EHR522 Exercise for Metabolic & Renal Conditions Week 3 - Hyperlipidaemia and Dyslipidaemia PDF

EHR522 EXERCISE FOR METABOLIC & RENAL CONDITIONS WEEK 3 – HYPERLIPIDAEMIA AND DYSLIPIDAEMIA HYPERLIPIDAEMIA AND DYSLIPIDAEMIA • Lipids – Refers to a variety of fats that are necessary for normal body functioning • However, abnormal lipid levels, particularly of cholesterol and triglyceride, are m...

EHR522 EXERCISE FOR METABOLIC & RENAL CONDITIONS WEEK 3 – HYPERLIPIDAEMIA AND DYSLIPIDAEMIA HYPERLIPIDAEMIA AND DYSLIPIDAEMIA • Lipids – Refers to a variety of fats that are necessary for normal body functioning • However, abnormal lipid levels, particularly of cholesterol and triglyceride, are modifiable CVD risk factors • Dyslipidaemic patients have an elevated risk of CVD. Therefore, when delivering exercise testing and training, you need to be conscious of possible CVD signs and symptoms 2 HYPERLIPIDAEMIA AND DYSLIPIDAEMIA • Hyperlipidaemia and dyslipidaemia are terms that are frequently used interchangeably to describe abnormal blood lipid profiles • Hyperlipidaemia – A general term used to refer to chronic elevations in the fasting blood concentrations of triglyceride, cholesterol, or specific sub-fractions of each • Dyslipidaemia – A combination of genetic, environmental and pathological factors that can work together to abnormally alter blood lipid and lipoprotein concentrations • Dyslipoproteinaemia – Refers broadly to elevated lipoprotein concentrations 3 HYPERLIPIDAEMIA AND DYSLIPIDAEMIA • Most severe forms of dyslipidaemia and dyslipoproteinaemia are linked to genetic defects in cholesterol or triglyceride metabolism • Secondary dyslipidaemia usually results from metabolic dysfunction that arises from the accumulation of ectopic fat, insulin resistance, diabetes mellitus, hypothyroidism and renal insufficiency and nephrotic kidney disease • Diet and nutrient composition, body weight management, physical activity, and exercise programming are featured in the latest guidelines as important interventions for blood lipid and lipoprotein control 4 HYPERLIPIDAEMIA AND DYSLIPIDAEMIA Lipids serve a variety of crucial physiological roles, including • Energy storage • Body insulation • Maintenance of bile acids • Steroid hormone production • Structure of cell membranes • Metabolic regulation 5 HYPERLIPIDAEMIA AND DYSLIPIDAEMIA • A wealth of data supports the relationship between dyslipidaemias and greater risk for CVD • Arterial atherosclerotic lesions, characterised first by fatty acid streaks and later by fibrous plaque, begin in childhood and increase in prevalence and size with age • Development of these lesions, leading to CAD and cardiovascular complications, is significantly related to concentrations of total blood cholesterol, low-density lipoprotein cholesterol (LDLc), and triglycerides and inversely with levels of high-density lipoprotein cholesterol (HDLc) 6 HYPERLIPIDAEMIA AND DYSLIPIDAEMIA • Relationships between blood lipid concentrations and CVD appear to be consistent in men and women and in those with and without documented CVD • The association between triglyceride concentrations and the incidence of CVD is a topic of ongoing debate • Race, gender, genetics, disease states and physical characteristics, among other factors, will influence the strength of association between blood lipids and lipoproteins, the atherosclerotic process and CVD outcomes 7 HYPERLIPIDAEMIA AND DYSLIPIDAEMIA - MEDICATION • Just over half of US adults needing cholesterol medication are actually taking it • LDLc and non-HDLc are the primary targets for lipid- lowering interventions • Statins are by far the most frequently prescribed lipid-lowering agents • Approximately two-thirds of apparently healthy adults at high risk for CAD are not taking needed medications for dyslipidaemia 8 LIPOPROTEIN METABOLIC PATHWAYS • Atherosclerotic disease processes originate in early childhood and continue to develop through the interactions of genes, modifiable and non-modifiable environmental exposures • Blood lipoproteins provide a system of transportation for the movement of lipids between the intestine, liver and extrahepatic tissue Important enzymes and transfer proteins facilitate these