Introduction
cardiovascular exercise regimes for middle aged sedentary people
research

exercise for health

Introduction

regular exercise is critical to maintain cardiovascular health, reduce chronic disease risks including cancer and improve mental health
ideally there should be a variety of exercise types undertaken regularly such as walking, walking up hills or stairs, and resistance training with weights or similar
care must be taken though to avoid injury from exercise which can then make exercise levels difficult to achieve
cardiovascular fitness requires aerobic exercise rather than resistance exercise but high intensity aerobic exercise should only be newly undertaken in those over 35yrs after consideration of coronary risks to reduce sudden deaths
- timing of exercise may be important as cardiovascular events are more likely to occur soon after wakening¹⁾
- the 13 year prospective Isfahan Cohort Study in Iran suggested that only occupational physical activity reduced mortality, not leisure time activity - but this does not seem to be logical to me and I would think it needs substantive validation from more studies²⁾
- a prospective 2026 Australian study³⁾ of 58,000 women suggests that women who moderate exertion exercise 150min/wk (eg. 30 minutes of brisk walking five days a week) halve their mortality rates
- a study published in 2026 suggests those who do 4% of total exercise as vigorous had 29% to 61% lower risk of all outcomes than those with 0% vigorous and any vigorous activity could potentially prevent 21.4% of CRD, 32.3% of dementia, and 20.3% of IMID cases relative to 0% vigorous⁴⁾
resistance training is important
- optimizing muscle mass and bone mass to reduce frailty and osteoporosis fracture risks needs resistance exercise
- long term 2hrs of resistance training per week in women reduced cardiovascular and neurological mortality, no additional benefit was observed above 120 min/week, but the 2hr benefit was additive to benefits of aerobic training durations up to 45 MET-hours/week of aerobic activity⁵⁾
the better the quality of chest and back skeletal muscle (with less fat) in middle age on CT scan - the lower the risk of heart attacks and 10 year mortality
- for every 10-point increase in scan brightness, indicating better quality muscle with less fat in it, a person was calculated to be 31 percent less likely to have a heart attack. They were also 39 percent less likely to die in the 10 years after having the scan⁶⁾
unfortunately exercise appears to have minimal direct benefits to osteoarthritis⁷⁾ but maintaining muscle and bone mass are still important reasons to exercise
exercise at over 130MET-min/wk helps reduce steatohepatitis (fatty liver) with maximum effect seemingly attained by 850MET-min/wk⁸⁾

as with foods, moderation in most things is probably the best approach to exercise
- not enough is clearly bad for you
- too much is probably going to be bad for you

a 2025 systematic review of 31 studies (many not well powered) involving 160,000 adults suggests that walking 7000 steps a day has substantial health improvements:⁹⁾
- 47% reduction in all cause mortality
- 28% reduction in falls
- 25% reduction in cardiovascular disease (this reduction further improved with more steps walked)
- 22% reduction in depression
- 14% reduction in type II diabetes
- may reduce dementia and cancer
even modest step counts (around 4,000 steps per day) are linked to better health compared to very low activity (around 2,000 steps per day)
other than for cardiovascular benefits, walking more than 7000 steps had less significant additional benefits for most conditions than just 7000 steps making this a more realistic goal than 10,000 steps
another 2025 study showed that walking fast for 15 minutes a day reduced mortality of those aged 40-79yrs by 20%¹⁰⁾
a prospective study of 2,431,318 person years published in 2026 suggests even light-mod exercise reduces mortality, optimally at 5 metabolic equivalent task hours per week, and walking is amongst the most beneficial (swimming is least beneficial), while higher levels of exercise may be associated with increased mortality compared to less than 5 MET hours exercise a week (especially swimming, jogging and cycling) ¹¹⁾

Source: 2026: BMJ. Physical activity types, variety, and mortality: results from two prospective cohort studies

NB. MET is the metabolic rate for an activity / resting metabolic rate hence light walking is 2-2.5MET, brisk walking is 3.5-4.5MET, climbing stairs is 8-9MET, descending stairs is ~2.9MET, slow jogging 7-8MET, running at 11kph 11-12MET (faster can get to 20MET), cycling < 16kph 3-4MET 16-20kph 6-8MET, easy swimming laps 5-6MET, fast swimming laps 8-10MET;

