Hypercholesterolemia

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Reducing low-density lipoprotein cholesterol (LDL-C) appears to reduce the risk of coronary heart disease events and coronary heart disease mortality in both males and females. It may also improve all-cause mortality in males but not in females. General exercise is effective for reducing hypercholesterolemia and may also be able to decrease both total cholesterol and LDL-C while increasing HDL-C in healthy, obese and overweight, hypercholesterolemic and many other diseased populations.

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What is hypercholesterolemia?

Hypercholesterolemia is the presence of elevated levels of cholesterol in the blood. It is a sub-category of hyperlipoproteinemia, which is the presence of elevated levels of lipoproteins (combined fat and protein molecules) in the blood, which is itself a sub-category of hyperlipidemia, or the presence of elevated levels of lipids (fats) in the blood (Durrington). Cholesterol is transported in the blood within the lipoproteins, which are molecules that have a globular shape and are a combination of lipid (fat) and protein. The center of a lipoprotein is made up of lipid, primarily triacylglycerol and cholesteryl ester, while the outer membrane is made up of phospholipids, a small amount of free cholesterol and proteins called apolipoproteins (Biggerstaff and Wooten).

Lipoproteins are classified by their density: very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). The cholesterol content of these molecules is often referred to using the suffix –C, e.g. LDL-C for low density lipoprotein cholesterol. The classification of lipoproteins in this way is important for an understanding of coronary heart disease risk as the different types of molecule perform different roles. Specifically, excessive delivery of cholesterol to the artery walls by VLDL and LDL-type lipoproteins is thought to be associated with atherosclerotic plaque accumulation and increased risk of coronary heart disease. For example, a recent systematic review found that a 0.26 mmol/L reduction in serum LDL-C was associated with a relative risk reduction of 7.2% for coronary heart disease deaths and 7.1% for coronary heart disease events (Briel). Because of this, serum levels LDL-type lipoproteins are often termed “bad cholesterol” while levels of HDL-type lipoproteins are often termed “good cholesterol” (Biggerstaff and Wooten).

However, rather than assess serum LDL-C individually, some researchers have proposed that it is more useful to assess the presence of serum HDL-C and non-HDL-C. Non-HDL-C is calculated by subtracting HDL-C from total cholesterol, and it reflects circulating levels of the atherogenic apolipoprotein-B–containing lipoproteins including LDL-C, VLDL-C, IDL-C, chylomicron remnants, and Lp(a), which is a specific form of LDL-C. Some epidemiological studies have reported that levels of serum non-HDL-C may be a superior predictor of cardiovascular risk compared with serum levels of LDL-C (e.g. Cui et al.).


How does hypercholesterolemia relate to mortality?

As noted in the preceding section, elevated levels of serum LDL-C are generally thought to place individuals at an increased risk of coronary heart disease mortality and consequently (all other things being equal) all-cause mortality. The following table sets out some recent meta-analyses of randomized controlled trials exploring the relationship between LDL-C and coronary heart disease mortality and all-cause mortality:

