cardiovascular fitness -- a new vital sign??

A recent scientific statement from the American Heart Association stresses the importance of assessing cardiorespiratory fitness (CRF) as part of the risk assessment for cardiovascular disease (see cardioresp fitness importance circ2016 in dropbox, or DOI: 10.1161/CIR.0000000000000461)​.

Details:

-- Studies  since the 1950s have consistently found that CRF is a strong and independent marker of cardiovascular risk as well as all-cause mortality, adjusting for age and the other standard risk factors. This is been found in healthy men and women, those with known or suspected cardiovascular disease, and those with the co-morbidities of obesity, type 2 diabetes, hypertension, and hyperlipidemia. In many studies CRF is a more powerful predictor of mortality risk than traditional cardiovascular risk factors. It has even been shown to be a more powerful risk predictor than ST-segment depression, cardiovascular symptoms, or hemodynamic responses.
-- The survival benefit in 13 studies showed that each 1-MET (metabolic equivalent) higher CRF, a small increment, was associated with a marked 10-25% improvement in survival. And, one study found that men who improved from unfit to fit between two successive examinations had a reduction in mortality risk of 44% relative to those who remained unfit in both exams (ie, those with higher CRF have dramatic clinical benefit)
-- as a quick guide to METs:
    --light activity (<3 METs): includes walking 2.5 mph (2.9 METs)
    --moderate activity (3-6 METS): includes walking 3.0 mph (3.3 METs), walking 3.4 mph (3.6 METs), stationary biking (light effort) 5.5 METs
    --vigorous activity (>6 METs):  jogging (7.0 METs), calisthenics/pushups/situps (8.0 METs), rope jumping (10.0 METs)
-- of note, even though the most dramatic differences in all-cause and cardiovascular mortality were found comparing the most fit to the least fit subjects (70% and 56% respectively), the greatest increase in mortality benefit was in comparing the least fit group to the next least fit category
-- a recommendation in the paper is that CRF should become an accepted "vital sign", and should be part of the standard clinical encounter
-- CRF also is associated with heart failure exacerbations and mortality, with one study finding that for every 6% increase in CRF over three months there was a 4% lower risk of cardiovascular mortality or hospitalization, and an 8% decrease risk of cardiovascular mortality or heart failure hospitalization (for example, see http://gmodestmedblogs.blogspot.com/2016/09/vigorous-exercise-helps-those-with.html  which shows the benefit of vigorous exercise in patients with heart failure and reduced ejection fraction), timing of cardiac transplantation, preoperative surgical risk prediction (including studies of abdominal aortic aneurysm repair, liver transplant, lung cancer resection, upper GI surgery, intra-abdominal surgery, bariatric surgery, coronary artery bypass grafting). And interventions seem to help: in patients waiting for CABG surgery, those randomized into an exercise training group had superior outcomes to the control group, with a reduced rate of perioperative complications and shorter hospital stays. and observational studies have also shown that men with higher CRF had 68% lower stroke mortality, controlling for standard risk factors.
-- There were a few studies showing that those with a higher level of CRF had a reduced risk of developing dementia or Alzheimer's, one study showing a 36% lower risk of developing dementia in those with the highest quartile of CRF. Higher levels of CRF are also associated with lower measures of anxiety or depression symptoms
-- many studies have shown decreased risk of development of prediabetes, metabolic syndrome, and type 2 diabetes in those with higher CRF, again with the biggest difference in those going from lower CRF to the moderate range.
-- Lower levels of CRF at a younger age are also associated with a higher risk of disability at an older age. For example one study of obese adults with type 2 diabetes found that after four years, improvement of CRF decrease the likelihood of developing disability
-- Added value of CRF to the traditional risk calculators:
    -- several analyses have looked at various ways of incorporating the additional value of CRF. In one 30-year study of patients with stage II hypertension, the 30 year risk of cardiovascular mortality was 18.4% in those with low CRF versus 10.1 present in those with high CRF (ie, a huge difference)
    -- Overall, adding CRF to the traditional risk stratification led to actual CVD and all-cause mortality outcomes being correctly reclassified through the risk predictor as being decreased 23.3% and 20.6% respectively through correctly reclassifying patients as higher risk, and 55.8% and 46.0% respectively for correctly reclassifying patients as lower risk. The overall changes reflected a 30.5% and 24.5% correct reclassification for all-cause mortality, with larger changes in correctly reclassifying patients as lower risk because of CRF. [ie, those at apparently high risk by a traditional risk calculator, in reality have significantly lower risk if they are more fit; there are changes apparent in the other direction as well, but less emphatically so]. Also as a point of comparison, when looking at the nontraditional risk factors, such as coronary artery calcium scores  (which seems to be the best of the lot), the level of correct reclassification from the traditional risk calculators is much lower
-- so, how does one measure CRF?
    -- The most accurate and standardized quantification of CRF is through CPX (cardiopulmonary exercise testing), a combination of conventional exercise testing with ventilatory expired gas analysis
    -- a step below that is to look at achieved treadmill speed/grade and duration, making sure the patient does not hold the hand rails
    -- another approach is to look at submaximal exercise testing or the 6-minute walk test to assess distance walked (walking <350 meters is associated with high risk).
    -- And the easiest overall/least time-consuming/cheapest/easiest to implement is to do nonexercise prediction calculations. These are not standardized at this point, and each study seems to have somewhat different calculators. Perhaps the best is to use the one by Nes BM. Med Sci Sports Exerc 2011; 43: 2024 (or see exercise risk predictor questionnaire MedSciSportsExerc2011 in dropbox), which incorporated an assessment of patient reported physical activity, age, waist circumference, and resting heart rate, and this is one of the studies which included a lot of people (n= 2067 men and 2193 women) and looked at actual clinical outcomes, finding  that 90.2% of women and 92.5% of men in the lowest two quartiles of fitness were correctly classified. their questions for physical activity included: frequency of exercise (never, <1x/wk, 1x/wk, 2-3x/wk, >3x/wk), intensity ("no sweat/heavy breathing, "heavy breath and sweat", "push myself to exhaustion"), and duration (<15 in, 15-30 min, 30-60 min, >60 min).
-- overall exercise recommendations:
    -- type: exercise should involve major muscle groups (legs, arms, trunk) that is continuous and rhythmic (e.g. brisk walking, jogging, cycling, swimming, rowing)
    -- intensity: moderate and/or vigorous intensity relative to the persons capacity
    -- frequency: at least five days per week of moderate or three days per week of vigorous intensity exercise
    -- time: 30 to 60 minutes per day (150 minutes per week) of moderate and 20 to 60 minutes per day (75 minutes per week) of vigorous exercise. Of note between 10 and 20 minutes can be beneficial in previously inactive people
    -- amount: a target of 500 to 1000 MET-min/wk
    -- pattern: one continuous session per day or multiple sessions per day of greater than 10 minutes each. Less than 10 minutes may work in deconditioned individuals.

