Several ageing-related cardiovascular diseases (CVDs) are triggered by changes in the arterial phenotype ^[1][2][1,2], such as the stiffening of large elastic arteries and endothelial dysfunction, which are independent predictors of forthcoming CVDs [3]. Given the high prevalence of ageing-related vascular disorders in males and females ^[4][5][4,5], promoting vascular health and preventing the development of CVDs in middle-aged (40–60 years) and older adults (60 years or older) is critical for public health.

Based on recent reports from the American College of Sports Medicine, there is a growing demand for health-oriented physical exercise for specific populations in Europe and the world, including among middle-aged and older adults ^[6][7][6,7]. The latest World Health Organization guidelines highlight and reaffirm the beneficial role of physical activity in the general health of older adults [8]. Indeed, the role of exercise in reducing risk factors for CVD and preventing viral infection diseases (in particular by SARS-CoV-2) in middle-aged and old adults is well-established ^{[9][10][11][12]}[9,10,11,12]. However, the positive impact of exercise is not only circumscribed to changes in CVD risk factors. Current evidence indicates a direct impact of exercise on arterial function (e.g., anti-atherogenic and anti-oxidative stress effects), mainly due to repetitive exposure to hemodynamic stimuli, such as shear stress and transmural pressure ^{[13][14][15][16]}[13,14,15,16]. In this sense, exercise represents a promising approach to preventing/managing vascular dysfunction, particularly in middle-aged and older adults [17]. Exercise is a highly versatile non-pharmacological tool with few contraindications and minimal side effects [18]. Yet, the available literature on exercise and vascular function in older populations is relatively scarce. Most of the accumulated evidence is based on exposure to endurance exercise [19]. Nonetheless, few studies directly compared the same endurance exercise mode performed at different exercise intensities ^[20][21][20,21]. On the other hand, the effects of resistance and stretching training on vascular function remain poorly explored.

Given vascular senescence is typically accompanied by functional (physical and cognitive) limitations [22], investigating the potential benefits of diverse types of exercise in this population is critical. Despite the evidence indicating that exercise training represents an effective strategy to promote vascular health ^[13][23][13,23], there are inconsistent data on the effects of chronic exercise on the vascular function of middle-aged and older adults. In addition, the magnitude of structural arterial adaptation (e.g., measured through the flow-mediated dilatation) to distinct characteristics of exercise (e.g., intensity, volume), as well as exercise-induced changes in different vascular regions (e.g., central vs. peripheral), have been poorly characterized and investigated. Therefore, it is relevant to identify and systematize the primary benefits of exercise training on vascular function and characterize the training regimens to allow fine-tuning the exercise prescription based on safety and effectiveness.

2. General Characteristics of the Population

Ageing-related arterial maladaptation is a major risk factor for CVDs ^[24][95]. Therefore, understanding the exercise contributions to the age groups most vulnerable to ageing-related vascular changes is essential. Regular exercise appears to be the most effective non-pharmacological prophylactic/therapeutic strategy against ageing effects on vascular health regardless of sex ^[17][25][17,96]. However, the current literature presents a considerable gap in investigating the vascular response of middle-aged and older adults to exercise. Considering studies in populations over 75 years old, classified as old-old (75–94 years) and oldest-old (over 95 years) ^[26][97], the results revealed a lack of studies in these age groups. None of the studies included individuals over 72 years of age. This might be a consequence of the clinical characteristics usually associated with the ageing process, such as physical/cognitive decline, and frailty ^[22][27][28][22,98,99]. Such characteristics demand specific exercise interventions to meet the specific needs of these populations ^[22][27][28][22,98,99]. For instance, endurance and resistance exercises require functional and motor skills that are frequently incompatible with the physical-functional status of older individuals ^[27][28][98,99]. In this sense, less motor complex, and effort-demanding exercise interventions, such as stretching exercise, have emerged as an alternative to promote vascular health in middle-aged and older adults. Most of the included studies investigated the vascular impact of exercise in middle-aged adults in mixed populations of males and females. However, rising evidence reveals that the progress of vascular ageing in females may follow a different chronology than in males, likely due to the role of sex hormones in the modulation of vascular (dys)function ^[29][30][31][100,101,102]. Yet, only middle-aged studies were composed of women.