Study Method Finding
De Lemos et al. The reviewers performed a meta-analysis of 26 randomised controlled trials involving >1,000 participants and >2 years' treatment duration of varying or no statin treatments to reduce serum levels of LDL-C with a median follow-up period of 5.1 years. The reviewers found that for each 1.0 mmol/L reduction in LDL-C, there was a risk reduction of 22% for major cardiovascular events, a risk reduction of 20% in cardiovascular mortality as a result of coronary heart disease, and a risk reduction of 10% for all-cause mortality.
Robinson et al. The reviewers performed a meta-analysis of randomized, placebo-controlled, or active-controlled trials > 2 years’ duration that assessed various treatments for reducing LDL-C, including 14 statin trials, 7 fibrate trials, 7 niacin trials and 3 other trials with a mean follow-up period of 4.5 years. The reviewers found that for statins, a 1% decrease in non–HDL-C was associated with an estimated reduction in 4.5-year coronary heart disease incidence of 1%. The reviewers noted that the other treatments produced similar results.
Ray et al. The reviewers performed a meta-analysis of randomized trials of statins vs. placebo or control that recorded information about LDL-C levels and all-cause mortality in individuals without prevalent cardiovascular disease at baseline. The reviewers identified 11 trials for inclusion in their review, encompassing 65,229 subjects over 244,000 person-years of follow-up and 2,793 deaths. The reviewers found that there was no significant relationship between mean baseline levels of LDL-C and all-cause mortality.
Baigent et al. The reviewers performed a meta-analysis of randomised trials testing an intervention to modify lipid levels in populations of >1000 subjects over >2 years with a mean follow-up period of 4.7 years. The reviewers observed a 12% reduction in all-cause mortality per mmol/L reduction in LDL-C. However, they also noted that this reduction in all-cause mortality risk was attributable mainly to a 19% reduction in coronary heart disease risk deaths.
Gould et al. The reviewers performed a meta-analysis of all trials published in English that assessed the effects of lipid-modifying therapies on all-cause mortality. The reviewers found 62 studies involving 216,616 patients. The reviewers reported that for each 1-mmol/L decrease in total cholesterol, there was a 17.5% reduction in the risk of all-cause mortality, which was attributable to the 24.5% reduction in coronary heart disease-related mortality.
Marchioli et al. The reviewers performed a review of randomized clinical trials of cholesterol-lowering interventions for the prevention of coronary heart disease. The reviewers found 34 trials with cholesterol-lowering interventions in 24,968 individuals. The reviewers found that all-cause mortality was reduced by 13% in the intervention groups in comparison with the control groups but baseline total cholesterol levels had no clear influence on all-cause mortality.
Montague et al. The reviewers assessed epidemiologic studies, primary and secondary prevention trials with clinical end points, and secondary prevention trials with quantitative coronary angiography as a surrogate end point for clinical coronary heart disease to see whether cholesterol-lowering treatments were effective for reducing all-cause mortality. The reviewers found that while cholesterol-lowering treatments were effective for reducing coronary heart disease events and coronary heart disease mortality, they were not effective for reducing all-cause mortality.
Cholesterol Treatment Trialists' Collaboration The reviewers performed meta-analyses of data from randomised trials involving >1000 participants and of >2 years' duration comparing 5 different statin regimens and 21 statin versus control trials. The reviewers found that across all 26 trials, all-cause mortality was reduced by 10% per 1.0 mmol/L reduction in LDL-C, which was attributable mainly to a more significant reduction in coronary heart disease mortality of 20%.
Cholesterol Treatment Trialists' Collaboration The reviewers performed meta-analyses of data from randomised trials involving >1000 participants with no prior history of vascular disease and of >2 years' duration comparing 5 different statin regimens and 22 statin versus control trials. The reviewers found that across all 27 trials, all-cause mortality was reduced by 9% per 1.0 mmol/L reduction in LDL-C, which was attributable mainly to a more significant reduction in coronary heart disease mortality of 15%.
Walsh and Pignone The reviewers performed a meta-analysis to assess the effects of lipid-lowering treatments in females. They included studies that had a duration of >1 year and which recorded all-cause mortality and coronary heart disease mortality. The reviewers found 13 studies, of which 6 trials included a total of 11,435 women without cardiovascular disease and assessed the effects of lipid-lowering medications. The reviewers reported that lipid lowering in this population did not reduce total mortality, coronary heart disease mortality or even coronary heart disease events. In the 8 trials that included 8,272 women with cardiovascular disease, the reviewers found that lipid lowering did not reduce all-cause mortality but did reduce coronary heart disease mortality 26% and the risk of coronary heart disease events by 20%.
Perk et al. Based on the study performed by De Lemos et al., current guidelines from the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice provided guidance regarding the effects of LDL-C reduction on cardiovascular mortality. The reviewers suggest that each reduction of 1.0 mmol/L in LDL-C is associated with a corresponding 20 – 25% reduction in cardiovascular mortality and non-fatal myocardial infarction. However, this guidance did not discuss the other, contradictory reviews and meta-analyses.

Based on these meta-analytic reviews and guidance documents, it seems likely that reducing low-density lipoprotein cholesterol (LDL-C) does reduce the risk of coronary heart disease events and coronary heart disease mortality in both males and females, and possibly also all-cause mortality in males (although the literature is conflicting) but not females.


How does hypercholesterolemia relate to mortality in elderly people?

As noted in the preceding section, elevated levels of LDL-C are generally thought to place males at an increased risk of coronary heart disease mortality and possibly all-cause mortality (although the data is conflicting). This conclusion is made on the basis of studies showing interventions using treatments designed to lower cholesterol levels. However, such studies have infrequently been conducted in elderly people. One randomised controlled trial (Shepherd et al.) assessed the effects of pravastatin treatment in 5,804 men elderly people aged 70 – 82 years with a history of, or risk factors for, vascular disease. The researchers randomly allocated the subjects to either a pravastatin treatment or to a placebo. The researchers found that while pravastatin lowered LDL-C concentrations by 34% and reduced the incidence of coronary heart disease events and mortality by 15% and 19%. However, there was no effect on all-cause mortality.

Currently, as a result of this trial and the lack of subsequent trials, the effects of cholesterol lowering treatments in elderly populations are therefore regarded as controversial. However, the epidemiological data is more clear. The following table sets out some recent studies exploring the association between LDL-C and coronary heart disease mortality and all-cause mortality in elderly people:

