Rationale:

The nocturnal blood pressure mean is an independent and stronger predictor of cardiovascular disease (CVD) risk than either daytime office, awake or 24hour mean blood pressure. In general, when nocturnal blood pressure does not decline CVD risk is higher, usually referred to as "dippers" versus "non-dippers". Evening administration of treatment might lower nocturnal blood pressure more effectively than morning administration, which is most commonly advised.

The main hypothesis of this study is that evening administration of antihypertensive medication might resume the dipping pattern in non-dippers and as a consequence might reduce CVD risk more than morning administration.

Primary objective (in short):

-to prove that evening administration of enalapril/hydrochlorothiazide in non-dippers can resume a dipping blood pressure pattern in non-dippers

Study design: A double-blind placebo-controlled cross-over study Each person will use for one period of six weeks enalapril/hydrochlorothiazide in the morning and placebo in the evening, and one period of six weeks the other way around

Inclusion Criteria:

• Essential hypertension
• Stable blood pressure on treatment with Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Blocker (ARB) and hydrochlorothiazide
• Age between 18 and 85 years
• WHO performance status 0-1
• Available for a time period of 15 weeks
• Written informed consent
• Dippers: Nocturnal blood pressure fall of 10-20% of daytime values.20
• Non-dippers: -Nocturnal blood pressure fall of <10% of daytime values

Exclusion Criteria:

• secondary cause of hypertension
• use of ARB because of intolerability (e.g. dry cough) of ACEI
• nocturnal blood pressure fall of >20% or rise
• renal insufficiency (GFR<60 ml/min)
• shift work
• pregnancy or wish to get pregnant
• use of other antihypertensive medication than ACEI, ARB, hydrochlorothiazide or a calcium channel blocker
• use of sleeping medication