interactions • Lipoprotein lipase (LPL) • Hepatic lipase (HL) • Lecithin-cholesterol acyltransferase (LCAT) • Cholesterol ester transfer protein (CETP) 9 LIPOPROTEIN METABOLIC PATHWAYS • The LDL receptor pathway consists of a sequence of chemical steps designed for the delivery of lipids to extrahepatic tissue • A second pathway, reverse cholesterol transport, involves a sequence of chemical reactions necessary for returning lipids from peripheral tissue to the liver for metabolism and excretion 10 LDL RECEPTOR PATHWAY • Low-density lipoprotein particles are the primary cholesterol carriers and deliver LDLc to extrahepatic tissue where LDL receptors located on the cell’s surface mediate its uptakes • Once the LDLc is recognised by the receptor, LDL is moved inside the cell and used for cellular metabolic needs • This process also initiates within the cell a negative feedback response, causing a reduction in cellular cholesterol synthesis while promoting cholesterol storage • As these processes occur, cellular LDL receptor synthesis is suppressed and further cellular LDL uptake is halted 11 REVERSE CHOLESTEROL TRANSPORT • Cholesterol is moved to the liver for catabolism by a process termed reverse cholesterol transport • This elimination of cholesterol from the peripheral tissue involves several processes, the most notable of which involves a pathway using nascent HDL particles secreted by the liver 12 POSTPRANDIAL LIPAEMIA • Generally, the time needed after a meal for blood triglyceride levels to return to fasting levels is 6 – 8 hours • Exaggerated or prolonged lipaemia is associated with increased CAD risk • Elevated postprandial lipaemia (PPL) may initiate many harmful events associated with endothelial dysfunction and arterial plaque build-up • Prolonged PPL also promotes inflammation, oxidative stress, and thrombosis or blood clot formation • Genetic factors affect the magnitude of the postprandial responses, but postprandial lipid responses are also affected by exercise and nutrient composition 13 METABOLIC DYSLIPIDAEMIA – TRIGLYCERIDAEMIC DYSLIPIDAEMIA • Elevation of bloodborne fatty acids observed with metabolic dyslipidaemia affects the vascular endothelium by reducing nitric oxide production, inducing adhesion characteristics, facilitating oxidative damage and inflammation, and resulting in diminished vascular compliance and reactivity 14 CLINICAL CONSIDERATIONS • The most recent guidelines differ in recognising traditional cut-points for managing blood lipids and pharmacological treatment • Abnormal cholesterol levels are defined as follows: − Total cholesterol ≥ 5.5 mmol/L − HDLc < 1.0 mmol/L (men) or < 1.3 mmol/L (women) − LDLc ≥ 3.5 mmol/L 15 CLINICAL CONSIDERATIONS 16 CLINICAL CONSIDERATIONS Given that most physical manifestations of dyslipidaemic diseases are absent, these conditions are considered silent diseases. Hypercholesterolaemia − All forms of hypercholesterolaemia increase the risk for premature atherosclerotic disease; however, familial hypercholesterolaemia carries the highest risk Hypertriglyceridaemia − In addition to familial combined hypercholesterolaemia, there are other genetic conditions that can result in elevated triglycerides 17 PHYSICAL EXAMINATION AND DIAGNOSTIC TESTING • Clinical screening for dyslipidaemia includes analysis of the blood lipid profile measured every 5 years and can begin at age 20 • Although guidelines do not recognise hypertriglyceridaemia as a primary target of lipid lowering, exaggerated triglycerides can prohibit an accurate assessment of the primary lipid target (LDLc), contribute to vascular endothelial dysfunction and increase CHD risk 18 EXERCISE TESTING • Exercise testing should follow protocols used in populations at risk for CAD, with the possibility of dyslipidaemic patients having latent CVD being higher than in the healthy population • Exercise is not contraindicated for those with a dyslipidaemic blood profile. Rather, attention is given to possible existing comorbidities • When diseases are suspected or present, the protocols for testing a patient are likely to change • You must be cognisant and observant of signs and symptoms that may suggest underlying CVD while testing patients with dyslipidaemia 