3. Endurance Training

Studies with endurance exercise interventions showed the highest number of vascular benefits (29 studies). Among them, the benefits of aerobic training on vascular function were mostly in macrovascular outcomes. Endurance training was particularly effective in decreasing PWV (seven studies) and increasing FMD (20 studies). FMD is a well-established measure to assess the future risk of cardiovascular disease, being suggested as an independent predictor of cardiovascular events in different populations ^[32][33][34][103,104,105]. Likewise, PWV is the gold-standard method for arterial stiffness evaluation and a predictor marker of cardiovascular events in several clinical conditions such as heart failure, hypertension, and pulmonary hypertension ^[35][106]. Therefore, the modulation of these vascular health indicators represents a reduction in the risk of cardiovascular adverse events and diseases. Endurance interventions reporting vascular function benefits applied low- (eight studies) ^{[36][37][38][39][40][41][42][43]}[31,39,50,66,80,81,83,84], moderated- (seven studies) ^{[44][45][46][47][48][49][50]}[43,46,58,59,74,82,92], high- (six studies) ^{[46][49][51][52][53][54]}[53,58,75,77,82,89], and the moderated-high- (five studies) ^{[42][55][56][57][58]}[33,63,65,83,87] intensity of exercise. Endurance training also showed benefits on other vascular markers such as IMT (one study) ^[59][45]. However, this type of exercise was not effective in modulating other markers of the macrovascular function such as ABI, ALX, and CAVI at all exercise intensities, no studies reported any benefit of endurance training on these markers ^{[37][42][43][50][52][60][61][62][63][64]}[39,44,55,71,72,75,83,84,86,92]. These markers are predictors of heart and vascular diseases commonly linked to ageing, such as arterial stiffness and atherosclerotic and coronary heart disease ^[65][66][107,108]. The benefits of endurance training on microvascular function were less investigated and the least reported by the studies (seven in 29 studies) ^{[45][67][68][69][70][71][72]}[42,46,47,54,61,64,79]. Positive effects of endurance training on SNP (three studies) ^[45][68][71][46,47,64], ACh (five studies) ^{[67][68][70][71][72][73]}[37,42,47,61,64,79], and RH (one study) ^[69][54] were reported. Comparing exercise intensities, a higher number of high-intensity endurance exercise studies reported benefits in microvascular function outcomes (five studies) ^{[69][70][71][73][74]}[37,40,54,61,64]. Nevertheless, microvascular benefits were also reported in studies with moderated- (one study) ^[45][46], and low-intensity exercises (two studies) ^[67][68][42,47]. The vascular benefits of endurance training have been usually associated with relative intensity ^[75][109]. It has been suggested that high exercise intensities can induce greater shear stresses and more prominent vascular-related adaptations ^[76][110]. However, according to ACSM, high-intensity exercise may be particularly provocative for triggering negative cardiovascular events ^[77][111]. A substantial number of studies with low-intensity endurance exercise reported positive effects on at least one indicator of macrovascular function, suggesting such intensity is also effective in improving vascular function.

4. Resistance Training

Resistance training is a widely recommended non-pharmacological tool for preventing sarcopenia, osteoporosis, lifestyle-related diseases (e.g., diabetes), and maintaining and/or improving overall physical condition in middle-aged and older adults ^[78][112]. Resistance training is also known to reduce CVDs risk factors ^[79][113] but the mechanisms by which it reduces CVDs risk are still unclear. Although the potential benefits of resistance training on vascular function is a consistent hypothesis in the literature ^[80][114], the current evidence is still controversial and limited. Approximately half of the studies reported some or no vascular benefit from resistance training (six studies reported improvements and seven studies indicated no benefits). Only macrovascular benefits from resistance training were reported. Among macrovascular outcomes, resistance training was effective in modulating FMD (three studies) ^[54][81][82][36,76,89], PWV (two studies) ^[56][83][56,63], and ALX (one study) ^[84][69]. However, it was not possible to identify the most effective exercise intensity, since beneficial effects were reported by studies with four different exercise intensities, but with similar frequency (low- ^[83][84][56,69], moderated- ^[81][36], moderated-high- ^[56][82][63,76], and high-intensity ^[54][89]). Such results seem to indicate that rather than exercise intensity, the frequency of the resistance training seems to be relevant to improve vascular function. Indeed, high-intensity resistance training has been associated with an increase in arterial stiffness markers in both normotensive and hypertensive adults ^[85][115]. Since vascular function is closely linked with the sympathetic nervous system, it has been reported that resistance training might increase arterial stiffness due to its strong sympathetic vasoconstrictive effect on arterial walls. The resistance training-related factors that contribute (or do not) to promoting vascular function are complex and the vascular adaptation mechanisms underlying resistance training are still not fully understood ^[86][116]. It is speculated that the mechanical compression of the vessels followed by the release of blood flow during resistance training seems to respectively induce transient ischemia and subsequent hyperaemia increasing local shear stress ^[86][116]. More studies are needed to investigate the mechanisms of vascular response to resistance training and optimize the prescription of this type of exercise to promote vascular health. However, cuthe prrent evidenceesent review suggests that resistance training seems effective in positively modulating macrovascular function as half of the studies reported some positive effects on markers of macrovascular function, mostly decreasing PWV and increasing FMD. Given that no studies reported microvascular benefits, resistance training does not seem efficient in promoting microvascular function at any exercise intensity.

