Proper programming of aerobic exercise is an integral part of any comprehensive fitness plan. Knowing when and how to incorporate different aerobic modalities will help fitness professionals guide their clients toward specific goals and health markers. In addition, knowing which adaptations aerobic training creates establishes a deeper understanding of the benefits of aerobic conditioning on a physiological level.

The minimum guidelines for aerobic exercise, created by the American College of Sports Medicine in 2007, and re-affirmed by the Department of Health and Human services in 2018, are as follows:

1. 150—300 minutes of moderate-intensity physical activity 

or 

2. 75—150 minutes of vigorous-intensity physical activity per week.

While these are the minimum recommended aerobic exercise total duration each week, more aerobic activity provides greater proportional benefit.

Most clients will benefit from a combination of aerobic and resistance training. This is referred to as concurrent training and requires specific programming considerations. The most critical factor for concurrent training is fatigue management, as overall training volume is high and clients may not be able to sustain the program for prolonged mesocycles.  

Therefore, performing aerobic exercise and strength training in the same session is not advisable for beginner or intermediate clients. 

Older research has concluded that aerobic exercise has an inhibitory effect on muscular strength and hypertrophy adaptations.² However, newer research calls this into question. 

Recent research concludes that the interference effect is nullified if cardio and strength workouts are not performed in the same session when training volume is equated. Thus, a key programming question is how to integrate both aerobic and strength training without sacrificing the training volume or quality of either.

Acute responses to aerobic exercise can be divided by system: cardiovascular, respiratory, endocrine, and metabolic responses. The extent and duration of these responses are linearly related to exercise intensity. 

In laboratory conditions, aerobic exercise intensity is quantified as a percentage of V̇O₂ max. V̇O₂ max is defined as the maximum volume of oxygen that can be consumed (utilized by the tissues) per minute. Another commonly used measurement of intensity is heart rate [HR]. 

Cardiovascular Responses

The cardiovascular system (heart and vessels) responds to exercise by increasing the delivery of oxygen to working muscles in order to maintain exercise performance. This includes vasodilation of the blood vessels and an increase in the work capacity of the heart muscle.  

At rest, the sympathetic and parasympathetic nervous systems create a balance between stimulation and inhibition of the heart respectively. As exercise intensity increases, the sympathetic nervous system increases stimulation, while the parasympathetic system decreases inhibition. The result is an increase in heart rate and stroke volume.  

Stroke volume describes the amount of blood ejected from the left ventricle per heartbeat. The product of HR x SV is referred to as cardiac output [CO, Q̇]. Heart rate is measured in beats per minute, and stroke volume is measured in liters per beat; therefore, the units of Q̇ are liters per minute. 

Stroke volume increases as a result of greater stimulation from the sympathetic nervous system during exercise. However, there is also a mechanical stimulus responsible for the increase in SV. The increase in SV results in an increase in the amount of blood which returns to the heart via the veins: this is referred to as venous return.

The Frank-Starling Mechanism

The increased venous return during exercise results in the expansion of the cardiac muscle tissue. This results in stored elastic potential energy within the tissue. During heart muscle contraction, elastic energy is released which increases the amount of blood ejected from the ventricles.

This increased blood volume ejection due to the increased elastic energy in the heart is known as the Frank-Starling mechanism and assists the body during exercise in providing sufficient oxygen.

Thus far has been a discussion about changes specifically in the heart during aerobic exercise, but changes also occur in the vessels themselves. At the onset of exercise, a vasodilator, nitric oxide, secretes within the vessel walls, increasing their inner diameter. This increase in inner diameter reduces the resistance to blood flow; resistance to flow is referred to as total peripheral resistance [TPR], and also contributes to the overall increase in stroke volume. At the same time, skeletal muscle contracts around veins; this constricts them, increasing venous pressure. This increase in venous pressure aids in venous return.

Finally, active respiration (heavy breathing during exercise) increases venous return by creating a pressure gradient between the thorax and the abdomen, referred to as the respiratory pump. During exercise, blood flow redirects away from the core of the body, towards skeletal muscle to aid in exercise performance.

Blood pressure [BP] (measured in mmHg) is the force blood exerts on vessel walls; it is measured as the ratio of force during contraction (systole) versus relaxation (diastole).  During aerobic exercise, systolic BP increases linearly with exercise intensity. However, in a healthy heart, diastolic BP changes very little.