19 CARDIOVASCULAR TESTING • The purpose of cardiovascular testing in an individual with dyslipidaemia is to − Help diagnose CAD − Determine the functional capacity of the individual − Help determine an appropriate exercise intensity range • If a patient with dyslipidaemia is otherwise healthy, the anticipated responses to an exercise test are no different from what is expected in healthy individuals 20 CARDIOVASCULAR TESTING • Prescribed medications can alter anticipated exercise responses − In some cases, lipid-lowering medications such as statins and fibric acid, when used individually, or in combination, have the potential to cause muscle damage, releasing proteins such as myoglobin into the blood (eg. rhabdomyolysis) and reducing exercise performance − These proteins are also harmful to the kidneys. Elevated levels may lead to kidney failure and, in extreme cases, death − Also, chronically high cholesterol levels can result in the formation of tendon xanthomas. Individuals with this condition may experience biomechanical problems that contribute to reduced exercise performance 21 MUSCULOSKELETAL TESTING • Most often, 1RM tests can be used. However, if comorbidities are present, other tests may be employed • Other less hazardous tests include the estimation of 1RM • Special attention should always be given to any possible orthopaedic issues the patient may have 22 FLEXIBILITY TESTING • Patients with dyslipidaemia can perform testing protocols for the healthy population 23 TREATMENT • The primary goal in the clinical management of dyslipidaemias is to reduce the global risk for CVD • Attention focuses on reducing the severity and number of traditional CVD risk factors • The fundamental interventions for those with dyslipidaemia are to engage in regularly practiced physical activity, consume a heart-healthy diet, lose weight and prevent weight regain after weight loss. All characteristics of secondary dyslipidaemia are mitigated when these lifestyle behaviours are consistently practiced • In addition, efforts should be made to quit smoking, improve stress management and practice individually appropriate behavioural techniques for long-term adherence to healthy lifestyle changes 24 DIET • Adopting a healthy diet is crucial for treating dyslipidaemia and managing healthy blood lipid concentrations • A Mediterranean-style diet is consistent with current recommendations • The benefits of a Mediterranean-style diet are due, in part, to the fact that it is low in saturated fats, trans fats, cholesterol, sodium, red meat, simple sugars and refined grains • In addition, the Mediterranean diet provides nutrients such as omega-3 fatty acids, polyunsaturated fatty acids, soluble fibre and carotenoids, all of which are associated with cardiometabolic health 25 DIET • The health benefits of moderate alcohol consumption, such as an increase in HDLc and enhanced vascular endothelial function, appear to be unrelated to the type of alcoholic beverage consumed. Therefore, patients who are responsible drinkers may be encouraged to continue moderate alcohol use 26 DIET • Diets with fat intake exceeding 35% are likely to include too much saturated fat, contributing to elevated LDLc, insulin resistance and weight gain • Low-fat, high-carbohydrate diets promote features of atherogenic dyslipidaemia, such as elevated triglycerides and lower HDLc • Functional Foods – Contain biologically active substances that impart medicinal or health benefits beyond their basic nutritional components • Functional foods that may be effective for blood lipid management include soluble fibre, plant stanols and sterols, psyllium, flaxseed, a variety of nuts, omega-3 fatty acids, garlic, flavonoids found in dark chocolate and soy protein 27 EFFECTS OF GRAPEFRUIT • The chemicals in grapefruit do not interact directly with statin medications. Rather these chemicals bind to an intestinal enzyme, blocking its action and making the passage of the medication easier from gut to bloodstream • As a result, blood medication levels may rise faster and remain at higher than normal levels, and in some cases abnormally high levels are dangerous • Regarding statins and grapefruit use, some statins are affected more