Review
Preventive Effects of Physical Activity on the Development of Atherosclerosis: A Narrative Review
2025 Volume 32 Issue 1 Pages 11-19
Details
2025 Volume 32 Issue 1 Pages 11-19
Atherosclerosis, a major contributor to cardiovascular diseases (CVD), remains a leading cause of global mortality and morbidity. The pathogenesis of atherosclerosis involves a complex interplay of endothelial dysfunction, chronic inflammation, lipid accumulation, and arterial stiffness. Among the various preventive strategies, physical activity has emerged as a highly effective, non-pharmacological intervention. This review examines the preventive effects of different types of exercise—specifically aerobic exercise, resistance training, and combined training—on atherosclerosis development. Drawing on evidence from landmark studies, we explore the underlying mechanisms by which these exercise modalities improve endothelial function, reduce systemic inflammation, and enhance lipid profiles, thereby mitigating the progression of atherosclerosis. Additionally, the review discusses the dose-response relationship between physical activity and cardiovascular health, the differential effects of exercise intensities, and the potential risks associated with high-intensity training. The synergistic benefits of combined aerobic and resistance training are highlighted, particularly in populations with metabolic syndrome or other high-risk conditions. Emerging trends in personalized exercise medicine and the use of wearable technology for monitoring physical activity are also addressed, underscoring the potential for tailored exercise prescriptions to maximize cardiovascular health. By integrating current research findings, this review provides insights into effective exercise strategies for reducing cardiometabolic risk and emphasizes the importance of personalized approaches in exercise interventions.
Atherosclerosis is a leading cause of cardiovascular diseases (CVD) such as coronary artery disease (CAD), stroke, and peripheral artery disease. These conditions significantly cause all-cause mortality and morbidity, with cardiovascular disease being the leading cause of death worldwide. In fact, CVDs account for approximately 17.9 million deaths annually, representing 32% of all global deaths1). Additionally, the economic burden of atherosclerosis is also substantial. The World Health Organization reported in 2021 that healthcare costs related to cardiovascular diseases expected to exceed $1 trillion globally by 2030 1). The pathophysiology of atherosclerosis is implemented with a complex interplay of endothelial dysfunction, chronic inflammation, lipid accumulation, and arterial stiffness. Given its insidious onset and long-term progression, preventive strategies are essential for reducing the burden of this disease.
As several guidelines stated, physical activity has emerged as one of the most effective and modifiable non-pharmacological factors for the prevention and management of cardiovascular diseases2-4). The protective effects of habitual physical activity on cardiovascular health are well-documented, with numerous studies demonstrating that physical activity can reduce the risk of developing atherosclerosis and its associated complications. Despite the clear benefits of physical activity, there remains a need to understand the differential effects of various exercise modalities on atherosclerosis. Aerobic exercise, resistance training, and combined training each have unique impacts on the cardiovascular system, influencing atherosclerosis-related factors such as endothelial function, arterial stiffness, and systemic inflammation in different ways5-7).
The goal of this review is to provide an overview of the preventive effects of different types of exercise—specifically aerobic exercise, resistance training, and combined training—on the development of atherosclerosis. By exploring the mechanisms through which these exercise modalities exert their protective effects, this review seeks to offer insights into effective exercise strategies for reducing cardiovascular risk. Additionally, this review will describe future direction toward personalized exercise that maximize cardiovascular health protection. In the following sections, we will first describe the importance of habitual physical activity in preventing atherosclerosis, drawing on evidence from major observational studies. We will then delve into the specific effects of aerobic exercise, resistance training, and combined training on atherosclerosis development, discussing the mechanisms involved and highlighting key findings from recent research. Finally, we will address the implications of these findings for public health and clinical practice, emphasizing the need for tailored exercise prescriptions that account for individual differences in response to exercise.
The protective role of habitual physical activity against atherosclerosis is well-established through decades of research. The Framingham Heart Study (FHS) has shown that habitual physical activity is associated with a significant reduction in the risks for CAD and related mortality8, 9). Similar findings have been reported in the Nurses’ Health Study, which highlighted the role of habitual exercise in lowering the risk of stroke and coronary heart disease in women10). These landmark studies, along with others such as the Atherosclerosis Risk in Communities Study and the Women’s Health Initiative, have established a robust longitudinal association between physical activity and cardiovascular health11-14). Habitual physical activity is associated with improved endothelial function, reduced systemic inflammation, enhanced lipid profiles, and decreased arterial stiffness—all of which are key factors in preventing the development and progression of atherosclerosis5, 15-17). Notably, the FHS also indicated that recent physical activity levels are more crucial for reducing the risk of all-cause mortality and CAD compared to physical activity in the past, supporting the idea that it is never too late to adopt an active lifestyle for cardiovascular health18).
