Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes

Abstract

BackgroundActivation 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.MethodsRenin 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).ResultsPlasma 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.ConclusionsOur findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.

Associations between glycaemic control and activation of the renin-angiotensin-aldosterone system in participants with type 2 diabetes mellitus and hypertension

“…This confirms the findings of Gonc¸laves et al 34 who demonstrated an association between HbA 1c and renin measured using a different platform. Unlike these authors, we did not find an association between age, BMI, SBP, cholesterol or eGFR and renin.…”

“…31 GPR91 is highly expressed in the kidney and activation of this receptor triggers paracrine signalling, resulting in renin release; this suggests that there may be a direct link between hyperglycaemia and renin release from the juxtaglomerular apparatus (JGA); [31][32][33] as glycaemic control decreases renin increases. 32 Gonc¸alves et al 34 demonstrated that there is an association between HbA 1c and renin (r ¼ 0.20 [0.14-0.26]) measured using the proximity extension assay technique. Renin converts angiotensinogen into angiotensin I (ANG I).…”

Metabolic Syndrome among Ischaemic Stroke Patients in Ghana: The Possible Role of Renin and Aldosterone

“…Concordance with this study, multivariate logistic regression analysis in a cross-sectional study showed that high PRA was independently associated high HDL-C [43]. Another cross-sectional study in 985 subjects with metSyn and 515 without metSyn showed that renin levels increased and correlated inversely with HDL [44]. Conversely, in a [45].…”

Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins

“…A survey of the literature suggests that of the 30 changes specific for SPS, 18 promote, or are associated with, atherosclerosis38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 (Table 2). The same is true for 12 of the 31 changes occurring in patients with both SPS and reduced GFR60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 and for 10 of the 27 changes specific for reduced mGFR72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84 (Table 2). These results are compatible with the observations that the majority of the causes of morbidity and death in both patients with SPS and/or reduced GFR represent manifestations of cardiovascular disorders 6, 7, 8, 9, 14.…”