Predisposition and Transition Mechanisms From Arterial Hypertension to Heart Failure

Genetics and Genomics of Hypertension Associated With Microinflammation, Oxydative Stress, Chronic Renal Disease and Heart Failure (A2-B2-B3)

This project aims at investigating the genetic, genomic and proteomic basis of hypertension and susceptibility to hypertension-related end organ damage (renal damage and heart failure). It will include cross sectional as well as follow-up studies with a large number of subjects and variety of phenotypes, to explore the pathophysiology of hypertension and hypertension-related disease.

In all index patients and recruited family members, recorded data will include the following :

• Past medical history, drug history and family history
• Physical examination
• Height, weight, waist and hip circumference
• Cardiac examination
• Vascular examination
• Blood pressure
• Plasma and urine samples
• Body composition (DEXA)
• Tissue Doppler imaging

Inclusion Criteria:

• index patient :

  • Caucasian patients of either sex who were diagnosed to have essential hypertension (as defined below) before the age of 50 y.

  • The index patient should not be older than 60 years at the time of enrolment.

  • Definition of hypertension for the index patient:

    • If untreated: Systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg.
    • If already on treatment: Treatment with more of 2 different antihypertensive drugs at the time of enrolment.

  • At least three first degree relatives of whom at least one should be affected and at least one be from a different generation (parents or offspring aged 18 years or above) must be willing to participate in the family study. For definition of hypertension in relatives of the index patient see below.

  • Written informed consent

• family

  • at least three other first degree relatives must be willing to participate in the family study:
  • at least one first-degree relative must be affected with diagnosis of hypertension made before age of 50 years AND
  • at least one first degree relative must be from a different generation (offspring or parents).

Exclusion Criteria:

• index patient :

  • Any known form of secondary hypertension, including sleep apnoea syndrome
  • Any known previous clinical complications of hypertension (angina, MI, stroke, TIA, peripheral artery disease) at any time
  • Any known renal disease, including GFR < 60 mL/min as estimated by the abbreviated MDRD formula, or kidney stones
  • Kidney or other organ transplantation
  • Type 1 diabetes mellitus
  • Heart failure stage D (AHA/ACC criteria)
  • Any malignant concomitant diseases or history of malignant diseases within the last five years, with exception of treated squamous skin cancer or basalioma
  • Clinical or laboratory signs of acute infection, especially urinary tract infection
  • Systemic inflammatory diseases, such as autoimmune diseases, connective tissue diseases or collagenoses.
  • Steroids or any other immunosuppressive drug
  • Severe known liver disease (ALT or gamma-GT above three-fold of upper normal limit)
  • Current alcohol consume of more than 21 drinks/week (1 drink = a bottle (0,33 l) beer, a glass (0,2 l) of wine, or 4 cl = 40 ml of spirit (40%)) or drug abuse such as cocaine

• family

  • any organ transplantation
  • any malignant concomitant disease
  • acute infection
  • systemic inflammatory disease
  • severe liver disease
  • current alcohol or drug abuse