These observational studies underscore the critical impact of habitual physical activity on preventing the development and progression of atherosclerosis, particularly through mechanisms such as enhanced nitric oxide (NO) bioavailability, reduced oxidative stress, and improved lipid profiles19-21). Moreover, as atherosclerosis progresses, it causes a decline in cardiorespiratory fitness22). This decline is a significant concern because reduced cardiorespiratory fitness, as seen in the frailty cycle, leads to decreased physical activity, which in turn accelerates the progression of atherosclerosis23). This vicious cycle highlights the importance of maintaining cardiovascular health through habitual physical activity, as improved cardiorespiratory function not only helps prevent the onset of atherosclerosis but also encourages sustained physical activity, thereby breaking the cycle and mitigating further cardiovascular deterioration.
Dose-Response Relationship in Physical ActivityThe dose-response relationship between physical activity and atherosclerosis prevention is a well-established area of research, with substantial evidence supporting the cardiovascular benefits of moderate physical activity. Sattelmaire et al. conducted a meta-analysis that quantified the specific amounts of physical activity required for lower risks of coronary heart disease (CHD), finding that individuals who engaged in 150 minutes weekly of moderate intensity leisure-time physical activity had a 14% lower risk of CHD, while those who met the advanced guideline of 300 minutes weekly had a 20% lower risk24). Notably, even physical activity below the physical activity recommendation levels was associated with significant reductions in CHD risk. Similarly, Kyu et al. examined the relationship between physical activity and various health outcomes, including cardiovascular diseases25). Their findings reinforced the notion that higher levels of physical activity were associated with lower risks of these outcomes. These studies further emphasized that the protective effects of physical activity are robust across different populations.
The intensity and frequency of physical activity are critical factors in determining the degree of cardiovascular protection. Saladini summarized current literature on this topic, with highlighted that in hypertensive individuals, vigorous exercise may not confer the same benefits as it does in normotensive individuals7). Vriz et al. showed that while leisure-time physical activity was associated with a reduction in arterial stiffness, vigorous exercise did not yield the same benefits in hypertensive individuals, probably due to increased oxidative stress26). This finding suggests that while high-intensity exercise can offer substantial cardiovascular benefits, it must be carefully managed, particularly in individuals with hypertension to avoid potential adverse effects like increased arterial stiffness.
Understanding the mechanisms through which physical activity exerts its protective effects on the cardiovascular system is essential for optimizing physical activity prescriptions for atherosclerosis prevention.
2.1. Beneficial Effects on Endothelial FunctionAt the molecular level, physical activity influences a variety of cellular processes that contribute to cardiovascular health. One of the primary mechanisms is the physical activity-induced increase in blood flow and shear stress on endothelial cells16). This mechanical stimulus enhances the production of NO, a potent vasodilator that improves blood flow and reduces arterial stiffness16). NO also has anti-inflammatory properties that help protect the endothelium from oxidative stress and the accumulation of lipids27).
Exercise also upregulates the expression of antioxidant enzymes such as superoxide dismutase and catalase, which neutralize reactive oxygen species (ROS) and prevent oxidative damage to the vascular endothelium28). This reduction in oxidative stress is critical for maintaining endothelial function and preventing the initiation and progression of atherosclerosis, as oxidative stress plays a pivotal role in endothelial dysfunction and the development of cardiovascular diseases6). Moreover, physical activity-induced mobilization of endothelial progenitor cells (EPCs) contributes to vascular repair and further supports the preservation of endothelial health6).
2.2. Anti-Inflammatory Effects of Physical ActivityChronic inflammation is a key driver of atherosclerosis, and physical activity has been shown to have significant anti-inflammatory effects6). Physical activity induced interleukin-6 (IL-6) production that stimulates other anti-inflammatory cytokines such as IL-1ra and IL-10, inhibits the production of tumor necrosis factor-alpha (TNF-α) which help to mitigate the inflammatory response and protect against atherosclerosis29). The anti-inflammatory effects of physical activity are particularly important for individuals with metabolic syndrome or type 2 diabetes that are characterized by chronic low-grade inflammation and an increased risk of atherosclerosis30). By reducing systemic inflammation, physical activity not only slows the progression of atherosclerosis but also improves overall metabolic health30). Additionally, the reduction of inflammatory markers through habitual physical activity is associated with lower rates of plaque formation and plaque instability, which are critical factors in the prevention of cardiovascular events31).