Study Method Finding
Krumholz et al. The researchers performed a prospective, community-based cohort study to assess whether elevated total cholesterol levels were associated with all-cause mortality in persons >70 years of age. The researchers found that elevated total cholesterol levels were not associated with a significantly higher rate of all-cause mortality, coronary heart disease mortality, or hospitalization for a coronary heart disease event.
Corti et al. The researchers carried out a study to assess whether there is an association between total cholesterol level and coronary heart disease mortality and all-cause mortality in older adults. The researchers found that persons with the lowest total cholesterol levels (<4.15 mmol/L or 160 mg/dL) had the highest rate of death from coronary heart disease, while those with elevated total cholesterol levels (>6.20 mmol/L or >240 mg/dL) had a lower risk for death from coronary heart disease.
Benfante et al. The researchers assessed the association between total cholesterol level and coronary heart disease mortality and all-cause mortality in males aged > 65 years. They recruited 1480 men and followed up over an average of 12 years. The researchers found that the incidence of coronary heart disease increased progressively from the lowest to the highest quartile of total serum cholesterol level.
Weverling-Rijnsburger et al. The researchers assessed the association between total serum cholesterol levels on specific and all-cause mortality in people aged >85 years. The researchers found that in 724 participants with a median age of 89 years, each 1 mmol/L increase in total cholesterol corresponded to a 15% decrease in mortality. The researchers found that mortality from cancer and infection was significantly lower among the participants in the highest total cholesterol category than in the other categories, which largely explained the lower all-cause mortality in this category.
Kronmal et al. The researchers assessed the association between total serum cholesterol levels on specific and all-cause mortality as a function of age using the biennial examination data from 1948 – 1980 for the 5,209 men and women enrolled in the Framingham Heart Study. The researchers found that the relationship between total cholesterol level and all-cause mortality was positive (i.e. a higher cholesterol level was associated with higher mortality) at age 40 years, negative at age 80 years and non-existent at ages 50 – 70 years.
Zimetbaum et al. The researchers performed a trial to assesse prospectively the association between total serum cholesterol levels on specific and all-cause mortality. The Bronx Aging Study was a 10-year prospective investigation of very elderly subjects (mean age at entry: 79 years) without terminal illness or dementia. The researchers found that consistently low HDL-C levels was associated with higher all-cause mortality in men but not women. They did not find any other associations between lipid levels and all-cause mortality, whether negative or positive.
Schatz et al. The researchers assessed changes in both lipid and serum cholesterol concentrations prospectively over 20 years and compared them with all-cause mortality in in 3,572 Japanese/American men aged 71 – 93 years as part of the Honolulu Heart Program. The researchers divided the subjects into four quartiles of increasing levels of serum cholesterol concentrations. The researchers found that in comparison with the first quartile with the lowest serum cholesterol concentrations, the second, third and fourth quartiles had a 28%, 40% and 35% lower all-cause mortality risk. The researchers suggest that their data cast doubt on the scientific justification for lowering cholesterol in elderly people.

Based on these studies, it seems likely that reducing serum levels of low-density lipoprotein cholesterol (LDL-C) does not reduce the risk of coronary heart disease events, coronary heart disease mortality and all-cause mortality in elderly people. Rather, it may in fact increase the risk of death.


What is the prevalence of hypercholesterolemia?

Hypercholesterolemia is defined as elevated serum total cholesterol but the exact cut points vary between research groups. Studies have mostly used levels of either >200mg/dL (>5.2 mmol/L) or >240mg/dL (>6.2 mmol/L) on the day of survey and/or current use of cholesterol lowering medication to indicate hypercholesterolemia. However, irrespective of the exact definition, it is clear that hypercholesterolemia is extremely common in most modern populations, as shown in the table below:

Study Population Definition Prevalence
Al-Nuaim et al. Saudi Arabian males aged >15 years 200mg/dL 9%
Al-Nuaim et al. Saudi Arabian females aged >15 years 200mg/dL 11%
Arnett et al. Males aged 35 – 74 years in Minnesota, United States 200mg/dL 54.9%
Arnett et al. Females aged 35 – 74 years in Minnesota, United States 200mg/dL 46.5%
Sprafka et al. White males aged 35 – 74 years in the Twin Cities, United States 240mg/dL 18.3%
Sprafka et al. Black males aged 35 – 74 years in the Twin Cities, United States 240mg/dL 12.2%
Sprafka et al. White females aged 35 – 74 years in the Twin Cities, United States 240mg/dL  19.7%
Sprafka et al. Black females aged 35 – 74 years in the Twin Cities, United States 240mg/dL  16.6%
Szklo et al. Individuals aged 45 – 64 years in the United States 240mg/dL 25.3%
Santiago et al. Portuguese boys aged 5 – 17 years of age 240mg/dL 15.1%
Santiago et al. Portuguese girls aged 5 – 17 years of age 240mg/dL 20.3%
Posadas-Romero et al. Mexican adults >20 years of age 200mg/dL 22.8%
Wander et al. Punjab Indian adults aged > 30 years 240mg/dL 7.0%
He et al. Chinese individuals aged 35 – 74 years 240mg/dL 9.0%
Schargrodsky et al. Individuals from 7 Latin American countries 240mg/dL 14%

Based on the above studies, it seems that the prevalence of hypercholesterolemia as defined by >240mg/dL (6.2mmol/L) can range from 7.0 – 25.3% depending upon the exact age, gender and ethnic background of the individuals being tested.


What risk factors are associated with hypercholesterolemia?

The following table sets out several  studies that have been performed that assess the varying factors that contribute to a greater or lesser risk of hypercholesterolemia in various populations:

Study Method Finding
Williams and Thompson The researchers performed a prospective cohort study to assess the health benefits of both walking and running exercise of equivalent energy expenditure. They made use of the National Runners' Health Study cohort (33,060 people) and the National Walkers' Health Study cohort (15,945 people) and explored the differences between the cohorts in respect of coronary heart disease risk factors, including hypercholesterolemia, when energy expenditure was matched between the groups. The researchers found that running significantly decreased the risks for hypercholesterolemia by 4.3% while walking reduced the risk by 7.0%. They observed that the risk reduction for hypercholesterolemia was marginally greater for walking than running, where energy expenditure was matched.
Vaccaro and Huffman The researchers set out to assess the associations of lifestyle medical advice and non-HDL cholesterol control of a nationally representative US sample of adults with hypercholesterolemia. They used data from two cycles of the National Health and Nutrition Survey (2007 – 2008 and 2009 – 2010), which including data from 11,577 male and female adults aged >20 years, grouped by race (Mexican American, other Hispanic, Black non-Hispanic or White non-Hispanic). The researchers found that of those who had received medical advice, reporting currently controlling or losing weight" was associated with lower non-HDL cholesterol."
Chitra et al. The researchers performed a hospital-based cross-sectional study to assess the associations between diet, exercise and serum lipid profile in 316 healthy men and women >20 years of age visiting the lifestyle clinic of CARE Hospitals, Hyderabad, India for health check-up. The researchers found that 28.5% of the males and 42.2% of the females had hypercholesterolemia. The researchers reported that bodyweight and waist circumference were significantly associated with total cholesterol and LDL-C cholesterol and waist circumference was also positively correlated with triglycerides. Additionally, the researchers found that a low level of physical activity was positively associated with total cholesterol levels.
Hassapidou et al. The researchers performed a cross-sectional study to assess the association between physical activity and sedentary lifestyle patterns with overweight, obesity, abdominal adiposity and cardiometabolic risk factors in 17,887 Greek males and females, aged 20 – 70 years old. The researchers found that those individuals who exercised for >7 hours per week had a 55% lower risk of hypercholesterolemia while those individuals who watched television for >16 hours per week and performed office work >14 hours per week had 20% and 55% increased risks of hypercholesterolemia, respectively.
Lee et al. The researchers assessed the associations between changes in fitness and fatness with the subsequent incidence of the cardiovascular disease risk factors of hypertension, metabolic syndrome, and hypercholesterolemia in 3,148 healthy adults over a 6-year follow-up period. The researchers found that maintaining or improving fitness was associated with lower risk of developing hypercholesterolemia, while increasing fatness was associated with higher risk of developing hypercholesterolemia. Specifically, those who maintained or improved fitness had a 26% and 30% lower risk of hypercholesterolemia, respectively, compared with those who lost fitness, while those who gained body fat had a 48% higher risk of hypercholesterolemia compared with those who lost body fat.
Fang et al. The researchers used the 2007 Behavioral Risk Factor Surveillance System to assess the association between consumption of >5 servings of fruits and vegetables per day and Healthy People 2010 recommended levels of physical activity and the incidence of hypercholesterolemia in 363,667 adults aged >18 years. The researchers reported that in the sample of adults, 37.3% displayed hypercholesterolemia. The researchers found that the percentages of individuals eating >5 servings of fruits and vegetables per day and engaging in recommended levels of physical activity were lower among those with hypercholesterolemia than among those without (23.8% vs. 27.9% for healthy eating and 43.1% vs. 51.7% for physical activity).
Lentino et al. The researchers assessed differences in physical activity and cardiometabolic risk factors between dog owners who did or did not walk their dogs and adults who do not own dogs. The researchers found that those who did not own or walk a dog reported lower levels of physical activity and a higher body mass index (BMI) than dog owners who walked their dogs. Additionally, the researchers found that after adjusting for age and moderate-to-high levels of physical activity, those who did not own dogs had a significantly greater risk (1.72 times) of compared with dog owners who regularly walked their dogs.
Bouillon et al. The researchers performed a prospective cohort study (the Whitehall II study) to assess the association between lipid-lowering drugs, change in diet and change in physical activity with LDL-C in 4,469 middle-aged British civil servants (72% males) aged 39 – 62 years at baseline over an 11-year follow-up period. The researchers found that LDL-C decreased by -1.14 mmol/L in those who were taking lipid-lowering treatment at baseline and by 1.77 mmol/L in those who started treatment during the follow-up compared with untreated individuals. They also found that LDL-C decreased by 0.10 mmol/L in those who increased their levels of physical activity compared with those who maintained or decreased their levels of physical activity.
Williams The researcher assessed the prevalence of hypertension, hypercholesterolemia and diabetes in relation to marathon participation independent of annual running mileage. The researcher found that in comparison with non-marathoners, men who averaged 0.2 – 0.8 marathons per year had a 22% lower chance of using LDL-cholesterol-lowering medication. The researcher also found that marathon participation was also associated with lower LDL-cholesterol-lowering medication use in females but not when adjusted for annual distance run.