As a result, the mean arterial pressure [MAP] increases linearly with exercise intensity. MAP cannot be calculated as the simple arithmetic average of systole and diastole because the heart spends more time in diastole than systole. Therefore, the following formula is used:

MAP = DBP + [.333 x (SBP – DBP)]

A metric of the oxygen demand placed on the heart is the rate pressure product [RPP] and can be expressed as the product of HR x SBP. 

Key Formulas

Q̇ = HR x SV

MAP = DBP + [.333 x (SBP – DBP)]

RPP = HR x SBP

Respiratory Responses

Respiratory responses to exercise include an increase in breathing rate and depth and are mostly linear in nature. As exercise reaches maximal levels, respiratory rate increases exponentially to help buffer body pH in response to an increasing amount of lactate in the cells and bloodstream. At rest, the volume of air inhaled and exhaled naturally is referred to as tidal volume, with the average breathing rate at rest approximately 12 breaths per minute. Breathing frequency reaches as high as 45 breaths per minute as exercise reaches maximal levels, with breathing depth increasing steadily until it plateaus at about 70 percent V̇O₂ max.⁹ 

The Respiratory Exchange Ratio [RER or RQ] describes the ratio of carbon dioxide exhaled to the volume of oxygen consumed. Metabolic gas analyzers measure the RER at the mouth in laboratory settings. The ratio is expressed via the following formula:

RER = VCO2/VO2

The RER is an estimate of fuel utilization at rest and during exercise. At rest, a non-fasted person with a normal (non-ketogenic) diet has an average RER of .82, which means that 60 percent of their total energy production derives from fat, while the remaining 40 percent derives from carbohydrates.⁷ As exercise intensity increases the preferred energy source shifts from fat to carbohydrates.

It is important to note that RER values above 1.0 are routinely observed in laboratory testing. This is due to the fact that RER is measured at the mouth and is therefore affected by breathing rate. At a certain exercise intensity, ventilation increases exponentially, not linearly with exercise intensity, this is referred to as the ventilatory threshold (VT).

This does not occur due to oxygen demand. Rather the high breathing rate is necessary to maintain pH when high levels of lactate are being produced. As a result, RER levels at maximum exercise are often observed to be 1.1 or higher.

Metabolic Responses

During aerobic exercise, the body supplies ATP to working muscles through both aerobic and anaerobic means, with anaerobic means supplying the majority of ATP at higher intensities. Thus, the higher the exercise intensity, the greater reliance on anaerobic sources of ATP (phosphocreatine and glycolysis).

However, these sources are finite, meaning that high intensity exercise can only be maintained for a relatively short period of time. Ultimately, the onset of fatigue is, at least in part, due to the availability of carbohydrates and fats for oxidation in working muscles to produce sufficient ATP.

Endocrine Responses

During exercise the endocrine system facilitates fuel availability and uptake by muscle cells. The hormones of interest include the following: epinephrine, norepinephrine, glucagon, insulin, cortisol, and growth hormone.

Glucagon and Insulin

The pancreas produces and circulates glucagon and insulin. Glucagon and insulin are regulatory hormones that control blood glucose levels by moving glucose molecules in and out of cells. Specifically, insulin lowers blood glucose levels by binding to glucose molecules and transporting them across cell membranes via specialized channels called GLUT4 transporters. In essence, insulin lowers blood glucose and increases glucose availability in cells for glycolysis.

Glucagon does precisely the opposite, it increases blood glucose levels by moving glucose molecules out of cells and into the bloodstream. Glucagon also stimulates the breakdown of glycogen (the stored form of glucose) into glucose. 

During exercise, blood concentrations of insulin decrease, and other mechanisms which move glucose into cells increase. Furthermore, glucagon levels increase, improving insulin sensitivity. The combination of the two also leads to an increase in fat breakdown (lipolysis), resulting in more fatty acids available for fuel.

Cortisol and Growth Hormone 

The adrenal cortex releases cortisol, a hormone with wide-ranging effects. In the context of exercise, cortisol primarily stimulates the conversion of amino acids into fuel sources and intermediates for aerobic exercise.

