Fitness: The “Secret” of Vascular Youth

A man is as old as his arteries This comment, made almost four centuries ago, absolutely conforms to the contemporary suggestion that arterial stiffness, which reflects the effects of aging, high blood pressure, and other cardiovascular (CV) risk factors on the arterial wall, is an independent predictor of CV morbidity and CV and all-cause mortality.1 Therefore, current therapeutic strategies aim towards the management of traditional CV risk factors, such as hypertension, dyslipidemia, diabetes mellitus, and metabolic syndrome in the effort to turn back the clock of vascular age.2-5 Nevertheless, the astute physician has to use every weapon of the therapeutic armamentarium in order to either attenuate arterial stiffening or “destiffen” the arterial wall. In this issue of the Journal, Gando and colleagues6 tested the hypothesis that higher cardiorespiratory fitness (CRF) would be associated with less progression of age-related arterial stiffening in healthy adults. The investigators recruited 470 healthy Japanese adults and conducted a 2-year follow-up study to examine the association between CRF and arterial stiffness progression. Study participants were distributed into tertiles based on their peak oxygen uptake (VO2max) levels during a graded cycle exercise test. Brachial-ankle pulse wave velocity (baPWV) was measured at baseline and 2 years later for the assessment of arterial stiffness. Anthropometric measures, body composition determined by dual-energy radiography absorptiometry, and exercise habits were recorded for each participant. The daily physical activity was evaluated by a triaxial accelerometer, which was worn during the day. In addition, the levels of glucose and glycated hemoglobin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides were determined in blood samples. The 2-year changes in baPWV were significantly higher in the low CRF group compared with those in the highest CRF group. Therefore, higher CRF was associated with slower progression of age-related arterial stiffening (measured by baPWV). In addition, CRF was inversely associated with 2 years of baPWV progression. Stepwise multiple regression analysis demonstrated that the inverse association between CRF and arterial stiffness was independent of other factors traditionally related to arterial stiffness. This is the first study to investigate the relationship between CRF and the rate of progression of baPWV in healthy adults in a longitudinal study. Previous cross-sectional studies have shown that a high level of CRF was associated with arterial stiffness. Thus, there is still only limited knowledge about the longitudinal relationship between CRF and the changes in baPWV. The main strengths of the study were the large sample size, the adequate follow-up period (2 years), and the use of maximal exercise testing for estimation of CRF levels, which has high accuracy and remains the gold standard for the measurement of CRF. On the other hand, there are some limitations of the study. First, there was a lack of CRF assessment at the end of the follow-up period, thus the effect of potential CRF changes during the 2-year period on arterial stiffness was not assessed. This is an important parameter since unfit individuals with improved fitness status had a 35% lower mortality risk (hazard ratio, 0.65; 95% confidence interval, 0.46–0.93) compared with those who remained unfit in a 20-year follow-up study of older male veterans.7 The same applies for leisure-time physical activity evaluation during the study, which was not recorded. Recently, Ferreira and colleagues8, 9 demonstrated that improving CRF and, more specifically, VO2max by increasing physical activity levels, seems to contribute to a reduction in mortality from CV disease. Second, study participants were rather young and healthy, devoid of established CV disease or CV risk factors, thus not permitting the generalization of study findings to other patient populations. Third, two different methods to analyze oxygen consumption and carbon dioxide production were used. Nevertheless, it has been demonstrated that the results from the two methods do not differ. Finally, the authors of the study admit that significant changes in arterial stiffness occur during the menstrual cycle. However, the number of premenopausal women who participated in the study was relatively low (36%) and they were equally distributed into three groups. CRF is a well-established risk factor for all-cause and CV disease and mortality in the general population, independently of established risk factors such as blood pressure, cholesterol, body mass index, and smoking.10-12 Moreover, exercise capacity has been proven to be strongly, inversely, and independently associated with all-cause mortality in a variety of clinical conditions, including hypertension, prehypertension, diabetes mellitus, and dyslipidemia.13-18 Substantial evidence has established that increased arterial stiffness, as assessed by PWV, represents a strong and independent predictor of CV morbidity and CV and all-cause mortality. A meta-analysis of approximately 16,000 participants in 17 longitudinal studies showed that there was a linear association between PWV and patient outcome.1 An increase in aortic PWV by 1 m/s was associated with an increment of 14% in total CV events, 15% in CV mortality, and 15% in all-cause mortality. Interestingly, the predictive value of arterial stiffness has been demonstrated among various populations, such as in the general population, in elderly people, and in patients with impaired glucose tolerance, diabetes, hypertension, or renal failure.5, 19, 20 It is also worth pointing out the ability of arterial stiffness to predict CV events above and beyond traditional risk factors, such as current smoking, age, sex, body mass index, hypertension, dyslipidemia, and diabetes.21-24 Given the correlation between arterial stiffness and coronary atherosclerotic lesions, it is essential to understand the role of lifestyle modification, such as aerobic exercise, and in general a fit and active way of life, and sodium restriction. Indeed, it seems to be an effective therapeutic intervention for preventing, delaying, or reversing the progression of arterial stiffening.25 Thus, lifestyle modifications are recommended as part of a first-line therapeutic approach for arterial stiffness.26 In conclusion, this was the first prospective longitudinal study to point towards an inverse association between CRF and the progression of aging arterial stiffness among healthy adults of all age categories (20–69 years). So far, relevant information was available only for adolescents and young adults (13–36 years).7, 8 Further studies are needed to reproduce and validate these findings in various populations (patients with CV disease and CV risk factors, such as diabetes, hypertension, and dyslipidemia). More importantly, it would be helpful to know whether the benefits of high CRF are maintained during longer follow-up periods, beyond only 2 years. Nevertheless, current data suggest that increased CRF may be an effective and reliable measure for attenuating age-related arterial stiffness.