Atherosclerosis remains the most common underlying pathology of cardiovascular disease (CVD) and is the leading cause of death worldwide. Alongside peripheral artery disease, coronary heart disease and stroke, CVD accounts for approximately 32% of all global mortality.

For health and exercise professionals, this statistic underscores the critical role physical activity plays in both prevention and management. The evidence is unequivocal: regular exercise—particularly when it replaces a sedentary lifestyle—significantly reduces the risk of CVD-related mortality. Moreover, emerging research continues to affirm that the integration of aerobic training with resistance training produces additional cardiovascular benefits beyond either modality alone.

This article examines the pathophysiology and health consequences of atherosclerosis, highlights new findings on combined training strategies and presents evidence-based workouts you can adapt for clients to reduce cardiovascular disease risk and improve overall cardiometabolic health.

Understanding Atherosclerosis

Atherosclerosis is often described as a chronic disease where plaque builds up inside blood vessels, causing them to narrow and harden. “Athero” comes from the Greek word meaning “paste” or “gruel,” and refers to the fatty, gruel-like consistency of the plaque that forms on the inside of the arteries. This plaque is made up of low-density lipoproteins (i.e., the unhealthy cholesterol), fat particles, inflammatory cells (i.e., white blood cells that play a role in the body's response to injury or infection), smooth muscle cells and cellular debris (i.e., dead cells and cell waste products). As the plaque builds up over time in the arteries, the artery passageways get narrower, inhibiting the supply of oxygen and nutrients to parts of the body. "Sclerosis” refers to a “hardening.” Atherosclerosis formation is driven by a complex interaction of endothelial dysfunction (i.e., an impaired function of the inner lining of blood vessels), chronic inflammation (i.e., the body's immune system sends out specialized cells and substances that can become harmful to the body when constantly elevated), fat accumulation and arterial stiffness. A number of factors can worsen atherosclerotic plaque build-up such as high blood pressure, type 2 diabetes, excess body weight, tobacco use, physical inactivity, inadequate sleep, stress and excessive alcohol intake.

Health Consequences of Atherosclerotic Plaque Buildup

Atherosclerotic plaque buildup can occur in any arteries and veins of the body and can lead to several conditions, including blood clots, peripheral artery disease (PAD), angina or renal artery stenosis. Each of these are explained in detail below.

Blood Clots

Plaque buildup in blood vessels can lead to the formation of a blood clot, often referred to as a thrombus, which may seriously inhibit blood vessel function. A thrombus in an artery will negatively obstruct the delivery of blood, oxygen and nutrients to tissues, and potentially lead to a heart attack. A thrombus in veins can lead to a deep vein thrombosis, a serious condition where a blood clot forms in a deep vein (i.e., located deeper within the body, typically surrounded by muscle tissue), usually in the leg. The vein thrombus can lead to long-term complications with high blood pressure.

Peripheral Artery Disease

PAD occurs when plaque builds up in the arteries that supply blood to the arms and legs. With PAD, a person who is exercising can experience cramping, numbness and pain (collectively referred to as claudication) in the legs or arms due to insufficient blood and oxygen getting to the muscles. This condition can increase the risk of a heart attack. The pain and discomfort caused by claudication is usually relieved when exercise is stopped.

Angina

Plaque buildup in the arteries that supply the heart may result in angina, which is a type of chest pain or discomfort caused by reduced blood flow to the heart muscle. This reduced blood flow, referred to as ischemia, occurs when the heart muscle isn't receiving enough oxygen.

Renal Artery Stenosis

Plaque buildup that reduces blood supply to the kidney is known as renal artery stenosis (i.e., narrowing of a passageway). The kidneys need a good blood supply to function properly, including regulating blood pressure and filtering waste products. If the kidneys receive insufficient blood, this may trigger increased production of the hormone aldosterone, leading to salt and water retention and elevated blood pressure.

Exercise to the Rescue: The Protective Role of Physical Activity in Preventing Atherosclerosis

A wealth of landmark studies—including the Framingham Heart Study, the Nurses’ Health Study, the Atherosclerosis Risk in Communities Study, and the Women’s Health Initiative—consistently demonstrate a strong, long-term link between regular physical activity and improved cardiovascular health. Collectively, these findings show that exercise can slow the progression of atherosclerosis by enhancing endothelial function, reducing inflammation, improving blood lipid profiles and decreasing arterial stiffness.

From a physiological standpoint, one key benefit is the effect on endothelial function. Exercise stimulates the enzyme nitric oxide synthase in the vessel lining, which increases nitric oxide production. This molecule plays a vital role in vascular health by helping blood vessels relax and widen, thereby improving circulation, oxygen delivery and nutrient transport.

Exercise also exerts anti-inflammatory effects. Research indicates that physical activity promotes the release of specific anti-inflammatory cytokines—such as interleukin-6 and interleukin-10—which help suppress pro-inflammatory molecules. While acute inflammation is a normal, protective response to injury or harmful stimuli, chronic inflammation is a different story. When it lingers for months or even years, it can damage healthy cells and tissues, increasing the risk of cardiovascular disease and other chronic conditions.

Exercise Programming for Cardiovascular Benefits

There is plenty of established evidence that provides directions on the dosage of exercise needed to promote cardiovascular benefits. For example, one landmark study determined that people who engaged in 150 minutes weekly of moderate-intensity physical activity had a 14% lower coronary heart disease risk compared with those reporting no leisure-time physical activity. Additional findings by this research team indicated that those persons engaging in the equivalent of 300 minutes per week of moderate-intensity leisure-time physical activity had a 20% lower coronary heart disease risk compared with those reporting no leisure-time physical activity. Additionally, individuals who were physically active at levels below the minimum recommended amount had a significantly lower risk of coronary heart disease. In other words, some physical activity is better than none for promoting cardiovascular health.