Williams The researcher assessed whether changes in the volumes of vigorous exercise affect the risk of hypercholesterolemia in recreational runners. The researcher followed a cohort of recreational runners and compared the risk of hypercholesterolemia between those whose weekly running distance increased >0.5 km per day, remained constant, or decreased >0.5 km per day over a 7.8 year follow-up period. The researcher found that in comparison with those runners who maintained or decreased running volume, the risk of hypercholesterolemia for those whose running increased was significantly reduced and was 18% lower in males and 29% lower in females.
Williams The researcher assessed the association between running intensity and the use of antihypertensive, LDL-C-lowering medication when adjusted for running volume. The researcher reported that when adjusted for volume (kilometers per day), each unit increase in running speed (meter-per-second) reduced the odds for LDL-C-lowering medication use by 55% and 48%, in males and females respectively.
Williams The researcher assessed the association between cardiovascular fitness and hypercholesterolemia, independent of activity in in 29,139 male and 11,985 female recreational runners who were followed prospectively for 7.7 and 7.4 years, respectively. During the period of the follow-up, the researcher observed 3,330 men (12.2%) and 599 women (5.14%) became hypercholesterolemic. The researcher reported that  longer running distance (miles per week) at baseline predicted lower incident hypercholesterolemia (men and women) during follow up. The odds for hypercholesterolemia decreased significantly with each additional 16km per week increment in distance up to 64km per week in men and 48km per week in women. Additionally, the researcher reported that higher baseline cardiovascular fitness predicted significantly lower odds for hypercholesterolemia in both men and women, independent of distance. Compared to the least fit men, the fittest males had 67% lower odds for becoming hypercholesterolemic.
Williams and Hoffman The researchers  assessed the association between cardiovascular fitness and hypercholesterolemia, independent of activity in in 29,139 male and 11,985 female recreational runners who were followed prospectively for 7.7 and 7.4 years, respectively. The researchers reported that relative to males with BMI < 20 kg/m2, the odds for being diagnosed with hypercholesterolemia increased by 64% and 135% for those with a BMI of 20 – 22.5 kg/m2 and 22.5 – 25 kg/m2, respectively. Similarly, for females, the odds for being diagnosed with hypercholesterolemia increased by 29% and 41% for those with a BMI of 20 – 22.5 kg/m2 and 22.5 – 25 kg/m2, respectively.
Sakuta and Suzuki The researchers assessed the association between duration of physical activity and cardiovascular risk factors in middle-aged male military personnel. The researchers reported that duration of high-intensity physical activity but not that of moderate- or low-intensity physical activity was inversely correlated with body mass index (BMI), triglycerides, fasting plasma glucose, white blood cell count and systolic blood pressure. However, no intensity categories of physical activity were correlated with total cholesterol.
Ruixing et al. The researchers assessed the association between diet and lifestyle factors and hyperlipidemia in middle-aged and elderly persons between the Guangxi Bai Ku Yao and Han populations in China. The researchers found that hyperlipidemia was positively correlated with body mass index, waist circumference, total fat and intake of saturated fatty acids but negatively associated with sex (women were higher), physical activity and total dietary fiber intake.
McMurray et al. The researchers assessed the association between aerobic power (VO2-max), physical activity and hypercholesterolemia. The researchers reported that in comparison with individuals in the lowest tertile of VO2-max, those in the highest tertile had a 44% lower risk of hypercholesterolemia. However, there was no difference in respect of physical activity.
Tucker and Bagwell The researchers assessed the association between aerobic fitness and total cholesterol/HDL-C ratios >5.0mmol/L in 10,455 adults. The researchers found that high fitness levels were associated with a low prevalence of elevated ratio of total cholesterol to HDL-C. After controlling for the potential confounders, adults classified as having excellent aerobic fitness levels 64% less likely to have an elevated ratio of total cholesterol to HDL-C compared to poorly fit adults. The researchers also observed that high-level fitness was also associated with high HDL-C levels and low total cholesterol levels.
Durstine et al. The reviewers assessed the dose-response of blood lipids to exercise observed in various cross-sectional studies. The reviewers reported that most sedentary individuals will display elevations in HDL-C of 3.5 – 6 mg/dL by increasing their exercise energy expenditure to 1500 – 2200 kcal per week. They reported that further increases in HDL-C of 1.5 – 3 mg/dL can be expected for each additional 1,100 kcal per week of exercise energy expenditure. The reviewers reported that reductions in triglycerides of 7 – 20mg/dL are displayed by sedentary individuals adopting an energy expenditure of 1500 – 2,200 kcal per week and further reductions of 3 – 8mg/dL may occur for each 1,100 kcal per week of exercise energy expenditure. However, the reviewers observed that there is little support in the cross-sectional literature for significant changes in either total cholesterol or LDL-C as a result of exercise energy expenditure, independently of body fat loss.