Cortisol encourages the breakdown of muscle proteins in order to facilitate the conversion of some amino acids into glucose or intermediates for the Krebs cycle. Cortisol concentrations are directly related to exercise intensity, with higher intensity correlating to higher cortisol levels in the blood.³ Growth hormone is secreted from the anterior pituitary gland and increases cortisol and glucagon levels in the blood.

Epinephrine and Norepinephrine 

Lastly, epinephrine and norepinephrine (collectively referred to as the catecholamines) are stimulatory and inhibitory endocrine responses respectively; they are colloquially referred to as the “fight or flight” hormones. The adrenal medulla releases these hormones when the body perceives stress, such as in physical exercise. They increase heart rate and blood pressure, delivering more oxygenated blood to working muscles in order to maintain exercise performance. 

In summary, exercise leads to increases in glucagon, cortisol, growth hormone, epinephrine, and norepinephrine concentrations. Plasma concentrations of these hormones directly correlate to exercise intensity. Their collective effects facilitate the availability of oxygen and other nutrients necessary for the production of the ATP.

Long-term adaptations to aerobic exercise can be divided into the following categories: cardiovascular, respiratory, musculoskeletal, metabolic, and endocrine. This section reviews each of these systems as well as examines the effects on body composition and exercise performance. Understanding these effects aids the personal trainer as they set long-term goals with their clients, as well as guide programmatic decisions at the mesocycle and macrocycle level. 

Cardiovascular Adaptations

Maximal aerobic power is expressed by the Fick Equation:

V̇O₂ (L/min) = Q̇ x a- O₂ difference.

As previously mentioned, cardiac output [Q̇] is the product of stroke volume and heart rate, and measures the amount of blood, in liters, pumped into systemic circulation per minute. The a- O₂ difference is the difference in oxygen concentration in arterial versus venous blood, thus it measures how much oxygen the cells extract from the blood. The Fick equation represents both oxygen delivery (Q̇) and oxygen extraction (a- O₂ difference). Chronic adaptations to aerobic exercise occur in both oxygen delivery and extraction.

The primary adaptations in cardiac output occur via increases in stroke volume. Long-term cardiovascular exercise results in hypertrophy of the cardiac muscle cells, specifically in the left ventricle. Another notable chronic adaptation is an enhanced sensitivity to insulin.

This results in a larger left ventricle cavity and a stronger contractile function of the ventricle walls. Meanwhile, filling time (the period of time in which the bicuspid and tricuspid valves are open) increases. An increase in blood volume also results from chronic cardiovascular training.¹¹ These factors combine to increase stroke volume.

Maximal heart rate is largely genetic and age dependent and cannot be changed via exercise. However, at resting and submaximal exercise, a reduction in heart rate is observed. Three mechanisms explain this phenomenon:

• Increase in parasympathetic stimulation
• Decrease in sympathetic stimulation
• Lower intrinsic heart rate⁴ 

The effect of long-term aerobic exercise on blood pressure varies based upon resting BP and overall health of the client. For individuals with normal blood pressure, average changes are very small. On the other hand, in individuals with hypertension (SBP> 140 OR DBP > 90 mmHg) scientists have observed more substantial reductions.⁸  

Furthermore, the reductions in blood pressure following a bout of aerobic exercise have been observed and are termed “postexercise hypotension.”  Finally, as the left ventricle hypertrophies, SBP decreases for a given submaximal workload. This demonstrates an improved aerobic capacity in response to long-term term training. 

Respiratory Adaptations

Respiratory adaptations to long-term aerobic exercise are less robust than the adaptations observed in other systems. However, a few changes at both sub-maximal and maximal work rates occur in minute ventilation, and ventilatory efficiency. 

Minute ventilation (V̇_E) decreases at submaximal work rates by a significant amount.⁴ However, V̇_E increases at maximal work rates. This is because at submaximal work rates tidal volumes increase but breathing frequency either stays the same or slightly decreases. In maximal work rates both frequency and tidal volume increase.

Another adaptation to long-term aerobic training is hypertrophy of the diaphragm and other muscles used during active breathing. This results in a decreased oxygen cost of ventilation, thus an increase in efficiency. This efficiency frees up more oxygen for use in other muscles while still meeting the oxygen needs of the muscles used in active breathing.

Musculoskeletal Adaptations

Aerobic activity stimulates type I muscle fibers with little to no effect on type IIa or IIx fibers.¹¹ Research evidence suggests that some mild shifting in fiber type may occur, resulting in a shift away from IIx and IIa towards type I fiber types.