than others. For example, atorvastatin (Lipitor), simvastatin (Zocor) and lovastatin (Mevacor), blood levels are boosted more than when fluvastatin (Lescol), pravastatin (Pravachol) or rosuvastatin (Crestor) is the prescribed medication. • As a recommendation, any grapefruit product should be avoided when taking a statin 28 PHYSICAL ACTIVITY AND EXERCISE • The health benefits of regularly practiced physical activity, such as improved triglyceride and HDLc concentrations, blood pressure, blood glucose control and cardiovascular function, will be enjoyed regardless of weight change or in the absence of noticeable improvements in fitness 29 WEIGHT LOSS • Weight loss is a top priority for overweight and obese patients with dyslipidaemia • The current recommendations are to achieve a 7 – 10% reduction in body weight over a 6 – 12 month period through caloric restriction and increased physical activity • Weight loss achieved through healthy lifestyle behaviour may be the most effective means of preventing and treating dyslipidaemia • Additional health benefits can be realised with greater weight loss and long-term maintenance of the lower body weight 30 PHARMACOLOGY: LIPID-LOWERING MEDICATIONS 31 PHARMACOLOGY: LIPID-LOWERING MEDICATIONS • The primary targets for lipid-lowering therapy is LDLc and non-HDLc • Statin therapy is by far the primary drug used to lower LDLc • Among the statins, rosuvastatin exhibits the greatest effects • In standard dosages, statins can reduce LDLc by as much as 40%, but are limited in their efficacy for lowering triglycerides, increasing HDLc, and modifying other aspects of atherogenic dyslipidaemia like small, dense LDL particles 32 PHARMACOLOGY: LIPID-LOWERING MEDICATIONS • In addition to lipid-lowering effects, statin treatment may reduce serum uric acid levels, improve renal function and lower CVD events in patients with metabolic syndrome and diabetes mellitus • Statins inhibit cholesterol production in the liver and increase LDL receptor numbers in hepatic and other tissues • Downstream effects are stabilisation of atherosclerotic lesions and decreasing endothelial dysfunction • The most common side effects reported with statin therapy are elevated liver enzymes, myopathy, myalgia and dyspepsia 33 PHARMACOLOGY: LIPID-LOWERING MEDICATIONS • Elevated fasting and postprandial triglycerides; low HDLc; and small, dense LDL particles contribute to residual CVD risk after LDLc goals have been achieved • HDLc, essentially a marker of reverse cholesterol transport, becomes a focus of lipid management after LDLc, non-HDLc and triglyceride values have been addressed. Currently, there are no clinical targets for raising HDLc 34 PHARMACOLOGY: LIPID-LOWERING MEDICATIONS • Fibrates and niacin are effective for lowering triglycerides, increasing HDLc and increasing LDL particle size • As such, these agents are chosen to address atherogenic dyslipidaemia – either as first-line therapy when LDLc is within normal limits or in combination with statins • The combination of simvastatin and fenofibrate appears to have an additive and powerful effect on ameliorating all atherogenic characteristics of the lipid and lipoprotein profile • Niacin also has the added benefit of lowering lipoprotein and fibrinogen levels and, in combination with simvastatin, shows promise in decreasing CVD events 35 PHARMACOLOGY: LIPID-LOWERING MEDICATIONS • A longstanding limitation for niacin has been that it is not well tolerated, although extended-release forms have improved tolerance • Niacin therapy often results in flushing, skin rashes, gastrointestinal problems and pruritus • Niacin is not recommended for individuals with hypotension, liver dysfunction or peptic ulcers or for those with diabetes mellitus, as it often causes increases in blood glucose concentrations • You should remind patients to take niacin before going to sleep at night to avoid these unwanted side effects during the day and especially with exercise • You should also make patients aware of these side effects to distinguish between the effect of the drug and what might be experienced during exercise 36 PHARMACOLOGY: LIPID-LOWERING MEDICATIONS • Up to 25% of patients taking lipid-lowering medications, particularly