Year-round Health Enhancing Exercise and Coronary Artery Disease
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Study type: Interventional

Summary: 
      A cold season involves higher cardiovascular morbidity and mortality. Several epidemiologic
      studies have implicated that persons with a cardiac disease, such as coronary artery disease
      (CAD) may be at higher risk for these adverse health events, but the mechanisms are not well
      established. Because both exercise and cold exposure stimulates cardiac and circulatory
      functions it is important to study their interaction especially among people with CAD and
      whose myocardial oxygen supply and function are weakened. The study examines how recommended
      health-enhancing upper and lower body exercise and warm-up in combination with cold exposure
      affects cardiovascular functions of people with CAD.

      The research includes randomized controlled experiments where the participants are 35-75 year
      old men with CAD (CCS I-II) and recruited from the Oulu University Hospital. Each participant
      undergoes four different trials in random order where the temperature (+22°C or -15°C) and
      the form of exercise (brisk walking at 5.5 km/h or upper body exercise at 30 W), and warm-up
      regime is varied. The used exercise, clothing and exposure resemble an ordinary wintertime
      exercise event. Novel techniques are used to broadly assess cardiovascular function before,
      during and in the recovery phase.

      The obtained information is synthesized and translated to tailored year-round exercise
      instructions for people with CAD by the research team including experts from sports sciences,
      physiology, public and occupational health, clinical sciences and with complementary
      knowledge in physical activity, effective interventions and cardiovascular function. The
      study has broad national and international impact on the relatively passive aging population
      having CAD and residing and working in a cold climate. The produced information enables
      finding means to activate persons with CAD and where appropriate and safe year-round exercise
      may reduce or prevent adverse health effects. Health care personnel will have an improved
      possibility to prescribe physical activity programs for their clients and enabling better
      instructions of healthy and safe exercise as a way to promote health.
    

Detailed description: 
      Introduction

      National and International significance of the research

      According to a worldwide estimate 42% of people with coronary artery disease (CAD) are
      physically inactive. There are approximately 200 000 persons in Finland with CAD, and even
      more have other connected health problems (high cholesterol or blood pressure, diabetes)
      further weakening their cardiac function and physical capacity and causing mortality. This
      increasing ageing population are often inactive, but would benefit substantially from regular
      year-round physical activity for maintaining their functional ability and independent living.

      At present it is not known whether the exercise recommendation for CAD patients involves a
      health risk during cold exposure as they regularly report symptoms of chest pain and
      arrhythmias in the winter. Because both exercise and cold exposure stimulates cardiac and
      circulatory functions precise physical activity require defining their interaction among CAD
      patients whose myocardial oxygen supply and function are weakened.

      Nationally and internationally the research addresses a large and special population group
      living in the northern hemisphere, whose symptoms, health events and mortality are common and
      provoked in the cold season. A passive lifestyle of this population is partially due to
      inadequate instructions and guidance. As a result of ageing the proportion of people with CAD
      will increase which emphasizes the role of prevention in reducing health care costs. The
      proposed research entity forms an important part of the research program examining the direct
      effect of temperature on human health in the newly established WHO Collaboration Centre in
      Global change, Environment and Public Health.

      Aims and hypotheses The aims are: 1) to study separate and combined effects of upper or lower
      body exercise and warm-up on cardiovascular response (acute, recovery) and to 2) translate
      the research information into tailored instructions for year-round physical activity.

      The hypotheses are: 1) moderate level endurance exercise increase cardiovascular strain in
      CAD patients in the cold compared to a warm environment, 2) upper body exercise is more
      strenuous than lower body exercise in the cold, 3) warm-up exercise attenuates the cold and
      exercise induced rise in BP

      Participants The participants are 35-75-year old men (non-smokers) with CAD (NYHA CCS I-II),
      have experienced a myocardial infarction over 3 months ago, have hypertension but no other
      metabolic, cardiovascular or respiratory disease. The participants are recruited from the
      Oulu University Hospital by an experienced cardiologist. The exclusion criteria are: smoking,
      asthma, CCS class III-IV, diabetes, previous myocardial infarction less than 3 months ago,
      chronic atrial fibrillation, claudication, unstable angina pectoris, serious complex
      arrhythmias or ECG anomalies during rest.

      Randomized controlled studies (n=160) The randomized controlled studies allow understanding
      causality and the physiological mechanisms for the separate and combined effects of exercise
      and cold on cardiovascular function in persons with CAD. Phase I (2015-16): Separate and
      combined effects of cold and exercise on cardiovascular function. Each participant (n=20) is
      randomly exposed to four conditions and separately to a neutral (+22°C) and cold (-15°C)
      environment during rest and exercise. Phase II (2016-17): Type of exercise and warm-up on
      cardiovascular function during exercise in the cold. Each participant (n=20) is randomly
      exposed to four conditions involving lower (brisk walking) or upper body (arm ergometry)
      exercise in the cold (-15°C) with or without warm-up exercise at +22°C. Each experimental
      session lasts for 105 min (15 min baseline + 30 min exposure + 60 min recovery).

      Ambient conditions The participants are exposed to both +22°C and -15°C (wind 1.4. m/s) for
      30 min per experimental session in the wind tunnel of the Kastelli Research Centre. The used
      cold exposure simulates conditions which occur frequently during the winter in a cold
      climate. The participants are equipped with winter clothing during the experiments. The cold
      exposure is largely restricted to the face which is known to increase BP by ca. 20 mmHg in
      healthy subjects.