2.3. Metabolic Effects of Physical ActivityPhysical activity plays a crucial role in regulating metabolic pathways that influence cardiovascular health. Physical activity improves insulin sensitivity, enhances glucose uptake by skeletal muscle, and reduces circulating levels of glucose and insulin32). These metabolic improvements are particularly beneficial for preventing the onset of type 2 diabetes and reducing the risk of atherosclerosis in individuals with pre-existing metabolic conditions32).
Furthermore, physical activity has a direct impact on lipid metabolism. Habitual physical activity increases high-density lipoprotein cholesterol levels, while reducing low-density lipoprotein cholesterol and triglycerides. These favorable changes in lipid profiles are key to preventing the accumulation of lipids in arterial walls and the subsequent development of atherosclerotic plaques32).
Aerobic exercise, encompassing activities such as walking, running, cycling, and swimming, is one of the most extensively studied forms of physical activity for cardiovascular health. The preventive effects of aerobic exercise on atherosclerosis are primarily mediated through improvements in endothelial function, reductions in systemic inflammation, and enhancements in lipid metabolism8).
3.1. Impact on Endothelial Function and Arterial StiffnessThe endothelium plays a critical role in maintaining vascular health, and aerobic exercise has been shown to significantly improve endothelial function6). Studies like those by Hambrecht et al. have demonstrated that moderate to vigorous aerobic exercise improves arterial stiffness and endothelial function33). These improvements are largely attributed to the increased bioavailability of NO, which enhances vasodilation and reduces oxidative stress16, 27). In addition to these benefits, aerobic exercise promotes the mobilization of EPCs from the bone marrow34). These cells play a crucial role in the repair and maintenance of the endothelial lining, thereby contributing to vascular health6). Enhanced EPC activity has been linked to reduced arterial stiffness and a lower risk of atherosclerotic plaque development.
3.2. Reduction in Systemic InflammationAerobic exercise has been demonstrated to reduce levels of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, which are key players in the inflammatory processes driving atherosclerosis. Recent studies emphasize the role of Sestrin 1 (SESN1), a stress-inducible protein, in mediating these effects. SESN1 has been shown to inhibit the activation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome, a critical component in the inflammatory response triggered by oxidized low-density lipoprotein (oxLDL) in macrophages, which plays a crucial role in the development of atherosclerosis35). Furthermore, SESN1 impedes the Nuclear Factor κB (NF-κB) signaling pathway, thereby reducing the expression of pro-inflammatory cytokines35). Additionally, aerobic exercise has been found to upregulate SESN1, leading to the suppression of Matrix metalloproteinases 9 (MMP9) and MMP13, enzymes that contribute to plaque instability in atherosclerosis36). These findings highlight the significance of SESN1 in the anti-inflammatory effects of aerobic exercise, suggesting it plays a pivotal role in stabilizing atherosclerotic plaques and reducing systemic inflammation.
Resistance training, including body weight exercise, is essential not only for maintaining muscle mass but also for enhancing metabolic health and potentially influencing cardiovascular outcomes. The effects of resistance training on atherosclerosis are multifaceted, with the impact varying depending on the intensity and type of exercises performed. While moderate-intensity resistance training is associated with protective cardiovascular benefits, higher intensities may yield different effects due to their influence on specific signaling pathways. Recent studies confirm that both dynamic and isometric resistance training can lead to significant improvements in endothelial function, which is crucial for cardiovascular health37, 38).
4.1. Impact on Vascular Function and Arterial StiffnessResearch indicates that moderate-intensity resistance training can improve vascular function and reduce arterial stiffness, particularly when combined with aerobic exercise. For example, studies have shown that resistance training performed at 50-70% 1 repetition maximum (RM) two to three times per week, significantly improves flow mediated dilation (FMD)37, 38). These improvements are mediated by the activation of AMP-activated protein kinase (AMPK), which plays a pivotal role in reducing endoplasmic reticulum stress (ERS) and ROS, thereby preserving endothelial function. Additionally, regular resistance training enhances the elasticity of peripheral arteries, contributing to improved blood flow and reduced blood pressure, particularly beneficial for older adults at increased risk of arterial stiffness and atherosclerosis37).
However, it is important to note that high-intensity resistance training may possibly increase arterial stiffness, especially in central arteries. This effect is likely due to the differential activation of signaling pathways at varying exercise intensities. For instance, the differential response of AMPK subunits (AMPKα1 or AMPKα2) to exercise intensity may explain the contrasting effects of moderate versus high-intensity resistance training on arterial stiffness38). Therefore, careful selection of exercise intensity may be crucial to maximize cardiovascular benefits while minimizing potential risks.