statins and fibric acid derivatives, may experience some form of medication intolerance that includes muscle inflammation or muscle damage • Rhabdomyolysis – A severe side effect arising from medication-induced muscle damage, is characterised by the presence of myoglobin in the blood, reduced and dark urine output and a general feeling of weakness. • Since kidney damage may result, a patient experiencing these symptoms should immediately contact their Physician 37 PHARMACOLOGY: LIPID-LOWERING MEDICATIONS • Bile acid sequestrants are considered for persons who remain resistant to the lipid-lowering effects of statins and for younger individuals facing long-term pharmacologic management of dyslipidaemia • In summary, choosing to follow a Mediterranean-style diet, incorporating functional foods in the diet, exercising regularly and losing weight are each effective means for improving blood lipid levels • If patients respond conservatively to each of these therapeutic lifestyle changes, they may expect to lower LDLc and triglyceride levels and improve HDLc to the same magnitude that would be expected with lipid-lowering medications 38 PHARMACOLOGY: LIPID-LOWERING MEDICATIONS • For patients who are not on lipid-lowering medication, the lifestyle strategies could be enough to keep them off these medicines • For patients already taking these drugs, lifestyle strategies may add to their medicine’s effect • For all patients, these therapeutic lifestyle changes will provide health benefits above and beyond what can be attained with lipid-lowering medication alone 39 EXERCISE PRESCRIPTION • Exercise can have a profound impact either directly or indirectly (ie. weight changes) on blood lipid and lipoprotein levels • While various exercise modalities can provide health benefits that may ultimately improve lipid status, the majority of evidence suggests that cardiorespiratory exercise is preferred, although a yet-defined combination program may be optimal • Nevertheless, the specific doses for optimising improvements have not yet been completely defined 40 CARDIORESPIRATORY EXERCISE • There is a dose-response relationship between cardiorespiratory exercise and cholesterol outcomes • The lipid- and lipoprotein-related benefits of physical activity rely more on the total volume of activity performed than on the intensity of the activity • Physical activity can directly affect the metabolism of some lipids and lipoproteins, while alteration of others may depend on changes in body composition 41 CARDIORESPIRATORY EXERCISE • While progressing toward 300 minutes/week of moderate-intensity or 150 minutes/week of vigorousintensity physical activity is recommended, little research is available to suggest the number of days per week the activity should be performed • Studies employing single sessions of exercise typically show that lipid and lipoprotein concentrations change the most 1 or 2 days afterward and that they return toward baseline by 3 days. Thus, a sensible approach might be to allow no more than 1 or 2 inactive days between exercise sessions 42 CARDIORESPIRATORY EXERCISE • People should accumulate 150 to 300 minutes of moderateintensity or 75 to 150 minutes of vigorous-intensity dynamic physical activity using large muscle groups, or some combination of the two, throughout each week • To optimise lipid and lipoprotein changes, clients are encouraged to progress to the upper end of the exercise dose range • Leisure-time physical activity should be practiced on at least 3 days through the week, and 5 or more days are required for most people to meet the dose recommendations • Moderate- to vigorous-intensity physical activity may be accumulated throughout the day and does not necessarily need to be accomplished within a single daily session 43 RESISTANCE EXERCISE • Resistance training alone may have very limited effect on improving blood lipid and lipoprotein concentrations • Since cardiorespiratory exercise should be prioritised, more than one set per resistance training exercise is not recommended unless the client is clearly motivated to be compliant with both cardiorespiratory and resistance exercise 44 RANGE OF MOTION EXERCISE • ROM exercise provides no known benefit