However, the extent to which this occurs, and the duration of training needed to stimulate it remain unclear.¹⁰ This potential shift would result in a decrease in the maximum velocity of shortening and peak force production of a muscle fiber along with an increase in fiber efficiency, aerobic capacity and fatigue resistance.

Bone and Connective Tissue Adaptations

Bone mineral density [BMD] describes the amount of bone mineral content per unit volume of bone tissue. BMD is the standard measurement of bone strength; it rises through childhood and early adulthood, plateaus in middle age, and declines later in life.

Resistance training exercises, specifically activities which load the hips and axial skeleton, have been shown to be the most effective.⁵ However, aerobic activities, such as running, have also been shown to improve BMD.⁵ Lower impact activities such as walking, aquatics, and upper body cycling have not been found to be beneficial for bone adaptation.

Metabolic Adaptations

Within type I muscle fibers, numerous adaptations occur that enhance the fiber’s capacity to produce ATP aerobically. Capillary density, defined as the number of capillaries surrounding one muscle fiber, increases substantially over a period of a few weeks to two months. This increases oxygen supply and the rate of waste removal.

There is also an increase in the concentration of cellular myoglobin, a molecule that transports oxygen from the cell wall to the mitochondria. Other enzymes and molecular transporters increase in intracellular concentration as well. Mitochondrial density also increases, albeit more slowly than myoglobin concentrations or capillary density. 

In addition to oxidative capacity, type I muscle fibers also increase glycogen storage. Glycogen, the stored form of glucose, produces ATP via the anaerobic pathway, through glycolysis. Glycolysis provides a fast means of producing ATP and is used by cells in conjunction with aerobic metabolism to meet ATP demands. 

In summary, long-term aerobic exercise training results in increased capillary density, myoglobin, oxidative enzymes, and mitochondrial density. The collective effect improves the fiber’s ability to utilize oxygen to produce ATP.

Direct measurement of aerobic power output (V̇O₂) is not practical outside of laboratory conditions. However, heart rate correlates strongly to V̇O₂ and is easily measured manually or with optical or electrical monitors. Maximal heart rate directly relates to age and can be calculated through various equations, the simplest of which is the age-predicted maximal heart rate formula:

APMHR = 220 – AGE

This equation has been shown to be accurate within approximately 10 – 15 beats.¹¹ 

A more accurate measurement is the Karvonen formula or heart rate reserve method (HRR), which incorporates resting heart rate (RHR) instead of using age-predicted max heart rate. The Karvonen formula is:

HRR = APMHR – RHR

Target HR (THR) = (HRR x exercise intensity) + RHR

To accurately measure resting heart rate, clients must measure their heart rate early in the morning, typically immediately after waking up naturally, prior to the ingestion of any stimulants such as caffeine. 

Subjective measurements of aerobic exercise intensity are also available, such as the talk test, or the rate of perceived exertion (RPE). The talk test measures intensity based upon the ease with which the client can carry a conversation during aerobic exercise.

If a client is able to carry a full conversation with no difficulty, intensity is likely low. On the other hand, if they are unable to speak at all, intensity is high, bordering on maximal. The RPE scale was originally a 6 – 20 scale which correlated to heart rate during aerobic exercise. A more common RPE scale is the modified 0—10 scale. In either case, clients subjectively report their level of exertion, which can be correlated to low, medium, or high intensity.

As with all exercise programs, the principles of specificity, overload, and periodization apply. The principle of specificity states that the body will adapt to the stimulus to which it is exposed, meaning that in order to trigger adaptations in specific muscle groups and systems, they must be targeted during training.

The principle of overload states that these muscle groups and systems must be exposed to a greater level of exertion than normal in order for them to adapt. This can be in the form of greater intensity, and/or greater duration of the stimulus.

Lastly, the principle of periodization states that overload can only be maintained through specific, measured, and gradual increases in stimulus over time. Furthermore, periodization also states that the body must experience periodic reductions in stimulus in order to re-sensitize the adaptive pathways and allow for sufficient recovery from training. 