4.2. Role in Metabolic HealthResistance training is particularly beneficial for metabolic health, which is closely linked to cardiovascular outcomes. By increasing muscle mass, resistance training enhances glucose uptake and insulin sensitivity, reducing the risk of type 2 diabetes and its associated cardiovascular complications. This benefit is largely mediated through the SESN1-AMPK-mTORC1 signaling pathway, which regulates autophagy and inhibits inflammation, thus reducing the risk of atherosclerosis38). Furthermore, resistance training improves lipid profiles, further diminishing the risk of atherosclerosis.
Moreover, resistance training has been shown to increase basal metabolic rate, aiding in weight management and reducing the risk of obesity—a significant risk factor for atherosclerosis. The combination of increased muscle mass and improved metabolic health makes resistance training an invaluable component of cardiovascular disease prevention strategies. The protective effects on metabolic health also involve the regulation of mitochondrial function through pathways such as AMPK and Peroxisome proliferator-activated receptor γ (PPARγ), which are crucial for maintaining metabolic flexibility and reducing oxidative stress37, 38).
Combining aerobic and resistance training offers a synergistic approach that maximizes cardiovascular benefits while minimizing potential drawbacks associated with each exercise modality individually. Studies have demonstrated that combined exercise training improves endothelial function, reduces arterial stiffness, and enhances overall cardiovascular health more effectively than either aerobic or resistance training alone. For instance, combined aerobic and resistance training significantly reduced arterial stiffness and improved blood pressure in obese prehypertensive adolescent girls, highlighting its potential in early cardiovascular disease prevention39). Furthermore, systematic reviews and meta-analyses indicate that combined training is particularly effective in reducing cardiovascular risk factors, including waist circumference, fasting glucose, and lipid profiles in adults with metabolic syndrome40). This evidence supports the role of combined aerobic and resistance training in managing and preventing atherosclerosis across different populations.
5.1. Synergistic BenefitsThe HART-D study and other similar research underscore the significant cardiovascular and metabolic health improvements observed in individuals with metabolic conditions, such as type 2 diabetes or metabolic syndrome, who engage in combined aerobic and resistance training41). For example, studies have shown that combined aerobic and resistance training not only reduces arterial stiffness and systolic blood pressure but also improves insulin sensitivity39). Additionally, combined aerobic and resistance training has been shown to enhance cardiorespiratory fitness, an important factor in reducing all-cause mortality and cardiovascular events. Typically, this combined approach involves 150 minutes of moderate-intensity aerobic exercise per week, complemented by 2 to 3 sessions of resistance training targeting major muscle groups4).
The synergy between aerobic and resistance training lies in their complementary effects on cardiovascular and metabolic health. Aerobic exercise primarily enhances cardiovascular endurance and reduces systemic inflammation, while resistance training builds muscle mass and improves metabolic function. When combined, these modalities offer a comprehensive approach to reducing cardiovascular risk. Notably, combined exercise regimens have been shown to decrease levels of endothelin-1, a potent vasoconstrictor, and increase NO bioavailability, leading to improved endothelial function and reduced arterial stiffness39). In populations with peripheral arterial disease, the integration of exercise and optimized nutrition further amplifies these benefits, contributing to overall vascular health.
5.2. Practical ImplementationImplementing combined training programs in clinical and public health settings requires careful consideration of individual fitness levels, goals, and potential barriers to exercise. Strategies for improving adherence to combined training programs include personalized exercise prescriptions, support from healthcare providers, and the use of technology such as fitness trackers to monitor progress. To facilitate the adoption of combined training programs, it is essential to provide individuals with clear guidance on how to integrate these activities into their daily routines. This might include offering structured exercise programs through community centers or healthcare facilities, as well as providing online resources that allow individuals to customize their workouts based on their specific needs and preferences6, 7).
For individuals looking to perform both aerobic and anaerobic workouts in the same session, it is important to note that the order of exercises can influence training outcomes such as muscle hypertrophy42). Research suggests that performing resistance training before aerobic exercise may maximize muscle growth, while performing aerobic exercise first might impair strength gains. However, further studies are needed to examine how the order of exercise affects endothelial function, arterial stiffness, and other parameters related to atherosclerosis. Understanding these effects could help optimize combined training programs for cardiovascular health and disease prevention.
As research into the relationship between physical activity and cardiovascular health continues to evolve, several emerging trends and future directions warrant attention.
