Resistant Hypertension in Patients With Type-II-Diabetes Mellitus
Condition: Resistant Hypertension; NIDDM
MeSH terms: Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Observational

Summary: 
      The risk of cardiovascular disease (CVD) in patients with type-II-diabetes mellitus
      (type-II-DM)is more than doubled and CVD accounts for 70% of deaths in this group of
      patients.

      Hypertension is a major risk factor for CVD in patients with type-II-DM and a major
      contributor cardiovascular mortality. Uncontrolled- (UH) and resistant hypertension (RH)are
      more common in patients with type-II-DM, why further bloodpressure (BP) control is needed.

      The prevalence of UH and RH has not been examined in a consecutive Danish outpatient
      population with type-II-DM.

      The purpose of this study is to examine the prevalence of resistant hypertension in patients
      with type-II-diabetes and to examine the characteristics of patients with resistant
      hypertension as compared to patients with controlled hypertension with regards to arterial
      stiffness.
    

Detailed description: 
      The risk of cardiovascular disease (CVD) in patients with type-II- diabetes mellitus
      (type-II-DM) is more than doubled and CVD accounts for 70% of deaths in this group of
      patients. Hypertension is a major risk factor for CVD in patients with type-II-DM with a
      major increase in diabetes-related death as a result. Controlled hypertension as well as
      uncontrolled- and resistant hypertension is more common in patients with type-II-DM than in
      the general population and are major contributors to CVD and cardiovascular mortality.

      Resistant hypertension is defined as BP above 130 mmHg systolic and / or 80 mmHg diastolic
      despite treatment with 3 antihypertensive agents or more, of which one should be a diuretic,
      or controlled BP on four antihypertensive agents or more.

      The NHANES study estimated the prevalence of hypertension in patients with type-II-DM to 71%
      and showed that among those with type-II-DM and hypertension only 31% had controlled BP. It
      is furthermore estimated that resistant that hypertension is present in up to 30% of a
      hypertensive population and the ALLHAT trial found that 50% of hypertensives needed treatment
      with three or more antihypertensive agents.

      Type-II-DM promotes both small and large artery disease, whereas hypertension promotes
      primarily large artery disease. As such type-II-DM and hypertension together may influence
      the entire vascular system. Type-II-DM is strongly associated with development of heart
      failure and atherosclerosis and it is therefore important to investigate parameters that
      reflect arterial stiffness (AS), left ventricular function and degree of atherosclerosis.

      AS is an age dependent process, where the arterial wall degenerate and elastic fibers are
      replaced by collagen fibers. The process is accelerated by cardiac risk factors and increased
      AS can be regarded as both an individual risk factor and a marker reflecting atherosclerosis.

      AS can be estimated by pulse wave analysis (PWA) including pulse wave velocity (PWV).

      As blood is pumped out of the heart, a pulse wave is created. The pulse wave propagates along
      the vessels and is reflected from the arterial wall at sites of increased impedance. In
      healthy elastic arteries the reflected wave reaches the aorta during diastole resulting in
      increased coronary perfusion. In stiff arteries the reflected wave propagates faster and
      reaches the aorta during systole before closure of the aortic valve, thereby increasing pulse
      pressure, systolic pressure and reducing diastolic pressure and thereby coronary perfusion.

      Augmentation Index (AIx) measured using PWA is related to ischemic heart disease (IHD) risk
      factors, among other hypertension and diabetes, and is an independent predictor of mortality
      in patients with IHD. It is therefore important to examine the relationship between BP and
      AS, as it may characterize the patients with uncontrolled and resistant hypertension.

      A consequence of increased AS is left ventricular hypertrophy (LVH) and a common
      echocardiographic finding in patients with hypertension, type-II-DM and LVH, is diastolic
      dysfunction. This is often seen before the onset of systolic dysfunction and any symptoms of
      CVD.

      Coronary artery calcium (CAC) score is closely related to atherosclerosis and is a number
      reflecting the degree and extent of calcium deposits in the walls of the coronary arteries,
      as demonstrated by cardiac computed tomography. CAC score represents overall plaque burden
      and is also an independent predictor of cardiovascular events (CVE) and cardiovascular death
      in asymptomatic patients. In patients with type-II-DM the extent of CAC score is similar to
      that of patients with coronary artery disease (CAD). Measurement of CAC score can be used as
      advanced risk assessment. As CAC score is high in patients with cardiac risk factors it is
      possible that CAC score is reduced when minimizing cardiac risk factors.

      The relationship between BP, AS and left ventricular function score may provide further
      methods of risk stratification and new strategies for treatment of uncontrolled and resistant
      hypertension in patients with type-II-DM.

      Hypothesis

        1. Uncontrolled and resistant hypertension is present in more than 50% of consecutive
           patients with type-II-DM in an out-patient clinic.

        2. Increased AS, diastolic dysfunction and high CAC score are more common in patients with
           type-II-DM with uncontrolled or resistant hypertension than in patients with controlled
           BP.

        3. AS, diastolic function and CAC are improved with increased control of BP.

      To test these hypotheses we wish to conduct two studies:

        1. A descriptive study in which the prevalence of uncontrolled and resistant hypertension
           in consecutive out-patients with type-II-DM is assessed.

        2. Assessment of AS, diastolic function and CAC in patients with type-II-DM with
           uncontrolled and resistant hypertension and the changes in these parameters during
           intensified treatment. This is compared to patients with controlled BP.
    

Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients from diabetic outpatient clinic
      
Biospecimen description: 
      Only serum and plasma samples are used and saved for later analysis.
    
Keywords: Resistant hypertension; Type-II-Diabetes Mellitus; Arterial stiffness; Ventricular function