      Study protocol

      The experimental sessions are performed at the same time of the day for each participant.
      Instructions to avoid heavy exercise or alcohol 48 h before or coffee/caffeine related
      beverages 3 h prior to the experiments are given. The participants are informed of the
      research, provide written consent to participate to the study and have a possibility to get
      acquainted with the experimental conditions. A questionnaire inquiring of the health and
      lifestyle of the participants is filled in. Following this the body composition of the
      subjects is assessed by bioimpedance. A baseline blood sample is drawn. After this the
      subjects are equipped with skin temperature thermistors and arm cuff (BP). ECG-electrodes are
      attached both for online (12-lead) and long term (24 h) monitoring of cardiac function.
      Subjects are followed in neutral conditions for 15 minutes (baseline). Continuous
      beat-to-beat BP, central aortic blood pressure and flow mediated dilation is recorded before
      the exposure to neutral/cold temperature and rest/exercise. For exercise in the cold the
      subjects are equipped with winter clothing and enter the experimental conditions (wind
      tunnel). During the exercise cardiovascular functions are followed continuously through the
      real-time ECG. BP is measured every third minute at rest and during exercise. Physical strain
      is assessed at 1- minute and thermal sensations at 5-minute intervals. The termination
      criteria include an ST-depression of more than 2 mm, symptoms of angina, as well as a sudden
      considerable change in BP. The termination of an experiment is decided by the paramedic nurse
      monitoring and medical doctor supervising the experimental session. After ending the exercise
      the cardiovascular functions are followed for 30 minutes at 22°C. A blood sample is taken
      immediately after the exercise. Continuous and central BP is measured 3-8 minutes following
      the exercise (early recovery) and after 15-20 minutes (delayed recovery). The subjects return
      48-hours after the experiment for providing a blood sample which enables to examine both
      immediate and delayed effects on hematological parameters (blood coagulation factors,
      inflammation markers, endothelin).

      Research environment and researchers

      The research is coordinated by the Center for Environmental and Respiratory Health Research
      (CERH) at the University of Oulu and with co-operation from the Research Unit of Internal
      Medicine, Center for Machine Vision and Signal Analysis and Finnish, Institute of
      Occupational Health and Finnish Defence Forces. International co-operation includes the
      University of Texas Southwestern Medical Center and University of Maastricht. The experiments
      are conducted in the unique thermal laboratories of Kastelli Research Centre in Oulu with
      comprehensive and novel equipment for assessment of circulatory, respiratory, autonomic
      nervous system function and thermal balance. The research team is multidisciplinary and
      consists of experts of sports sciences, physiology, medicine, rehabilitation, and wellness
      technology.

      Adjunct professor Tiina Ikäheimo (former Mäkinen), Ph.D., lecturer CERH, University of Oulu;
      PI of the research and with special expertise in physiology and the effects of temperature on
      human health and performance. The PI has produced several original publications and reviews
      and produced texts to national and international professional books (e.g. for WHO) of
      cold-related health risks and recommendations for their prevention.

      Research group:

      Professor Heikki Huikuri, MD, Ph.D., University of Oulu and Oulu University Hospital,
      Research Unit of Internal Medicine, Leader of Medical Research Center and expert in
      Cardiology; Adjunct professor Antti Kiviniemi, Ph.D., senior scientist of Exercise and
      Medical Physiology; Medical specialist in Cardiology, Juha Perkiömäki, MD, Ph.D.; Adjunct
      professor Mikko Tulppo, Ph.D.; Adjunct professor Arto Hautala, Ph.D. Center for Machine
      Vision and Signal Analysis, University of Oulu; Professor Markku Alén, MD, Ph.D., University
      of Oulu, Center for Life-Course Epidemiology (CLCE); Professor Hannu Rintamäki, Ph.D. Finnish
      Institute of Occupational Health; Professor Matti Mäntysaari*, MD, Ph.D., Director,
      Aeromedical Centre, Finnish Defence Forces; Professor Jouni J.K. Jaakkola, MD, Ph.D.,
      Director, CERH, University of Oulu; Postgraduate student Heidi Hintsala, Master in Health
      Sciences (MHSc). CERH, University of Oulu; Professor emeritus Juhani Hassi, Ph.D. CERH,
      University of Oulu; Doctoral student Rasmus Valtonen, CERH University of Oulu; Paramedic
      nurse Miia Länsititie, CERH, University of Oulu, Project secretary Riitta Aittamaa, CERH,
      University of Oulu. INTERNATIONAL: Professor Craig Crandall, Ph.D., Division of Cardiology,
      Department of Internal Medicine, The University of Texas Southwestern Medical Center, USA.
      Professor Wouter van Marken Lichtenbelt, Ph.D. Health, Medicine and Life Sciences, Human
      Biology, Maastricht University, Netherlands.

      Ethical questions

      The study follows the declaration of Helsinki and the legislation, decrees and ethical
      principles concerning medical research on humans in Finland. The study has been approved by
      the Northern Ostrobothnia Hospital Districts Ethical Committee. The experimental tests are
      performed under the monitoring of a paramedic nurse and supervision of a medical doctor.
    

Intervention name(s): Exercise/Rest and cold/neutral temperature
Intervention type(s): Other
Intervention description(s): Subjects were either exercising or resting in either cold or neutral environmental temperature
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Exercise; Cold Temperature