too much exercise may be bad for you
- for some activity types such as swimming, jogging and cycling, higher levels of exercise over 5 MET hours exercise a week may be associated with increased mortality compared to less than 5 MET hours exercise a week ¹²⁾
- sudden cardiac arrest (presumably in those with unrecognised predispositions) may occur during or after a long run
- male endurance athletes (cyclists/triathletes) aged over 50 may be at much greater risk of serious heart problems¹³⁾
  - 25% experienced ventricular tachycardia during or just after exercising - usually non-sustained VT which may serve as warning sign for longer, more dangerous events, although 2.8% had sustained VT - all sustained VT were during or within 1 hr of exercise
  - 90% of sudden cardiac deaths during sport occur in older male athletes - 75% of these had heart scarring which may have been caused by heart attacks, disease, or exertion from lots of high intensity exercise over many years
- rates of sudden cardiac arrest are 20x higher in professional female body builders compared with amateurs and they also had a rate of suicide or homicide 4x higher than in male bodybuilders ¹⁴⁾
- a large UK study seems to show that women (with average age at recruitment of 55yrs) reporting strenuous physical activity daily had higher risks of coronary heart disease (P=0.002), cerebrovascular disease (P<0.001), and venous thromboembolic events (P<0.001) than those reporting doing such activity only 2 to 3 times per week¹⁵⁾
- while moderate exercise reduces AF risk, high volumes of endurance training over years may be associated with heart arrhythmias like atrial fibrillation
  - a 2025 study showed elite male rowers were seven times more likely to develop AF ¹⁶⁾
- moderate to high intensity exercise increases circulating cortisol levels which may have adverse effects¹⁷⁾
  - pre-season cumulative training loads alters cortisol levels, which may impair recovery, disrupt anabolic processes, and increase the risk of overtraining or injury - effective recovery strategies during pre-season are essential to mitigate elevated physiological stress responses and promote optimal training adaptation
  - high-stakes matches in female athletes reduce sleep quality and increase salivary cortisol by 354%
  - elevated post-exercise cortisol can suppress immune function, increase muscle protein breakdown, and disrupt sleep patterns, impairing performance and recovery
- over-training syndrome causes chronic fatigue, immune system impairment, mood disturbances, and performance decline
- in women, extreme exercise can suppress the hypothalamic-pituitary-ovarian axis, leading to anovulation and anovulatory menstrual cycles, low libido, osteoporosis risk and other issues
- psychological strain and burnout with emotional exhaustion, reduced motivation, and mental health disorders are common in elite athletes
- overuse injuries
- some people should only do restricted guided exercise as more intense exercise may be lethal
  - survivors of aortic dissection¹⁸⁾ or cardiac infarcts
  - some other cardiac conditions eg. Wellen's syndrome, aortic stenosis, Arrythmogenic Right Ventricular Dysplasia / Cardiomyopathy (ARVD/ARVC) without an ICD, cardiomyopathies, etc.
  - risk factors for AMI or sudden death (eg. previous exertional syncope or FH sudden exertional death) without appropriate risk stratification investigations
  - new DVT - theoretically could dislodge and form a massive PE
- excessive or poorly managed training may induce neuromuscular fatigue and mild chronic inflammation and chronic inflammation is a risk for atherosclerosis
- prolonged outdoor exposures to UV cause premature skin aging, solar dermatitis and skin cancer risk
- fortunately, other than skin cancers, there does not appear to be increased risk of other cancers due to consistence high level exercise
- many sports have characteristic long term musculoskeletal chronic effects such as:
  - hockey players: premature hip OA often requiring THR by age 50yrs
  - rugby, AFL: high prevalence of arthritis, dementia/Alzheimer’s disease, early onset osteoarthritis, and neurodegenerative conditions such as CTE due to repeated traumatic brain injuries
  - soccer: significant risk of traumatic knee and ankle injuries leading to early onset osteoarthritis and joint degeneration; heading the ball is now thought to cause repeated brain insults.
  - combat sports: shorter lifespan, likely from traumatic injuries.
  - volleyball and handball: shorter lifespan hypothesized due to severe musculoskeletal stress and physical trauma associated with the sport
  - long distance cycling: osteoporosis risk especially in women with amenorrhoea; tight hips and hamstrings; chronic pain commonly occurs in the neck, knees, and back due to repetitive strain and posture during cycling; high risk of road trauma; patellofemoral pain syndrome; numbness of hands or overuse tendonitis caused by weight-bearing on the handlebars; iliotibial band syndrome; rotator cuff tendonitis impacting shoulders; cervical disc prolapse risk, solar dermatitis and thickening on neck in particular;
  - mountain biking: high incidence of fractures, head injuries
  - swimming: chronic shoulder problems such as rotator cuff tendinopathy and impingement syndromes related to training volume and intensity;
- some professional sports appear to be associated with lower life longevity¹⁹⁾
  - studies are surprisingly difficult to have confidence with results, often due to small numbers, many may actually have short elite sports careers, and several mechanisms within and between sports may have powerful effects on the overall lifespan longevities of players (e.g., type of sport, playing position, race, and energy system)
  - most contact sports such as martial arts, wrestling, boxing although AFL football seemed to not have this negative effect
  - a 2020 meta-analysis failed to show any survival benefit for male power athletes but did show benefits for other male athletes in terms of cardiovascular deaths ²⁰⁾
  - some sports that require sudden movements which risk severe skeleto-muscular stress such as volleyball although strangely tennis did not - so perhaps there are other factors
  - ultra-distance running - presumably due to accelerated oxygen radical generation and oxidative stress
  - high risk sports such as mountaineering
  - most sports for female athletes (although golf seems to prolong life spans in women) - however research study numbers tend to be low for professional female athletes who have died

