We are analyzing https://link.springer.com/article/10.1007/s00125-004-1510-8.

Title:
Spironolactone impairs endothelial function and heart rate variability in patients with Type 2 diabetes | Diabetologia
Description:
Aims/hypothesis Aldosterone blockade has followed in the footsteps of ACE inhibition in reducing mortality in patients with heart failure. This is associated with its beneficial effects on endothelial function and heart rate variability. Diabetes is another area, where angiotensin II withdrawal has proven to be of particular value. We postulated that aldosterone blockade with spironolactone might also have beneficial effects on the prognostic markers of endothelial function and heart rate variability in diabetic patients. Methods We assessed endothelial function by forearm venous occlusion plethysmography in 42 patients with Type 2 diabetes mellitus after 1 month of treatment with spironolactone or placebo allocated in a randomised double-blind trial. Of the 42 patients, 20 were on ACE inhibitor therapy. We also assessed heart rate variability, HbA1c and plasma angiotensin II levels at the end of each treatment period. Results Compared to placebo, spironolactone decreased forearm blood flow response to acetylcholine by 44.56±14.56% (p=0.003) in the group as a whole and by 57.61±15.56% (p<0.001) in the 20 patients on ACE inhibition. Spironolactone also worsened heart rate variability parameters, with root mean squared standard deviation decreased by 1.99±0.93 ms (p=0.03), low-frequency normalised power increased by 2.00±0.91 normalised units (nu) (p=0.03), high-frequency normalised power decreased by 1.98±0.94 nu (p=0.04) and the low frequency : high frequency ratio increased by 0.40±0.19 (p=0.04). HbA1c and angiotensin II increased during treatment with spironolactone by 0.26±0.07% (p=0.001) and 8.12±1.94 pg/ml (p=0.001) respectively. Conclusions/interpretation Spironolactone worsened endothelial function and heart rate variability in patients with Type 2 diabetes. These findings are possibly due to the worsening of glycaemic control and increase in plasma angiotensin II that were seen with spironolactone treatment. Thus the prescription of spironolactone to diabetic patients without heart failure does not seem to be justified.
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Keywords {🔍}

spironolactone, patients, heart, endothelial, function, rate, google, scholar, ace, pubmed, diabetes, variability, diabetic, aldosterone, treatment, inhibition, study, article, subjects, angiotensin, placebo, arm, cas, type, failure, blockade, blood, control, significant, cardiovascular, dysfunction, table, effects, hbac, group, increase, infusion, fbf, analysed, circulation, flow, acetylcholine, response, risk, effect, results, worsening, vascular, struthers, mellitus,

Topics {✒️}

perindopril-based blood-pressure-lowering regimen ml·min−1·100 ml−1 forearm volume angiotensin-converting enzyme inhibition adverse long-term outcome renin-angiotensin-system blockade randomised double-blind trial intensive blood-glucose control short-term variability low-frequency elements normalised long-term cardiovascular events insulin-dependent diabetes mellitus insulin-dependent diabetes mellitus privacy choices/manage cookies forearm blood flow multiple metabolic syndrome double-blind trial reflect parasympathetic status chronic quinapril administration chronic heart failure reflect sympathovagal imbalance renin-angiotensin system heart rate variability diastolic blood pressure impaired endothelium-dependent medical research ethics uric acid increased constant rate infuser long-term follow high-frequency power mild heart failure improve endothelial function strain gauge plethysmography high-frequency elements coronary heart disease frequency domain tracings low-frequency power adverse effect profile longer term measures endothelial function testing impaired endothelial function improved endothelial function british heart foundation angiotensin ii increased increased angiotensin ii peripheral vascular disease suppresses vascular angiotensin age/rage axis oral hypoglycaemic tablets temperature-controlled room 27-gauge needle mounted

Questions {❓}

Is there a potential association between spironolactone and the risk of new-onset diabetes in a cohort of older patients with heart failure?
Struthers AD (1999) Why does spironolactone improve mortality over and above an ACE inhibitor in chronic heart failure?
Vita JA, Keaney JF Jr (2002) Endothelial function: a barometer for cardiovascular risk?

