Impact of an ACE inhibitor and calcium antagonist on microalbuminuria and lipid subfractions in type 2 diabetes: a randomised, multi-centre pilot study.
BACKGROUND
Microalbuminuria (MA) is associated with increased cardiovascular risk and lipid abnormalities in people with type 2 diabetes. ACE inhibitors and calcium channel blockers (CCBs) reduce MA and are neutral on total cholesterol and triglycerides. The effect of ACE inhibitors and CCBs on lipid subfractions such as Lp(a), apolipoprotein (apo) A1, apo B, and others, however, is unclear. The current study tests the hypothesis that a fixed-dose combination of an ACE inhibitor, benazepril (B) with the dihydropyridine CCB, amlodipine (A), will further reduce arterial pressure and reduce atherogenic lipid fractions compared to either agent alone.


METHODS
A multicentre, randomised, open-label, parallel group design was used to study 27 participants with type 2 diabetes. Measurements for total cholesterol, high- and low-density lipoprotein (HDL and LDL), triglycerides, apo A1, apo B, Lp(a), MA, arterial pressure and creatinine clearance were obtained at baseline and at 12-week intervals during the 36 week study.


RESULTS
Arterial pressure was significantly reduced at 36 weeks in all three groups (P = 0.0078 for A, P = 0.0039 for B, and P = 0.0313 for A+B). MA was lowered in all groups with relatively greater reductions in the B (P < 0.05) and A+B groups (P < 0.03) vs A. An increase in mean HDL-cholesterol from baseline was noted in the B and A+B groups; P < 0.05), but not in the A group. A trend was also observed between the rise in HDL-cholesterol and the reduction in MA in the B and A+B groups. Additionally, only the B group exhibited a decrease in the median value of Lp(a) (P < 0.05).


CONCLUSIONS
These data support the concept that ACE inhibition with B reduces the atherogenic profile by decreasing Lp(a) and increasing HDL-cholesterol, the latter being correlated with reductions in MA. While A+B exhibited similar trends in lipid subfractions and MA as B, this group had the greatest reduction in systolic blood pressure of the three groups. Thus, use of A+B offers the benefits of a decreased atherogenic profile with a higher probably of achieving goal blood pressure as recommended by national guidelines.
Bakris
G L
GL
Department of Preventive Medicine, Rush Hypertension/Clinical Research Center, Chicago, IL 60612, USA.
Smith
A C
AC
Richardson
D J
DJ
Hung
E
E
Preston
R
R
Goldberg
R
R
Epstein
M
M
D000368:Aged; D000419:Albuminuria / Q000378:metabolism*; D017311:Amlodipine / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001053:Apolipoproteins / Q000097:blood; D053241:Apoprotein(a); D001552:Benzazepines / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004095:Dihydropyridines / Q000627:therapeutic use; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014280:Triglycerides / Q000097:blood*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001053:Apolipoproteins; D001552:Benzazepines; D002121:Calcium Channel Blockers; D008076:Cholesterol, HDL; D004095:Dihydropyridines; D017270:Lipoprotein(a); D014280:Triglycerides; D017311:Amlodipine; C038806:1,4-dihydropyridine; D002784:Cholesterol; D053241:Apoprotein(a); C044946:benazepril