to lipid or lipoprotein profiles • Unless certain comorbidities exist, there are no special considerations for dyslipidaemic patients with respect to ROM exercise 45 EXERCISE PRESCRIPTION SUMMARY 46 EXERCISE TRAINING – CARDIOVASCULAR EXERCISE • There is strong evidence for lower tricglyceride and greater HDLc concentrations in physically active individuals • Triglyceride levels are almost always lower in endurance athletes, aerobically trained people and physically active individuals when compared with sedentary controls • Blood levels of HDLc are between 9% and 59% higher in those having physically demanding jobs and in individuals engaged in endurance exercise compared with their less active counterparts • There is only limited evidence to suggest that people who are physically active exhibit lower concentrations of total cholesterol and LDLc than those who are less active 47 EXERCISE TRAINING – CARDIOVASCULAR EXERCISE • Total cholesterol and LDLc infrequently change with exercise training in either men or women. When these lipid fractions are altered with exercise training, the reductions are minimal or moderate, averaging only 4 – 7% when compared with values in non-exercising control subjects • When HDLc is significantly elevated after exercise training, the increases are similar in men and women, ranging from 4 – 22% • In addition to increasing HDLc, exercise boosts the antioxidant properties of HDL • Combined with reductions in triglyceride, the elevated antioxidant potential of HDL is thought to attenuate the inflammation and oxidative stress that contribute to vascular dysfunction and ASCVD 48 EXERCISE TRAINING – CARDIOVASCULAR EXERCISE • Significant reductions in triglyceride concentrations range from 4 – 37% after aerobic exercise training in males; the magnitude of change is similar in women but is seen less frequently • Resistance training also has positive but more modest effects on blood lipid and lipoprotein concentrations than observed for aerobic exercise 49 EXERCISE TRAINING – CARDIOVASCULAR EXERCISE • A single aerobic exercise session of sufficient volume can raise serum HDLc. The post-exercise increase in HDLc is strikingly like what is generally attributed to long-term endurance exercise training. However, HDLc levels peak 24 – 48 hours after exercise and last up to 72 hours before returning to pre-exercise levels • An exercise energy expenditure threshold of about 350 kcal is enough to elevate HDLc in deconditioned individuals, but a caloric expenditure threshold of 800 kcal or more may be needed in those who are well conditioned 50 EXERCISE TRAINING – CARDIOVASCULAR EXERCISE • A single session of endurance exercise lowers blood triglyceride concentrations and this exercise effect is observed in apparently healthy normo- and hyperlipidaemic individuals • Similar to the HDLc responses to a single exercise session, the exercise effect on serum triglyceride is influenced by the training status of the subjects and volume of exercise performed. Regardless of the mode or intensity, the exercise effect is lost after 48 – 72 hours 51 EXERCISE TRAINING – CARDIOVASCULAR EXERCISE • Existing evidence also suggests a relationship between pre-exercise triglyceride concentration and the magnitude of post-exercise change. • In other words, people with elevated pre-exercise serum triglyceride concentrations exhibit the greatest post-exercise reductions, while those with relatively low pre-exercise triglyceride concentrations show only modest or no change after exercise 52 EXERCISE TRAINING – RESISTANCE EXERCISE • Resistance exercise appears to have a small beneficial influence on blood lipids that is somewhat similar to what is reported for endurance exercise • As relatively fewer calories are expended in resistance versus aerobic activity, resistance training per se may be less effective than endurance activities for modifying blood lipid levels • Above all, remember that stable lipid and lipoprotein changes sometimes take several months to achieve 53 LIPID AND LIPOPROTEIN CHANGES WITH EXERCISE - SUMMARY 54 WEEKLY READINGS K., E. J. (2022). Clinical Exercise Physiology (5th ed.). Chapter 11: Hyperlipidemia and Dyslipidemia. Human Kinetics Publishers. 55 55