5. Combined Exercise Training

Combined exercise interventions showed a significant number of vascular benefits. Seven ^{[54][87][88][89][90][91][92]}[34,49,52,62,78,85,89] of eight studies reported some beneficial vascular effects from combined exercise intervention. Only one study of moderate-high intensity combined exercise did not report any effect on vascular function ^[93][60]. As observed in the interventions of other types of exercises, macrovascular function outcomes were the most frequently analysed, being reported in seven studies ^{[54][87][89][91][92][93]}[34,52,60,78,85,89], while only one study ^[88][49] examined the microvascular function outcomes. Among the studies analysing the effects of combined exercise on macrovascular function, six reported positive effects, namely on PWV (three studies) ^[90][91][92][62,78,85], FMD (two studies) ^[54][89][52,89], IMT (one study) ^[91][78], and ALX (one study) ^[87][34]. Among the exercise intensities from the studies showing beneficial macrovascular effects are moderated-intensity (five studies) ^{[54][89][90][91][92]}[52,62,78,85,89], followed by high- (two studies) ^[91][78], and low-intensity (one study) ^[87][34] exercise. In contrast, only one study ^[88][49] looked at the impact of combined exercise of high-intensity on microvascular function outcomes, which revealed a positive modulation of the SNP and RH indicators. SNP is a commonly used vasodilator in pharmaceutical therapies and research to assess vessel dilation capacity in response to nitric oxide ^[94][117]. Along with RH, it is a significant indicator of microvascular and endothelial function ^[94][117]. The cuprrent evidenceesent review suggests that the combination of endurance and strength exercises is the most effective exercise combination for promoting vascular health since all studies showing positive vascular effects of exercise utilised this combination of exercise. Indeed, current literature suggests that the combination of endurance-and resistance-type exercises is associated with the improvement, or at least stabilization, of arterial stiffness markers in older adults ^[95][118]. Combined exercise training (compared to other modalities such as strength training and under the most recent international guidelines) has been identified as the most effective modality in improving different cardiometabolic parameters in adults, namely in adult populations with overweight or obesity ^[96][119]. However, the order in which endurance and resistance exercises are performed in combined exercise interventions may alter the vascular impact of this type of exercise ^[97][98][99][120,121,122]. More significant vascular benefits were reported when endurance training was performed after resistance exercises in middle-aged adults. Such results suggest that the order of execution in the combination of aerobic and strength exercises should be taken into consideration when prescribing combined training. However, more studies dedicated to examining the impact of different types and intensities of combined exercises are urgently needed.

6. Stretching Training

Interventions with stretching exercises also showed positive results in vascular function outcomes, with seven of eight studies ^{[100][101][102][103][104][105][106]}[41,48,68,70,88,90,91] describing some vascular benefits. The macrovascular function outcomes were the most reported among studies with stretching exercise interventions (six studies). Among them, five studies report some benefits ^{[100][101][102][105][106]}[41,48,68,90,91] regardless of intervention duration, training frequency, and training session duration. There was no predominance among the macrovascular function markers that most benefited from stretching exercises, with positive effects being reported on PWV (two studies) ^[100][101][41,48], ALX (two studies) ^[105][106][90,91], CAVI (one study) ^[100][41], and FMD (one study) ^[102][68]. Among the perceived intensities of stretching exercises, a higher number of vascular benefits were reported by stretching interventions with “minimal discomfort” intensity (four studies) ^{[100][101][102][103]}[41,48,68,70]. Only one study with “fairly light” perceived intensity of stretching exercise did not report any effects on vascular outcomes ^[107][38]. The mechanisms underlying the beneficial effects of stretching exercise on vascular function are unclear, evidence has suggested that fluctuations in the shear rate during repetitive administration of stretching exercises are effective stimuli in improving vascular function and blood flow control mechanisms ^[108][123]. Still, it is important to highlight that after stretching training cessation, the improvements related to the central mechanisms remain for approximately 6 weeks, while the gains related to the local mechanisms seem to have a more persistent duration ^[108][123]. Only two studies ^[103][104][70,88] investigated microvascular function outcomes and both reported beneficial effects of exercise. Both studies were particularly efficient in increasing RH-PAT at “minimal discomfort” ^[103][70] and “somewhat heavy” ^[104][88] intensities of stretching exercise. RH/RH-PAT is a well-established method for the non-invasive assessment of microvascular (peripheral) function and a well-accepted predictor of all-cause and cardiovascular morbidity and mortality ^[109][124]. Despite the low number of studies dedicated to assessing the impact of stretching exercises on microvascular function outcomes, the results are promising. Stretching exercise protocols have recently gained attention from researchers as an ascending exercise alternative to promote vascular health, especially among older adults ^{[108][110][111]}[94,123,125]. This type of exercise is highly versatile and feasible to implement in community-dwelling middle-aged and older adults ^[112][126]. Additionally, above all, stretching exercise protocols do not require highly specialized spaces and significant financial investment. Overall, stretching exercise interventions were effective in promoting macro- (modulating CAVI, FMD, PWV, and ALX) and microvascular function (increasing RH-PAT), particularly at low perceived exercise intensities classified as “minimal discomfort”.