Based on these studies, it appears that physical activity (including walking and running) and weight-loss or control programs are associated with a lower risk of hypercholesterolemia while being overweight or obese is associated with an increased risk of hypercholesterolemia.


Does exercise improve cholesterol levels in healthy people?

A number of exercise interventions have been performed to assess the effects of general exercise, physical activity or aerobic exercise on cholesterol levels in healthy populations, as shown in the table below:

Study Method Finding
O'Donovan et al. The researchers assessed the effects of exercise intensity on coronary heart disease risk factors in 64 previously sedentary men. The researchers randomly allocated the subjects to a control group, a moderate-intensity exercise group (performing 3 sessions of 400-kcals per week at 60% of VO2-max), or a high-intensity exercise group (performing 3 sessions of 400-kcals per week at 80% of VO2-max) for a 24-week period. The researchers found significant changes in total cholesterol (0.55 ± 0.81mmol/L), LDL-C (0.52 ± 0.80mmol/l), and non-HDL-C (0.54 ± 0.86mmol/L) only in the high-intensity group, which may suggest that high-intensity training is more effective in improving coronary heart disease risk factors than lower exercise intensities.
Farag et al. The researchers assessed a school-based work-site physical activity program in a rural public school system in Southwestern Oklahoma. During the 2005-2006 school year, 187 subjects (mean age 45 years) were screened for cardiovascular risk factors and then took part in an activity program before being screened again after 6 months. The researchers found that at the post-intervention screening, the subjects had lower total cholesterol (193 ± 2.6 to 181 ± 2.3mg/dL), LDL-C (114 ± 2.5 to 109 ± 2.1mg/dL) and HDL-C (54 ± 1.1 to 47 ± 1.0mg/dL) as well as higher self-reported physical activity levels.
Sarrafzadegan et al. The researchers assessed the effects of a comprehensive, community-based healthy lifestyle program (the Isfahan Healthy Heart Program) on Cardiometabolic risk factors, including hypercholesterolemia, using a quasi-experimental design. The program targeted the general population (2,180,000 people) in 3 districts in central Iran. Data from independent sample surveys before (2000 – 2001) and after (2007) were used to assess the effects of the program. The program comprised 4 main strategies: healthy nutrition, increased physical activity, tobacco control and coping with stress. The researchers found that the prevalence of abdominal obesity, hypertension, hypercholesterolemia, hypertriglyceridemia and high LDL-C decreased significantly in the intervention area versus the reference area for both males and females. However the reduction in overweight and obesity was significant only for females. Specifically, the prevalence of hypercholesterolemia in the intervention area decreased significantly from 23.5% to 12.5% in females and significantly from 18.5% to 9.6% in males. However, the prevalence of hypercholesterolemia in the reference area also decreased significantly in males ((14.4% to 9.8%).
LeMura et al. The researchers assessed effects of both aerobic exercise and resistance training on serum lipoprotein-lipid profiles over a 16-weeks exercise and 6-week detraining period in 48 young women. The researchers randomly allocated the subjects to either a control group, an aerobic exercise group, a resistance training group, or a combined aerobic and resistance training group. The researchers found that the aerobic group displayed significantly reduced triglycerides and significantly increased HDL-C after 16 weeks of training but did not alter total cholesterol or LDL-C. The resistance training and combined training groups did not change total cholesterol, triglycerides, LDL-C or HDL-C.
Inoue et al. The researchers assessed the effects of a 6-month health education program, including advice regarding increased amounts of physical activity. The researchers reported that total cholesterol, triglyceride, and atherosclerosis-index levels significantly decreased while HDL cholesterol levels significantly increased as a result of the intervention.
Stefanick et al. The researchers assessed the effects of diet and exercise interventions on lipoprotein levels in 180 postmenopausal women, 45 – 64 years of age and 197 men, 30 – 64 years of age, with low HDL-C levels and moderately elevated levels LDL-C levels. The researchers randomly allocated the subjects to either an aerobic exercise group, a diet group, a combined diet plus exercise group, or a control group. The researchers reported that HDL-C and triglyceride levels and the ratio of total cholesterol to HDL-C did not differ significantly between treatment groups. LDL-C significantly reduced in females by 14.5 ± 22.2mg/dL and in males by 20.0 ± 17.3mg/dL in the diet-plus-exercise group in comparison with the control group. However, the change in LDL-C in the diet-only group was not significantly different to the control group.
Varady and Jones The reviewers reviewed the cholesterol-lowering effects of low-saturated-fat diets combined with exercise, and nutritional supplementation (including fish oil, oat bran, or plant sterols) combined with exercise, for the treatment of dyslipidemia. The reviewers reported that low-saturated-fat diets combined with exercise lowered total cholesterol by 7 – 18%, LDL-C by 7 – 15%, and triglyceride concentrations by 4 – 18%, while increasing HDL-C levels by 5 – 14%. They reported that nutritional supplements combined with exercise decreased by 8 – 26%, LDL-C by 8 – 30%, and triglyceride concentrations by 12 – 39%, while increasing HDL-C levels by 2 – 8%.
Kelley and Kelley The reviewers performed a meta-analysis to assess the effects of aerobic exercise on non-HDL-C in children and adolescents. The reviewers located 12 randomized controlled trials for which the data was available for inclusion within their meta-analysis. The reviewers reported that aerobic exercise displayed a non-statistically significant reduction of 0.61% in non-HDL-C. They therefore concluded that aerobic exercise does not reduce non-HDL-C in children and adolescents.
Kelley et al. The reviewers performed a meta-analysis to assess the effects of aerobic exercise on total cholesterol, LDL-C and HDL-C in female adults. The reviewers located 41 randomized controlled trials for which the data was available for inclusion within their meta-analysis. The reviewers found that aerobic exercise led to a statistically significant decrease in triglycerides of approximately 5%, a statistically significant reduction in total cholesterol of approximately 2%, a statistically significant increase in HDL-C of approximately 3%, and a statistically significant reduction in LDL-C of approximately 3%.
Kelley and Kelley The reviewers performed a meta-analysis to assess the effects of aerobic exercise on total cholesterol, LDL-C and HDL-C in male adults. The reviewers located 49 randomized controlled trials for which the data was available for inclusion within their meta-analysis. The reviewers found that aerobic exercise led to a statistically significant decrease in triglycerides of approximately 9%, a statistically significant reduction in total cholesterol of approximately 2%, a statistically significant increase in HDL-C of approximately 3%, and a trend towards a statistically significant reduction in LDL-C of approximately 2%.
Kelley et al. The reviewers performed a meta-analysis to assess the effects of aerobic exercise on total cholesterol, LDL-C and HDL-C in elderly adults aged >50 years. The reviewers located 22 randomized controlled trials for which the data was available for inclusion within their meta-analysis. The reviewers found that aerobic exercise led to a reduction of 3.3 ± 1.7mg/dL in total cholesterol, a mean increase of 2.5 ± 1.0mg/dL in HDL-C, a mean reduction of 3.9 ± 1.9mg/dL in LDL-C and a mean reduction of 7.0 ± 3.6mg/dL in triglycerides. However, after adjustments, the researchers concluded that the changes in HDL-C and the ratio of total cholesterol to HDL-C were statistically significant.
Kelley et al. The reviewers performed a meta-analysis to assess the effects of walking on non-HDL-C in adults. The reviewers located 22 randomized controlled trials for which the data was available for inclusion within their meta-analysis. The reviewers found that walking led to a statistically significant decrease in non-HDL-C of approximately 4%, which they viewed as clinically important.
Miller et al. The reviewers assessed the effects of regular exercise for the prevention of coronary artery disease. The reviewers observed that epidemiological studies have found that a physically inactive life-style is associated with twice the risk of developing coronary artery disease. Additionally, they note that in meta-analyses of studies of cardiac rehabilitation, those individuals who partake in rehabilitation have a reduced risk of death from coronary artery disease of 20 – 25% compared to those who do not. The reviewers observed that exercise leads to decreases in total and LDL-C cholesterol of 5 – 10 mg/dL and increases in HDL-C of 2 mg/dL.
Hanefeld et al. The reviewers assessed the effects of different types of physical training on atherogenic lipoprotein fractions in different populations. The reviewers observed that depending on the underlying metabolic abnormality, a different response to endurance training is observed. The reviewers conclude that physical training is particularly effective for lowering hypertriglyceridemia and for increasing HDL-C levels.
Durstine et al. The reviewers assessed the literature in respect of exercise training for altering total cholesterol, HDL-C and LDL-C levels. The reviewers concluded that total cholesterol nor LDL-C change only infrequently as a result of exercise training in either men or women, as only 1 in 4 studies observe a significant reduction in these variables following exercise. Where a reduction is observed, the reviewers note that they are similar between males and females and reductions in total cholesterol range from 7 – 27 mg/dL, or 4 – 20%, while LDL-C reductions range from 6 – 28 mg/dL or 5 to 19%. However, on the other hand, the reviewers observe that increases in HDL-C are frequently observed with moderate exercise training programs of >1200 kcal per week in males and >1000kcal per week in females.

