Effect of quinapril, quinapril-hydrochlorothiazide, and enalapril on the bone mass of hypertensive subjects: relationship with angiotensin converting enzyme polymorphisms.
BACKGROUND
Many alterations in extracellular metabolism of calcium have been associated to hypertension, but the number of studies relating this disease with osteoporosis is extremely low. This study clarifies the therapeutic effect of three treatments-quinapril, quinapril + hydrochlorothiazide (HCTZ), enalapril-on bone remodeling markers, bone mineral density (BMD) in hypertensive patients, and relationship with angiotensin converting enzyme (ACE) polymorphism.


METHODS
This open, prospective study included 134 patients with low-to-moderate hypertension and stable BMD according to Joint National Committee criteria and 96 patients completed the study. After a washout period, patients were randomized to one of the three treatments, which they received for 1 year. Analyses of blood and urine samples and densitometric studies on lumbar spine were performed.


RESULTS
Calcium and 25-hydroxyvitamin D levels increased (9.5 +/-0.3 and 9.6 +/-0.3 mg/dL, P =.01 and 46 +/-22 and 58 +/-22 nmol/L, P =.026, respectively) in the quinapril-treated group and calcium levels increased (9.4 +/-0.6 and 9.8 +/-0.4 mg/dL, P =.001) in the quinapril-HCTZ-treated group. The 1, 25-dihydroxyvitamin D levels, calciuria, and calcium/creatinine ratio decreased (64 +/-23 and 43 +/-16 nmol/L, P =.0001;209 +/-93 and 161 +/-93 mg/24 h, P =.0022;0.21 +/-0.09 and 0.17 +/-0.11, P =.04, respectively). In the enalapril-treated group 1, 25-dihydroxyvitamin D levels (61 +/-27 and 42 +/-19 nmol/L, P =.0022) decreased. Only women presented a statistical significance (1.064 +/-0.16 g/cm(2), P =.034) between ID+II polymorphism and BMD decrease, and between DD polymorphism with less BMD under baseline conditions and a BMD increase (1.070 +/-0.16 g/cm(2), P =.017) after ACE inhibitor treatment.


CONCLUSIONS
The ACE inhibitors have a beneficial effect on BMD and calcium metabolism alterations in hypertensive subjects. Concerning BMD response, women presenting with the II+ID polymorphism had a poor response to antihypertensive drug treatment, whereas women with the DD polymorphism responded better. This is the first study demonstrating a relationship between ACE polymorphism and BMD response and antihypertensive ACE inhibitor treatment.
Pérez-Castrillón
José L
JL
Departamento de Medicina Interna, Hospital Universitario Río Hortega, Facultad de Medicina de Valladolid, Valladolid, Spain. castrv@terra.es
Silva
Jesús
J
Justo
Isabel
I
Sanz
Alberto
A
Martín-Luquero
Miguel
M
Igea
Rosa
R
Escudero
Pilar
P
Pueyo
Carol
C
Díaz
Cristina
C
Hernández
Gonzalo
G
Dueñas
Antonio
A
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D006706:Homeostasis; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010758:Phosphorus / Q000378:metabolism; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D000077583:Quinapril; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D015415:Biomarkers; D044005:Tetrahydroisoquinolines; D006852:Hydrochlorothiazide; D010758:Phosphorus; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D000077583:Quinapril; D002118:Calcium