some people SHOULD NOT lift very heavy weights or do severe Valsalva manoeuvres
- those at risk of rupturing important blood vessels:
  - Berry aneurysms - risk of potentially lethal subarachnoid haemorrhage (SAH)
  - those with risk factors for potentially lethal aortic dissection, including survivors of aortic dissection
  - uncontrolled hypertension - may risk disabling or potentially lethal stroke (CVA)
- those who do not know how to lift heavy weights correctly or who have not adequately prepared themselves to be able to do so safely
  - high risk of chronic pain from vertebral disc prolapse either cervical or lumbar (and much less commonly, thoracic)
  - risk of tendon or muscle tears
  - risk of developing abdominal hernias without adequate precautions
- those who have underlying conditions predisposing to injury from heavy weight lifting
- those who already have injuries which may be exacerbated by such lifting

cardiovascular exercise regimes for middle aged sedentary people

ideally an exercise regime should have a mix of activities, the safest and most beneficial appear to be walking and walking up hills or stairs
it seems moderate weekly exercise of 90min/wk (eg. walking) is associated with nearly a 50% lower risk of AF recurrence following catheter ablation²¹⁾
it seems that one can reverse years of adverse cardiac effects from long standing sedentary lifestyles in the middle age by adopting an exercise program with the following minimal levels:
- it has to be something they have access to
- it has to be something they enjoy
- it has to be alternating impact and low impact, and each week:
  - at least one or two long sessions (1hr) of brisk walking, dancing or sport such as tennis
  - at least one or two high intensity aerobic sessions (20-30min) of walking up hills, etc.
  - at least two or three moderate exercise sessions which raise a sweat but not shortness of breath such as moderate walking
- yoga or weight lifting do not improve cardiovascular fitness, but each have their own benefits and risks if not performed with care

research

dimethylguanidino valeric acid (DMVG), exercise and health
- increasing exercise can lower levels of dimethylguanidino valeric acid (DMVG), a molecule in the blood linked to poor health outcomes BUT those with “more room to improve” – actually saw less benefit from exercise than people with lower baseline levels of DMVG – those in better health to begin with. DMGV was associated with adverse metabolic risk even in very young individuals free of overt disease. DMGV levels may identify individuals who are less responsive to the metabolic health benefits of endurance exercise training and may require additional therapies beyond guideline-directed exercise to improve their metabolic health. ²²⁾
the α-actinin-3 protein gene (ACTN3)
- the α-actinin-3 protein is found in muscles important for explosive activities such as sprinting but is also for the androgen receptor in muscle tissue in both men and women and response to testosterone - at least 7 genes tat drive this effect depend on the α-actinin-3 protein for proper expression ²³⁾
- one in five people lack this protein due to inheriting two copies of the null variant (577X) in the ACTN3 gene
  - a common null polymorphism in ACTN3 (R577X) arose in modern humans and underwent positive selection ~10 to 15,000 years ago
  - among the elderly, α-actinin-3 deficiency is associated with significantly lower strength and higher frailty scores in an elderly Chinese population
myokines
- cytokines or other small proteins (~5–20 kDa) and proteoglycan peptides that are produced and released by skeletal muscle cells (muscle fibers) in response to muscular contractions
- receptors for myokines are found on muscle, fat, liver, pancreas, bone, heart, immune, and brain cells
- they are involved in exercise-associated metabolic changes, as well as in the metabolic changes following training adaptation
- they also participate in tissue regeneration and repair, maintenance of healthy bodily functioning, immunomodulation; and cell signaling, expression and differentiation
- eg, myostatin, irisin
mechanisms in resistance training
- intense resistance exercise induces acute myofibrillar damage and activates a specialized repair system that recognizes damaged muscle components and targets them for removal. At the same time, this repair machinery promotes the synthesis of new contractile proteins, replacing those that have been damaged. This coordinated process preserves and reinforces the muscle's contractile apparatus.²⁴⁾
  - regulation mainly affects the protein network linked to the muscle maintenance protein BAG3, which includes mechanosensory proteins, small heat shock proteins, and a lipid droplet associated protein
  - all network components exhibit altered phosphorylation and increased cytoskeletal association after damaging resistance exercise and network components cooperate to recognize strained skeletal muscle structures and mediate their degradation through chaperone-assisted selective autophagy (CASA)