Based on these studies and reviews, it appears that exercise is effective for reducing both total cholesterol and LDL-C while increasing HDL-C in healthy individuals.

Does exercise improve cholesterol levels in hypercholesterolemic people?

A number of exercise interventions have been performed to assess the effects of general exercise, physical activity or aerobic exercise on cholesterol levels in hypercholesterolemic individuals. The findings of these studies are shown in the table below:

Study Method Finding
Wu et al. The researchers assessed the effects of a community-based health promotion program targeting 60 individuals in northern Taiwan with hypertension and hypercholesterolemia. The health promotion program made use of various resources, including a DVD, a self-care booklet, group support (exercise and counseling sessions) and telephone follow up. The researchers observed a significant decrease in waist circumference and HDL-C levels at the point of the 6-month follow up along with significant increases in physical activity and sit-ups performance.
Coen et al. The researchers assessed the effects of statin treatment and exercise training on lipid profiles in 31 hypercholesterolemic and physically inactive subjects. The researchers randomly allocated the subjects to either a control group, a rosuvastatin group or a combined rosuvastatin and exercise group. The exercise training comprised a combined endurance and resistance training program performed 3 days per week for 20 weeks. The researchers found that total cholesterol, LDL-C and oxidized LDL-C were significantly lower in the combined and rosuvastatin groups after the intervention. They also found that oxidized LDL-C was significantly lower in the combined group after the intervention in comparison with the rosuvastatin group.
Coghill and Cooper The researchers assessed whether a home-based physical activity program along current guidelines improved the lipid profile of 67 hypercholesterolemic males from Bristol, England. The researchers randomly allocated the subjects to either 12 weeks of brisk walking or to a control group. The researchers reported that the walking intervention led to a trend towards a statistically significant increase in HDL-C of 0.07 mmol/L and a trend towards a statistically significant reduction in triglycerides of 0.30 mmol/L.
Varady et al. The researchers assessed the effects of exercise, plant sterols and the combination of exercise and plant sterols on cholesterol levels in 84 previously sedentary, hypercholesterolemic subjects. The researchers randomly allocated the subjects to 1 of 4 interventions: plant sterols combined with exercise, plant sterols, exercise, or control. The researchers found that in the combined group, total cholesterol and triglyceride levels decreased by 7.7% and 11.8%, respectively, while HDL-C levels increased by 7.5% in the combination group. They also reported that LDL-C levels decreased by 0.30 mmol/L in the combined group.
Varady et al. The researchers assessed the effects of a 24-week weight-loss intervention combining a low-fat diet with moderate endurance training (>40 minutes moderate-intensity training for 3 times per week), on LDL particle size and distribution in 30 obese, hypercholesterolemic females. The researchers reported that serum total cholesterol, LDL-C and triglyceride concentrations decreased by 8.9%, 7.5% and 27.1%, respectively, while HDL-C concentrations increased by 9.9%.
Croce et al. The researchers assessed the effects of changes in dietary habits, alone or in association with regular physical activity, on 38 hypercholesterolemic patients. The researchers randomly allocated the subjects to either a diet group or a diet plus exercise group for a 4-week intervention. The exercise group performed daily aerobic exercise for 30 minutes (including 5-minute warm-up and 5-minute cool-down periods during each session) on a bicycle ergometer at 50 – 70% of their maximum heart rate. The researchers reported that LDL-C levels significantly decreased after 4 weeks in both groups but the reduction was more marked in the combined diet  plus exercise group. The researchers found that serum HDL-C levels increased and serum triglyceride concentrations decreased in both groups.
Crouse et al. The researchers assessed the effects of exercise at two different intensities on blood lipids and apolipoproteins in 26 hypercholesterolemic males. The subjects trained 3 times per week for 24 weeks at either high- (80% of VO2-max) or moderate- (50% of VO2-max) intensity. The researchers reported that total cholesterol was lower after training than before training but there was no difference between the high- and moderate-intensity groups.
Shorey et al. The researchers assessed the effects diet and exercise on serum lipids in young males with varying degrees of hyperlipidemia. The researchers found that those subjects with elevated levels of both cholesterol and triglyceride were less amenable to change than those with a single hyperlipidemia. The researchers also found that for certain risk factors, there was a beneficial effect of exercise in addition to diet in respect of serum lipids.
Kelley et al. The reviewers performed a meta-analysis to assess the effects of aerobic exercise on total cholesterol, LDL-C and HDL-C in adults with cardiovascular disease. The reviewers located 10 randomized controlled trials for which the data was available for inclusion within their meta-analysis. The reviewers found that aerobic exercise led to a statistically significant reduction of approximately 11% in triglycerides, a non-statistically significant reduction of approximately 4% in total cholesterol, a statistically significant increase in HDLD-C of approximately 9%, and a non-statistically significant reduction in LDL-C of approximately 5%, although this difference became significant when one study was removed.

