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

Hypothesis-driven clinical study to see if plasma renin levels are associated with the severity of vascular complications in subjects with or wthout type II diabetes (T2D). Based on earlier proposals that activation of the renin-angiotensin-aldersterone-system (RAAS) may contribute to atherosclerotic events in T2D, and aiming to use renin as marker for this pathway. This was a large study using the SUMMIT cohort (http://www.imi-summit.eu), examining 985 subjects with, and 515 without T2D. Both of these groups were sub-divided into subjects with or without CVD. Used CVD I panel to examine the plasma levels of renin, and assess the data in relation to physical biological parameters (e.g. ankle-brachial pressure index, carotid plaque area) and relevant co-variants (e.g. BMI, age, HDL levels). The key fiding was that renin levels were significantly higher in T2D subjects, and that subjects with prevelant CVD had increased renin in both the T2D and non-T2D groups. Further analysis of the data taking account of known CVD risk factors used in the Framingham risk score (age, gender, smoking, cholesterol levels and blood pressure) established that the association of renin levels with CVD was independent of these known risk factors. The renin association with these and other risk factors was equally strong in the T2D and non-T2D groups, with the exception of an inverse correlation to systolic blood pressure that was only seen in T2D subjects. The only other marker from the CVD I panel mentioned in the study was IL-6, which they used as a marker for inflammation, and which was positively associated with renin levels in the T2D and non-T2D groups. When they looked at severity of atherosclerosis, they saw a clear association with renin levels that was seen with or without T2D, and was independent of associated risk factors. When looking more closely into atherosclerotic plaques, plasma renin levels showed a weak correlation to the PDGF and TNF-alpha content of the plaques, but not to other structural markers such as elastin, collagen or macrophages. They then used Proseek to examine renin levels in both plasma and plaque homogenates obtained from a separate group of 205 carotid endarterectomy patients. The plasma renin levels of these patients correlated strongly with those obtained from plaque tissue (indicating that the plasma measurements are a good reflection of what was happening locally in the plaques, and showing the strength of Proseek in addressing very different sample types). Their conclusion was that they obtained clinical evidence for an association between RAAS activation (as measured by renin levels) and atherosclerotic burden in patients with or without T2D. The concomitant increase in renin and atherosclerosis in T2D patients compared to matched controls suggests that this association may be of particular importance in the vascular complications seen in diabetes. One observation that remains to be properly explained, however, is that treatment with RAAS pathway inhibitors (e.g. ACE inhibitors) seems to have very little effect on the atherogenic effects of RAAS activation.