6.1. Wearable Technology and AccelerometersThe increasing use of wearable technology, such as fitness trackers and accelerometers, is revolutionizing the way physical activity is measured in research and clinical practice. These devices provide objective, continuous data on physical activity patterns, intensity, and duration, offering new insights into how physical activity contributes to cardiovascular health. A leading example of this is the electronic Framingham Heart Study (eFHS), which utilizes the Apple Watch to monitor habitual physical activity, heart rate, and sleep among its participants. This study has demonstrated that higher levels of physical activity, as measured by daily step counts from the Apple Watch, are associated with a lower predicted risk of CVD43). This pioneering approach illustrates how large cohort studies are now integrating the latest wearable devices to enhance the accuracy and scope of physical activity measurement.
Future research will likely focus on integrating data from wearable devices into personalized exercise prescriptions and monitoring the long-term effects of physical activity on atherosclerosis. Wearable technology also has the potential to enhance patient engagement in exercise programs by providing real-time feedback and personalized recommendations. As these devices become more sophisticated, they may be able to monitor physiological markers such as heart rate variability and blood glucose levels, offering a more comprehensive view of an individual’s cardiovascular health and response to physical activity.
6.2. Personalized Exercise MedicineThe concept of personalized exercise medicine is gaining traction as researchers seek to tailor exercise prescriptions based on individual genetic, metabolic, and lifestyle factors. This approach aims to maximize the cardiovascular benefits of physical activity while minimizing the risk of adverse effects. Personalized exercise medicine has the potential to improve adherence to exercise programs and enhance cardiovascular outcomes, particularly in populations at high risk for atherosclerosis.
Advances in multi-omics, including genomics, proteomics, and metabolomics, are paving the way for more precise exercise prescriptions. Multi-omics approaches allow for a comprehensive understanding of the molecular interactions underlying cardiovascular health and disease44, 45). For instance, genetic testing can identify predispositions to specific cardiovascular conditions, enabling the customization of exercise programs to target these risk factors46). Similarly, metabolomic profiling offers insights into an individual’s metabolic response to exercise, facilitating the fine-tuning of exercise intensity and duration to achieve optimal health outcomes46). Moreover, the gut microbiota’s influence on cardiovascular health suggests that personalized exercise programs might also consider dietary interventions to optimize outcomes46).
Furthermore, combining multi-omics data with wearable technologies and electronic health records can further personalize exercise prescriptions by providing continuous monitoring and real-time feedback, thereby optimizing health management and preventing adverse effects44). This integrative approach not only advances our understanding of how individual differences affect exercise responses but also underscores the potential of personalized exercise medicine to revolutionize cardiovascular health, particularly for those at heightened risk of atherosclerosis44).
6.3. Role of Other Exercise Modalities on Atherosclerosis DevelopmentIn addition to aerobic and anaerobic exercises, other modalities such as yoga, pilates, and tai chi are being explored for their potential cardiovascular benefits. These exercises often emphasize flexibility, balance, and stress reduction, which may complement the cardiovascular benefits of aerobic and resistance training. Research into the effects of these modalities on atherosclerosis and overall cardiovascular health is still in its early stages, but initial findings are promising. Yoga, for instance, has been shown to significantly improve endothelial function, which plays a critical role in cardiovascular health, particularly through the enhancement of FMD47). Similarly, tai chi has demonstrated benefits in reducing arterial stiffness and improving balance and cognitive function in older adults, which are important factors in cardiovascular health and atherosclerosis prevention47). These practices also promote mindfulness and relaxation, further enhancing their cardiovascular benefits. Future research should explore how these modalities can be integrated into broader exercise programs to provide a holistic approach to atherosclerosis prevention.
Fig.1 shows a summary of exercise benefits on cardiovascular system. The evidence supporting the role of physical activity in preventing atherosclerosis is robust and compelling. Regular exercise, whether in the form of aerobic exercise, resistance training, or a combination of both, offers significant protective effects against the development and progression of atherosclerosis. These benefits are mediated through a variety of mechanisms, including improvements in endothelial function, reductions in systemic inflammation, and favorable changes in lipid metabolism. Understanding the differential effects of various exercise modalities and the underlying mechanisms is crucial for optimizing exercise prescriptions and maximizing cardiovascular protection. As research continues to evolve, emerging trends such as wearable technology and personalized exercise medicine hold promise for enhancing the effectiveness of exercise interventions in preventing atherosclerosis.
Exercise benefits on cardiovascular system
YA received research funding from Tuning Folk Bio Japan.