commentary:
-- incorporating CRF reflects a more individualized physiologic approach (assessing the constellation of how well the heart, lung, circulation, and oxygen extraction by muscles works). It is clear from epidemiologic data that on a community basis, as well as individual basis, the traditional risk factors of smoking, hypertension, hyperlipidemia, and diabetes confer an increased risk of cardiovascular disease. However, CRF is a truly specific individual physiologic risk factor, reflecting how these risk factors and more play out in the individual's body. For example, hypertension itself confers different levels of individual risk dependent on CRF.
--one note of caution: there is no uniformity in clinical practice as to which of the traditional risk calculators is the best: the Am Heart Association/Am College of Cardiology just published an updated tool, including a spreadsheet calculator (see cad prediction tool AHA2016 in dropbox, or doi.org/10.1161/CIR.0000000000000467 for the article, and http://circ.ahajournals.org/highwire/filestream/234917/field_highwire_adjunct_files/0/Appendix_Users_Guide_Spreadsheet.xls for the spreadsheet to calculate risk. BUT, this tool also needs to be validated in different populations prior to being accepted (also, see http://gmodestmedblogs.blogspot.com/2015/07/comparison-of-2013-accaha-lipid.html  for a critique of the 2013 ACC/AHA lipid guidelines.)
-- Interestingly, several studies suggest that CRF is a more potent predictor of cardiovascular disease than any of the individual risk factors we have incorporated into our predictive models
-- why is CRF so important? There are several explanations: improved traditional cardiovascular risk profiles (though most of the studies did control for the major ones we know), changes in autonomic tone that may reduce arrhythmogenic risk, fewer thrombotic events (exercise decreases fibrinogen levels, for example), improved endothelial function, lower levels of visceral adiposity/improved insulin sensitivity, lower levels of inflammation, as well as perhaps improved mental health and sense of well-being. And, there might be important positive changes in the gut microbiome with exercise, which is clear in animal models, less clear in humans where those who exercise tend to eat differently from those who do not, so hard to control well).
-- I should add a couple of caveats here: it is important not to confound fitness with doing lots of exercise; a significant component of fitness (on the order of 30+%) is genetic and not related to regular exercise. And most of the studies above are observational, not intervention studies (ie, only a few actually randomized patients to exercise programs vs none and looked at long-term outcomes. Though the one on pre-surgery exercise programs was pretty impressive. And, the overall data on the benefits of exercise overall are quite robust)
-- For ballpark figures, those with a CRF level less than 5 METs have a particularly high risk of mortality, whereas those with CRF levels of greater than 8 to 10 METS seem to have much
more protection. And, more than half the reduction in all-cause mortality occurs between those who are least fit (e.g. CRF less than 5 METs) and those in the next least fit group (e.g. CRF 5-7METS); ie, benefits for cardiorespiratory fitness are particularly strong in those people in the least fit as compared to the next higher category (i.e., one does not need to be an Olympic athlete to achieve the benefits)

so, the key points here are:
    -- cardiorespiratory fitness is an independent in additive risk assessor for total and cardiovascular mortality
    -- improving CRF dramatically decreases cardiovascular and all-cause mortality
    -- this clinical improvement is especially profound in those who are the least fit, finding a greater than 50% risk reduction by moving one step up to the next least fit group. An increase in CRF of only one MET is associated with the 10 to 20% decrease in mortality rate
    -- there is a reasonable argument based on studies that have been done to propose that a simple, non-exercise based calculator should be added as a vital sign. This could easily be measured by nonclinical staff and would provide clinicians important information to help encourage patient-specific exercise programs. this should to be evaluated more completely in different populations to assess its generalizability. However, even without those studies, given the documented benefits of exercise and the dramatic relationship in the above studies of CRF as a risk predictor, I personally will ask patients about CRF more and further reinforce the importance of exercise as part of a healthy lifestyle.

for other blogs on exercise, see http://gmodestmedblogs.blogspot.com/search/label/exercise