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         headline:Spironolactone impairs endothelial function and heart rate variability in patients with Type 2 diabetes
         description:Aldosterone blockade has followed in the footsteps of ACE inhibition in reducing mortality in patients with heart failure. This is associated with its beneficial effects on endothelial function and heart rate variability. Diabetes is another area, where angiotensin II withdrawal has proven to be of particular value. We postulated that aldosterone blockade with spironolactone might also have beneficial effects on the prognostic markers of endothelial function and heart rate variability in diabetic patients. We assessed endothelial function by forearm venous occlusion plethysmography in 42 patients with Type 2 diabetes mellitus after 1 month of treatment with spironolactone or placebo allocated in a randomised double-blind trial. Of the 42 patients, 20 were on ACE inhibitor therapy. We also assessed heart rate variability, HbA1c and plasma angiotensin II levels at the end of each treatment period. Compared to placebo, spironolactone decreased forearm blood flow response to acetylcholine by 44.56±14.56% (p=0.003) in the group as a whole and by 57.61±15.56% (p<0.001) in the 20 patients on ACE inhibition. Spironolactone also worsened heart rate variability parameters, with root mean squared standard deviation decreased by 1.99±0.93 ms (p=0.03), low-frequency normalised power increased by 2.00±0.91 normalised units (nu) (p=0.03), high-frequency normalised power decreased by 1.98±0.94 nu (p=0.04) and the low frequency : high frequency ratio increased by 0.40±0.19 (p=0.04). HbA1c and angiotensin II increased during treatment with spironolactone by 0.26±0.07% (p=0.001) and 8.12±1.94 pg/ml (p=0.001) respectively. Spironolactone worsened endothelial function and heart rate variability in patients with Type 2 diabetes. These findings are possibly due to the worsening of glycaemic control and increase in plasma angiotensin II that were seen with spironolactone treatment. Thus the prescription of spironolactone to diabetic patients without heart failure does not seem to be justified.
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      headline:Spironolactone impairs endothelial function and heart rate variability in patients with Type 2 diabetes
      description:Aldosterone blockade has followed in the footsteps of ACE inhibition in reducing mortality in patients with heart failure. This is associated with its beneficial effects on endothelial function and heart rate variability. Diabetes is another area, where angiotensin II withdrawal has proven to be of particular value. We postulated that aldosterone blockade with spironolactone might also have beneficial effects on the prognostic markers of endothelial function and heart rate variability in diabetic patients. We assessed endothelial function by forearm venous occlusion plethysmography in 42 patients with Type 2 diabetes mellitus after 1 month of treatment with spironolactone or placebo allocated in a randomised double-blind trial. Of the 42 patients, 20 were on ACE inhibitor therapy. We also assessed heart rate variability, HbA1c and plasma angiotensin II levels at the end of each treatment period. Compared to placebo, spironolactone decreased forearm blood flow response to acetylcholine by 44.56±14.56% (p=0.003) in the group as a whole and by 57.61±15.56% (p<0.001) in the 20 patients on ACE inhibition. Spironolactone also worsened heart rate variability parameters, with root mean squared standard deviation decreased by 1.99±0.93 ms (p=0.03), low-frequency normalised power increased by 2.00±0.91 normalised units (nu) (p=0.03), high-frequency normalised power decreased by 1.98±0.94 nu (p=0.04) and the low frequency : high frequency ratio increased by 0.40±0.19 (p=0.04). HbA1c and angiotensin II increased during treatment with spironolactone by 0.26±0.07% (p=0.001) and 8.12±1.94 pg/ml (p=0.001) respectively. Spironolactone worsened endothelial function and heart rate variability in patients with Type 2 diabetes. These findings are possibly due to the worsening of glycaemic control and increase in plasma angiotensin II that were seen with spironolactone treatment. Thus the prescription of spironolactone to diabetic patients without heart failure does not seem to be justified.
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