The basic variables of exercise program design are: frequency, intensity, and duration. Frequency refers to the number of aerobic sessions per week. Intensity is a measurement of how hard a training session is, as mentioned it is measured either objectively (APMHR, HRR, etc..) or subjectively (talk test, RPE). Duration refers to the minutes of actual training, warm-ups and cool-downs are not included.

The number of aerobic training sessions per week will depend upon client training status and fatigue management. The minimum recommended guidelines for aerobic exercise are 150—300 minutes of moderate intensity exercise per week or 75—150 minutes of vigorous activity per week.

Beginner clients will focus more on moderate intensity sessions spread evenly throughout the week. As clients progress, vigorous sessions can be added, replacing moderate sessions. If clients manage their fatigue well via proper sleep and nutrition, weekly progressions are expected.

Training zones vary based upon the calculations used to gather intensity data. Using a percentage of APMHR from between 64 percent to 95 percent will provide an appropriate stimulus to improve aerobic fitness. If HRR is used, a smaller range, 40 percent to 89 percent should be used. When creating an aerobic training protocol for clients, calculate a target heart rate range by using either formula twice, a low end, and a high end. Consider the example below, using the HRR formula. 

A.J. is a 42 year old male. His resting heart rate is 80 bpm. If his training zone is between 40 percent and 89 percent of HRR then his training zone is calculated in the following steps:

APMHR = 220 – 42  = 178 bpm

HRR = 178 – 80  = 98 bpm

THR_{low end} = (98 x .4) + 80 = 119.2 bpm

THR_{high end} = (98 x .89) + 80 = 167.22 bpm

Based on the above, A.J. should have a target heart rate between 119 and 167 beats per minute, rounded to the nearest digit.

Intensity of training: optimal training zones based on RPE

Most clients will have little familiarity with subjective exercise scales, as a result their initial RPE reports will be quite inaccurate. This is further complicated by the fact that many novice exercisers have not experienced true maximal or near maximal level exercise, so they cannot accurately say what a “10 out of 10” feels like. However, research in the last five years has shown that repeated use of the RPE scale during the same exercise modality improves its reliability and validity.⁶ Combining RPE and HR measurements will accelerate this process.

Heart Rate Zones

Heart Rate Zones are another method of assigning aerobic intensity. They correspond to ranges of heart rate as a percentage of maximal heart rate. Assigning intensity based on heart rate zones can be a useful way to map out the right workout intensity for a given workout.

Zone 1: Recovery or Warm-up (50-60% HRmax)

This zone represents low-intensity exercise, typically used for warm-ups, cool-downs, and recovery sessions.

Zone 2: Aerobic or Base Training (60-70% HRmax)

This zone corresponds to moderate-intensity exercise, where the body primarily uses aerobic energy systems. Training in this zone can improve endurance and cardiovascular efficiency.

Zone 3: Tempo or Threshold Training (70-80% HRmax)

This zone represents a transition between aerobic and anaerobic energy systems. Training in this zone can improve lactate threshold, increase aerobic capacity, and enhance overall fitness.

Zone 4: Sub-maximal or Anaerobic (80-90% HRmax)

This zone corresponds to high-intensity exercise, where the body relies more on anaerobic energy systems. Training in this zone can improve speed, power, and muscular strength.

Zone 5: Maximal or Redline (90-100% MHR)

This zone represents maximal or near-maximal effort. Clients will be unable to maintain this intensity for more than several seconds. Training in this zone can improve neuromuscular coordination, speed, and power.

The last two decades have seen a boon in wearable exercise technology including accelerometers, pedometers, electrical and optical heart rate monitors, and GPS units. The wealth of options has driven the cost down, making devices practical and affordable for the average consumer.

Accelerometers and pedometers measure activity via a pendulum which swings in time with each stride, completing an electrical circuit and allowing a microchip to track. They are highly effective at measuring steps, but less accurate at quantifying other forms of physical activity. Electrical heart rate monitors measure heart rate via a chest strap, which detects electrical activity in the heart and then calculates heart beats per minute.

Optical heart rate monitors measure heart rate via infrared measurement of blood vessel perfusion. These are typically worn on the wrist via smartwatch. They have been shown to be very accurate for steady state exercise, with a higher error rate during interval exercise. Lastly, GPS trackers connect to a network of satellites and triangulate position, direction, speed and other kinematic variables. 

