Cardiovascular Response to Exercise in Hypertension
Condition: Hypertension
MeSH terms: Hypertension
Study type: Observational

Summary: 
      Arterial hypertension (AH) is an important clinical social and economic problem, related to
      the increased cardiovascular risk. AH is associated with cardiovascular hemodynamic
      alterations, including left ventricular diastolic dysfunction (LVddf). In consequence of
      increased blood pressure, the effectiveness of LV as a blood pump decreases and the symptoms
      of heart failure (HF) may occur. Thus, the identification of noninvasive markers related with
      the progression from the asymptomatic AH to LVddf/HFpEF would be beneficial.

      Another issue is that the diagnostic difficulties in patients with LVddf and HFpEF stem from
      the limited possibility to assess the hemodynamic response to exercise. Thus, there is a need
      for more detailed methods of cardiovascular monitoring while exercise testing.

      We hypothesize that some new noninvasive hemodynamic parameters, characterizing left
      ventricular (LV) function and arterial stiffness, may help to predict the risk of
      cardiovascular events and future occurrence of LVddf/HFpEF. Moreover, we assume that
      cardiopulmonary exercise test (CPET), completed with new methods of noninvasive hemodynamic
      monitoring (impedance cardiography and applanation tonometry), would provide additional value
      in the assessment of the cardiovascular hemodynamic response to exercise.

      The study is intended to verify these hypothesis.
    

Detailed description: 
      Arterial hypertension (AH) is an important clinical social and economic problem, related to
      the increased cardiovascular risk.

      AH is associated with cardiovascular hemodynamic alterations, including left ventricular
      diastolic dysfunction (LVddf). In consequence of increased blood pressure, the effectiveness
      of LV as a blood pump decreases and the symptoms of heart failure (HF), even with preserved
      ejection fraction (HFpEF), may occur. At the early stage, patients' complaints are not
      specific and difficult to clinical interpretation. As a consequence, these subjects
      frequently remain undiagnosed. Thus, the identification of noninvasive markers related with
      the progression from the asymptomatic AH to LVddf/HFpEF would be beneficial.

      Another issue is that the diagnostic difficulties in patients with LVddf and HFpEF stem from
      the limited possibility to assess the hemodynamic response to exercise. Thus, there is a need
      for more detailed methods of cardiovascular monitoring while exercise testing.

      The investigators hypothesize that some new noninvasive hemodynamic parameters,
      characterizing left ventricular (LV) function and arterial stiffness, may help to predict the
      risk of cardiovascular events and future occurrence of LVddf/HFpEF. Moreover, the
      investigators assume that cardiopulmonary exercise test (CPET), completed with new methods of
      noninvasive hemodynamic monitoring (impedance cardiography and applanation tonometry), would
      provide additional value in the assessment of the cardiovascular hemodynamic response to
      exercise.

      Aims:

        1. The identification of the new markers of cardiovascular risk in patients with arterial
           hypertension..

        2. The identification of the new markers of progression from normal left ventricular
           diastolic function to left ventricular diastolic dysfunction.

        3. The identification of the new noninvasive markers of progression to symptomatic heart
           failure.

        4. The evaluation of the feasibility and usefulness of new methods of noninvasive
           hemodynamic monitoring (impedance cardiography and applanation tonometry) in the
           assessment of the cardiovascular hemodynamic response to exercise.

        5. Multivariate assessment of cardiovascular response to the controlled exercise, taking
           into account left ventricular diastolic function and symptoms of heart failure.

        6. The relation between laboratory markers of left ventricular remodeling with resting and
           exercise (noninvasive) hemodynamics.

      The study will be performed in a prospective and observational design. No less than 120
      hypertensive subjects will be enrolled.

      After recruitment the following assessment will be performed:

        -  anamnesis and physical examination with anthropometrics (including body composition
           analysis with use of bioimpedance method);

        -  electrocardiogram;

        -  echocardiography (resting), including assessment of left ventricular systolic (2-D left
           ventricular ejection fraction, longitudinal strain) and diastolic function (including
           tissue Doppler imaging);

        -  impedance cardiography (resting);

        -  Applanation tonometry (resting);

        -  24-h Holter-ekg (including heart rate variability analysis);

        -  24-h ambulatory blood pressure monitoring;

        -  flow-mediated dilation of brachial artery (FMD);

        -  6-minute walking test (6-MWT);

        -  Cardiopulmonary exercise test (CPET), supported by hemodynamic monitoring with impedance
           cardiography and applanation tonometry;

        -  Quality of life assessment (SF 36 questionnaire);

        -  Laboratory tests (including creatinine, urea, uric acid, lipids, glucose,
           microalbuminuria, N-terminal of the prohormone brain natriuretic peptide, galectin-3,
           copeptin, soluble ST2, Growth differentiation factor 15 (GDF-15), human tissue inhibitor
           of metalloproteinases 1 (TIMP-1), metalloproteinase 2 (MMP-2), metalloproteinase 9
           (MMP-9), syndecan-1).

      After 12 months (first control visit) and 24 months (second control visit) the
      echocardiography and clinical assessment (HF symptoms) will be performed to identify: 1/
      patients with new onset LVDdf (among group N); 2/ patients with new onset HF (among group D)

      Morover, the follow-up of min 48 months concerning cardiovascular events will be performed
      (as defined below)
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        No less than 120 hypertensive subjects (both sexes, aged 40-75 years) will be enrolled,
        including those with: 1/ no symptoms of HF and normal LV diastolic function (group N, no
        less than 40 subjects), 2/ no symptoms of HF and LVddf (group D, no less than 40 subjects),
        3/ with symptoms of both HF and LVddf (group D_HF, no less than 40 subjects).
      
Keywords: hypertension; exercise; diastolic heart failure