Does Cardio + Resistance Training = Lower Risk of Atherosclerosis?

Recent research reinforces the value of combining cardiovascular exercise with resistance training as a strategy to maximize cardiovascular benefits while minimizing the limitations of either modality on its own. Studies consistently show that this integrated approach produces greater improvements in overall cardiovascular health than aerobic or resistance training alone and is particularly effective in reducing key CVD risk factors.

A practical framework for this approach includes 150 minutes of moderate-intensity aerobic exercise each week, paired with two to three resistance-training sessions targeting the body’s major muscle groups. This combination not only enhances cardiorespiratory fitness but also supports muscular fitness and metabolic health—creating a comprehensive foundation for long-term cardiovascular protection.

Practical Application: How to Design Evidence-based Exercise Programs to Improve Heart Health

Following are recently published international exercise program recommendations for both apparently healthy adults and adults with cardiovascular disease. In addition to specific recommendations for cardiovascular exercise and resistance training, sample workouts are provided for each type of training.  

As a reminder, encourage clients to do both aerobic exercise and resistance training for optimal cardiovascular benefits. To promote adherence, plan the workouts throughout the week in a way that best suits the client’s schedule. Also, be sure to individualize the program design and the progression of the program for each client’s health condition, fitness level, goals and barriers to exercise. For each workout, ensure the client performs an appropriate five- to 10-minute total-body warm-up and concludes each training session with an applicable three- to five-minute cooldown that includes post-workout stretching.

Aerobic Recommendations

• Perform 150–300 min of moderate-intensity exercise, or 75–150 min of vigorous-intensity exercise, or a combination thereof, weekly.

• Use ratings of perceived exertion (RPE) and/or the talk test to monitor intensity.

• Moderate intensity is RPE 12 to 13 (using the 6 to 20 scale); this equates to approximately 40 to 69% VO₂max.

• Vigorous intensity is RPE 14 to 16 (using the 6 to 20 scale); this equates to approximately 70 to 85% VO₂max.

• Suggested modalities include walking, jogging, swimming, elliptical trainer, rowing, stair climber, kickboxing, aquatic exercise and cardio-dance.

Sample Aerobic Workouts

Aerobic Workout #1: Maximal steady-state training (at moderate intensity; 12 to 13 on RPE scale)

Have the client select a modality of their choice and complete a 15-minute maximal steady-state training session. This is the level at which they can exercise continuously at a sustainable intensity. Progress their program by gradually increasing duration or intensity.

Aerobic Workout #2: High-intensity interval training (HIIT)

Have clients choose their preferred modality. In HIIT training, a bout consists of a work interval and a recovery interval. Table 1 demonstrates how the first bout might be designed. Begin with two bouts, which makes this a 14-minute HIIT workout (plus warm-up and cool-down). Additional bouts can be added based on the client’s goals and fitness level.

Table 1: Bout 1

Resistance-training Recommendations

• Muscle-strengthening activities at moderate or greater intensity that involve all the major muscle groups on two to three days of the week

• Perform eight to 10 dynamic or static resistance exercises, engaging all major muscle groups

• Complete one to three sets per exercise

• Exercise intensity should be between 50 to 80% of one-repetition maximum (1-RM) or eight to 15 repetitions to failure

Sample Resistance-training Workouts

Resistance-training Workout #1: Single-set training with emphasis on eccentric loading (eight exercises)

This workout can be performed using free weights or exercise machines, or a combination of both. Eccentric emphasis training is also known as negative training. This technique focuses on the lowering or lengthening phase of an exercise, where the muscle is under tension while lengthening.

Have the client lift the weight with a one- to two-second concentric contraction (shortening the muscle), then lower it slowly with control for three to five seconds. Complete eight to 15 repetitions to failure. Explain to the client that going to failure is the point where their muscles are unable to complete another repetition with proper form.

Here is a suggested routine and sequence:

• Chest press
• Squat
• Standing overhead press
• Alternating step-back lunges
• Biceps curls
• Seated rows
• Triceps extension
• Plank

Resistance-training Workout #2: Multi-set ladder training in circuit format (eight exercises)

Ladder resistance training involves performing multiple sets of an exercise by gradually increasing the intensity (on the ensuing sets), creating a “ladder” effect. This is a two-circuit ladder-training workout. When using a circuit format, have the client perform the first circuit with 13 to 15 repetitions of each exercise (not to failure) and the second circuit with eight to 10 repetitions of each exercise (to failure).

Here is a suggested routine for both circuits of this multi-set ladder-training session:

• Sumo squat
• Chest fly
• Alternating step-forward lunge
• Seated overhead press
• Reverse biceps curls
• Barbell rows
• Cable triceps pushdowns
• Crunches on a stability ball

Conclusion

Atherosclerosis remains one of the most significant global health burdens. However, it can be counteracted through strategic, evidence-informed exercise programming strategies to prevent and manage it. Through an individualized, evidence-based progressive lens, health and exercise professionals can empower clients to claim control of their cardiovascular future.

Oscar Chavez, Jr., BS, is a doctoral student in the exercise science program at the University of New Mexico in Albuquerque, where he serves as a graduate and research assistant in the Department of Health, Exercise and Sports Sciences. His research interests include the role of exercise in managing chronic conditions such as cardiovascular disease and diabetes, with a passion for bringing exercise as a lifestyle to all individuals.

Len Kravitz, PhD, CSCS, is the program coordinator of exercise science and a researcher at the University of New Mexico, where he recently received the Erna S. Fergusson Award for exceptional accomplishments. His research interests include energy metabolism, exercise product evaluation and exercise program measurement and assessment.