Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between Azelnidipine and amlodipine on glucose tolerance and endothelial function - a crossover trial (AGENT)

<p>Abstract</p> <p>Background</p> <p>Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice.</p> <p>Methods</p> <p>Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT.</p> <p>Results</p> <p>Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (<it>P </it>< 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both <it>P </it>< 0.05). Serum levels of high-sensitivity C-reactive protein (<it>P </it>= 0.067) and interleukin-6 (<it>P </it>= 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (<it>P </it>= 0.016).</p> <p>Conclusions</p> <p>These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension.</p

The transluminal attenuation gradient in coronary CT angiography for the detection of hemodynamically significant disease: can all arteries be treated equally?

OBJECTIVE:Results of the use of the transluminal attenuation gradient (TAG) at coronary CT angiography (CCTA) to predict hemodynamically significant disease vary widely. This study tested whether diagnostic performance of TAG to predict fractional flow reserve (FFR) ≤&nbsp;0.8 is improved when applied separately to subsets of coronary arteries that carry similar physiological flow. METHODS:28 patients with 64&nbsp;×&nbsp;0.5 mm CCTA and invasive FFR in ≥1 major coronary artery were retrospectively evaluated. Two readers assessed TAG in each artery. The receiver operating characteristic (ROC)&nbsp;area under the curve (AUC) was used to assess the diagnostic performance of TAG to detect hemodynamically significant disease following a clinical use rule [negative: FFR&nbsp;&gt;&nbsp;0.8 or ≤&nbsp;25% diameter stenosis (DS) at invasive catheter angiography; positive: FFR&nbsp;≤&nbsp;0.8 or ≥&nbsp;90% DS at invasive catheter angiography]. ROC AUC was compared for all arteries pooled together, vs separately for arteries carrying similar physiological flow (Group 1: all left anterior descending plus right-dominant left circumflex; Group 2: right-dominant RCA plus left/co-dominant left circumflex). RESULTS:Of the 84 arteries, 30 had FFR measurements, 30 had ≤25% DS and 13 had ≥90% DS. 11 arteries with 26-89% DS and no FFR measurement were excluded. TAG interobserver reproducibility was excellent (Pearson r&nbsp;=&nbsp;0.954, Bland-Altman bias: 0.224 Hounsfield unit&nbsp;cm-1). ROC AUC to detect hemodynamically significant disease was higher when considering arteries separately (Group 1 AUC&nbsp;=&nbsp;0.841, p&nbsp;=&nbsp;0.039; Group 2 AUC&nbsp;=&nbsp;0.840, p&nbsp;=&nbsp;0.188), than when pooling all arteries together (AUC&nbsp;=&nbsp;0.661). CONCLUSION:Incorporating information on the physiology of coronary flow via the particular vessel interrogated and coronary dominance may improve the accuracy of TAG, a simple measurement that can be quickly performed at the time of CCTA interpretation to detect hemodynamically significant stenosis in individual coronary arteries. Advances in knowledge: The interpretation of TAG may benefit by incorporating information regarding which coronary artery is being interrogated

The transluminal attenuation gradient in coronary CT angiography

OBJECTIVE: Results of the use of the transluminal attenuation gradient (TAG) at coronary CT angiography (CCTA) to predict hemodynamically significant disease vary widely. This study tested whether diagnostic performance of TAG to predict fractional flow reserve (FFR) ≤ 0.8 is improved when applied separately to subsets of coronary arteries that carry similar physiological flow. METHODS: 28 patients with 64 × 0.5 mm CCTA and invasive FFR in ≥1 major coronary artery were retrospectively evaluated. Two readers assessed TAG in each artery. The receiver operating characteristic (ROC) area under the curve (AUC) was used to assess the diagnostic performance of TAG to detect hemodynamically significant disease following a clinical use rule [negative: FFR > 0.8 or ≤ 25% diameter stenosis (DS) at invasive catheter angiography; positive: FFR ≤ 0.8 or ≥ 90% DS at invasive catheter angiography]. ROC AUC was compared for all arteries pooled together, vs separately for arteries carrying similar physiological flow (Group 1: all left anterior descending plus right-dominant left circumflex; Group 2: right-dominant RCA plus left/co-dominant left circumflex). RESULTS: Of the 84 arteries, 30 had FFR measurements, 30 had ≤25% DS and 13 had ≥90% DS. 11 arteries with 26-89% DS and no FFR measurement were excluded. TAG interobserver reproducibility was excellent (Pearson r = 0.954, Bland-Altman bias: 0.224 Hounsfield unit cm). ROC AUC to detect hemodynamically significant disease was higher when considering arteries separately (Group 1 AUC = 0.841, p = 0.039; Group 2 AUC = 0.840, p = 0.188), than when pooling all arteries together (AUC = 0.661). CONCLUSION: Incorporating information on the physiology of coronary flow via the particular vessel interrogated and coronary dominance may improve the accuracy of TAG, a simple measurement that can be quickly performed at the time of CCTA interpretation to detect hemodynamically significant stenosis in individual coronary arteries. Advances in knowledge: The interpretation of TAG may benefit by incorporating information regarding which coronary artery is being interrogated