Simvastatin and Diastolic Dysfunction

Study Overview
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Brief Summary
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Diastolic dysfunction (DD) is an increasingly frequent condition in hypertensive individuals whose treatment remains unclear. Its presence is related to higher morbidity and mortality independent of blood pressure levels. The aim of this study is to investigate the additive effect of simvastatin on enalapril on DD in hypertensive patients with average cholesterol levels. For this aim, hypertensive patients with DD and LDL-cholesterol <160 mg/dL will undergo a run-in phase to achieve a systolic blood pressure (SBP) <135 mmHg and diastolic blood pressure (DBP) <85 mmHg with enalapril. Hydrochlorothiazide could be added when need to achieve SBP or DBP control. Four weeks after reaching the optimum anti-hypertensive regimen patients will be randomized to receive 80 mg simvastatin or placebo for a period of 20 weeks. Echocardiograms will be performed before and after treatment with measurement of left atrial volume, conventional and tissue Doppler velocities in early diastole and late diastole. The evaluation of these will allow to identify changes of DD severity after treatment.

Official Title
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Effect of the Addition of Simvastatin to Enalapril in Hypertensive Individuals With Average Cholesterol Levels and Diastolic Dysfunction

Conditions
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Diastolic Dysfunction, Hypertension

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men or postmenopausal women aged between 40 and 65 years old normal fasting blood glucose (<100 mg/dL) and glucose tolerance test (<140 mg/dL) waist circumference < 102 cm (men) or < 88cm (women) triglycerides <150 mg/dL, LDL cholesterol ≤ 160 mg/dl creatinine <1.2 mg/dL, sinus rhythm the presence of grade 1 or 2 of DD with an ejection fraction of left ventricle > 55% absence of myocardial ischemia during dobutamine stress echocardiography Exclusion Criteria: thyroid dysfunction acute or chronic liver disease regular use of 3 or more antihypertensive drugs secondary hypertension symptoms or history of atherosclerotic disease valvular dysfunction LVH 14 and use of statins in the last 6 months

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* 1 pill once a day<br>|
| Experimental: Simvastatin<br>Simvastatin 80 mg/day | Drug: Simvastatin<br>* 80 mg once a day<br>* Other names: Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in E/A ratio and e' wave velocity |  | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in left atrium volume. |  | 20 weeks | 
| Changes in left ventricular mass. |  | 20 weeks | 
| Changes in e´/a´ waves ratio. |  | 20 weeks | 
| Changes in mitral deceleration time. |  | 20 weeks | 
| Changes in the ratio of mitral inflow velocity to annular relaxation velocity. |  | 20 weeks | 
| Changes in mitral annulus systolic velocity |  | 20 weeks | 
| Diastolic function reserve index measured at peak stress with dobutamine |  | 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diastolic dysfunction, hypertension, Statins, ACE inhibitor, Echocardiography