Effect of rosuvastatin on cardiac remodeling, function, and progression to heart failure in hypertensive heart with established left ventricular hypertrophy.
Hypertensive patients with left ventricular hypertrophy (LVH) are the most common high-risk group to develop heart failure with preserved ejection fraction. Recent reports have noted the favorable effect of statins on LVH. We evaluated the effect of rosuvastatin on cardiac remodeling, function, and progression to heart failure in a hypertensive rat model with established LVH. Dahl salt-sensitive rats were fed a high-salt diet until 13 weeks of age. After LVH was confirmed by echocardiography, rats were randomly assigned to control and statin treatment (n=18 each group). The statin-treated group was treated with rosuvastatin until 21 weeks of ages. Serial echocardiography, blood pressure monitoring, and miniaturized conductance catheter hemodynamic monitoring were performed at 21 weeks. Echocardiographic parameters were not significantly different between the groups. On hemodynamic monitoring, systolic performance parameters were similar between the groups, whereas end diastolic pressure-volume relationships were lower in the statin-treated group (0.014+/-0.008 versus 0.008+/-0.004 mm Hg/muL, P<0.05), suggesting improvement in myocardial stiffness. Pathological analysis showed attenuation of perivascular and interstitial fibrosis in the statin-treated group (P<0.02). Rosuvastatin therapy did not alleviate LVH in hypertensive rats with established LVH, but it attenuated myocardial fibrosis and LV stiffness. It seems that rosuvastatin has limited therapeutic value when used to prevent progression from LVH to heart failure in hypertensive hearts.
Chang
Sung-A
SA
Associate Professor, Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea. kimdamas@snu.ac.kr.
Kim
Yong-Jin
YJ
Lee
Hye-Won
HW
Kim
Dae-Hee
DH
Kim
Hyung-Kwan
HK
Chang
Hyuk-Jae
HJ
Sohn
Dae-Won
DW
Oh
Byung-Hee
BH
Park
Young-Bae
YB
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D005355:Fibrosis / Q000517:prevention & control; D005464:Fluorobenzenes / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D020303:Rats, Inbred Dahl; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D003094:Collagen