Wearable technology, such as those mentioned above, can provide trainers a wealth of quantitative data regarding clients’ performance, both during sessions and beyond. Quite a few wearables even track recovery variables such as resting heart rate, sleep quantity and quality. They can also be used to estimate basal metabolism and therefore provide info for dietary programming. Given their usefulness they are fastly becoming an essential part of every trainer’s toolkit, although there is room for error, so consider that when using these devices 

Aerobic training creates many short and long-term changes in the body.

On an acute basis, the heart increases vasodilation of the blood vessels and an increase in work capacity, resulting in greater heart rate and stroke volume. Systolic blood pressure goes up along with respiratory rate, ATP production, epinephrine, norepinephrine, glucagon, cortisol, and growth hormone, while insulin decreases.

Chronic cardiovascular exercise results in hypertrophy of the cardiac muscle cells, improved aerobic capacity, an increase in oxygen efficiency, stimulation of type I muscle fibers, some small strength changes in bone adaptation, increased capillary density, myoglobin, oxidative enzymes, and mitochondrial density.

When perscribing cardiovascular exercise programs, fitness professionals should be aware of general exercise principles and be able to set and track target heart rate intensities using the modern technology available to them.

1. Haskell, W. L., Lee, I. M., Pate, R. R., Powell, K. E., Blair, S. N., Franklin, B. A., Macera, C. A., Heath, G. W., Thompson, P. D., & Bauman, A. (2007). Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Medicine and science in sports and exercise, 39(8), 1423–1434. https://doi.org/10.1249/mss.0b013e3180616b27

2. Hickson RC. Interference of strength development by simultaneously training for strength and endurance. Eur J Appl Physiol Occup Physiol. 1980;45(2–3):255–63

3. Jacks, D., Sowash, J., Anning, J, McGloughlin, T, & Andres, F. Effect of exercise at three exercise intensities on salivary cortisol. J Strength Condit Res 16(2):286-289, 2002.

4. Kenney, W., Wilmore J, & Costill, D. Physiology of Sport and Exercise. 7th ed. Champaign, IL: Human Kinetics, 2020.

5. Kohrt, W., Bloomfield, S., Little, K., Nelson, M., & Yingling V.  American College of Sports Medicine position stand: Physical activity and bone health. Medicine and Science in  Sports and Exercise 36(11):1985-1996, 2004.

6. Lea, J., O’Driscoll, J. M., Hulbert, S., Scales, J., & Wiles, J. D. (2022). Convergent Validity of Ratings of Perceived Exertion During Resistance Exercise in Healthy Participants: A Systematic Review and Meta-Analysis. Sports medicine – open, 8(1), 2. https://doi.org/10.1186/s40798-021-00386-8

7. McArdle, W., Katch, F., & Katch, V.  Exercise Physiology: Nutrition, Energy, and Human Performance. (7th ed.) Philadelphia: Lippincott Williams & Wilkins

8. Pescatello, L., Franklin, B., Fagard, R., Farquhar, W., Kelley, G., & Ray, C. American College of Sports Medicine position stand. Exercise and hypertension. Medicine and Science in Sports and Exercise 36(3):533-553, 2004.

9. Power, S., Howley, E., & Quindry, J. (2021). Exercise Physiology: Theory and Application to Fitness and Performance (11^th). McGraw Hill LLC

10. Rico-Sanz, J., Rankinen, T., Joanisse, D., Leon, A., Skinner, J., Wilmore, J., Rao, D., & Bouchard, C. Familial resemblance for muscle phenotypes in the HERITAGE Family Study. Med Science in Sports and Exercise 35(8):1360-1366, 2003.

11. Schoenfeld, B. J. & Snarr, R. (2021). NSCA’s Essentials of Personal Training (3^rd) Human Kinetics, Champaign, IL. 

12. Schumann, M., Feuerbacher, J. F., Sünkeler, M., Freitag, N., Rønnestad, B. R., Doma, K., & Lundberg, T. R. (2022). Compatibility of Concurrent Aerobic and Strength Training for Skeletal Muscle Size and Function: An Updated Systematic Review and Meta-Analysis. Sports medicine (Auckland, N.Z.), 52(3), 601–612. https://doi.org/10.1007/s40279-021-01587-7

13. U.S. Department of Health and Human Services. Physical Activity Guidelines Advisory Committee Scientific Report. Washington, DC: U.S. Department of Health and Human Services, 2018.