects. Conclusions: This cross-sectional study demonstrated a direct association between ILs and MMP-12, as well as an inverse association between MMP-12 and HDL, both in T2DM patients and in nonT2DM subjects. In T2DM patients, who had higher levels of ILs and MMP-12, the latter was independently related to several structural and functional markers of preclinical CV organ damage.
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| 10. |
- Kozakova, Michaela, et al.
(författare)
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Gamma-glutamyltransferase, arterial remodeling and prehypertension in a healthy population at low cardiometabolic risk
- 2020
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Ingår i: Journal of Human Hypertension. - : Springer Science and Business Media LLC. - 1476-5527 .- 0950-9240.
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Tidskriftsartikel (refereegranskat)abstract
- Plasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy subjects at low cardiometabolic risk, the associations of plasma GGT with carotid artery intima-media thickness (IMT), luminal diameter and prehypertension; in 154 subjects was evaluated also the association with aortic stiffness (cfPWV). Associations were controlled for insulin sensitivity, C-reactive protein, and life-style habits. In the main population, BP was remeasured after 3 years. Carotid diameter and cfPWV, but not IMT, were directly and independently related to plasma GGT. Subjects with prehypertension (N = 330) had higher GGT as compared with subjects with normal BP (22 [14] vs 17 [11] IU/L; adjusted P = 0.001), and within prehypertensive subjects, those who developed hypertension during 3 years had higher GGT than those without incident hypertension (27 [16] vs 21 [14] IU/L; adjusted P < 0.05). Within subjects with arterial stiffness measurement, those with prehypertension (N = 79) had higher both GGT and arterial stiffness (25 [14] vs 16 [20] IU/L and 9.11 ± 1.24 vs 7.90 ± 0.94 m/s; adjusted P < 0.01 and <0.05). In the view of previous evidence linking plasma GGT concentration to the level of systemic oxidative stress, our findings suggest a role of oxidative stress in subclinical arterial damage and in prehypertension, even in healthy subjects free of cardiometabolic risk. Arterial organ damage may represent the link between GGT and hypertension.
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