Based on these studies and reviews, it appears that exercise is effective for reducing hypercholesterolemia in hypercholesterolemic people and is able to decrease both total cholesterol and LDL-C while increasing HDL-C.


Does exercise improve cholesterol levels in obese and overweight people?

A number of exercise interventions have been performed to assess the effects of general exercise, physical activity or aerobic exercise on cholesterol levels in obese and overweight individuals. The findings of these studies are shown in the table below:

Study Method Finding
Lee et al. The researchers wanted to assess the effects of exercise on anthropometric, metabolic, and cardiovascular variables in 54 obese children. The researchers allocated the children into 3 groups: an aerobic exercise group, a combined exercise group and a control group for a 10-week program. The combined exercise program comprised a warm-up, main exercise and cool-down. The warm-up comprised stretching and jogging for 5 minutes. The main exercise comprised body weight exercises, circuit training and aerobic exercise. The cool-down comprised stretching for 5 minutes. The aerobic exercise also comprised a warm-up, main exercise and cool-down. The warm-up and the cool-down phases were the same as for the combined exercise program but the main exercise phase comprised activities such as soccer, basketball, football, baseball, hockey, badminton and rope skipping. The researchers reported that LDL-C, waist circumference and systolic blood pressure all decreased significantly in the aerobic exercise group in comparison with the control group. LDL-C decreased from 116.07 ± 28.08 mg/dL to 103.73± 27.48 mg/dL. They also reported that waist circumference and systolic blood pressure decreased significantly in the combined exercise group in comparison with the control group. LDL-C decreased from 115.42 ± 14.13 mg/dL to 105.68 ± 16.43 mg/dL.
Andersen et al. The researchers assessed the effects of weight-loss as a result of various diet and exercise programs on serum lipids and lipoproteins in 66 obese women over a 48-week weight-loss intervention, including an initial 8-week period of a very-low-calorie diet. The researchers reported that overall, weight reduced by 11.1% (10.6kg) during the first 8 weeks, during which time total cholesterol fell 0.95 mmol/L (15.7%) and LDL-C fell 0.59mmol/L.
Varady et al. The researchers assessed the effects of a 24-week weight-loss intervention combining a low-fat diet with moderate endurance training (>40 minutes moderate-intensity training for 3 times per week), on LDL particle size and distribution in 30 obese, hypercholesterolemic females. The researchers reported that serum total cholesterol, LDL-C and triglyceride concentrations decreased by 8.9%, 7.5% and 27.1%, respectively, while HDL-C concentrations increased by 9.9%.
Kelley et al. The reviewers performed a meta-analysis to assess the effects of aerobic exercise on total cholesterol, LDL-C and HDL-C in obese and overweight adults. The reviewers located 13 randomized controlled trials for which the data was available for inclusion within their meta-analysis. The reviewers found that aerobic exercise led to a statistically significant reduction in triglycerides of approximately 11%, a statistically significant reduction in total cholesterol of 2%, a statistically non-significant increase in HDL-C of approximately 3% and as a statistically non-significant reduction in LDL-C of approximately 0.3%.

Based on these studies, it appears that general exercise is effective for reducing hypercholesterolemia in obese and overweight people and is able to decrease both total cholesterol and LDL-C while increasing HDL-C.

Does exercise improve cholesterol levels in diseased populations?

A number of exercise interventions have been performed to assess the effects of general exercise, physical activity or aerobic exercise on hypercholesterolemia in other diseased populations. The findings of these studies are shown in the table below:

Study Method Finding
Painter et al. The researchers assessed the effects of exercise on hypercholesterolemia during the first year after renal transplantation in 96 transplant recipients. The researchers randomly allocated the subjects 1 of 2 groups, 1 month post-transplantation: an exercise group and a usual care group. The researchers reported that all patients displayed increases in total cholesterol, HDL-C and body mass index (BMI) over time. However, there was a non-statistically significant trend toward greater improvement in HDL-C levels in the exercise group and significantly more patients in the exercise group moved out of the high-risk category for total cholesterol to HDL-C ratio.
Birk et al. The researchers assessed the effects of 12 months of aerobic exercise on blood lipid and lipoprotein concentrations in 5 men with advanced HIV-1 infection. The researchers reported that the aerobic exercise program did not alter total cholesterol, HDL-C or triglycerides.
Gayda et al. The researchers assessed the effects of long-term cardiac rehabilitation and exercise training programs in 59 patients with metabolic syndrome and coronary heart disease and 81 patients with metabolic syndrome without coronary heart disease. The exercise training was performed twice per week for a mean duration of one year. In the metabolic syndrome patients without coronary heart disease, LDL-C reduced from 3.43 ± 1.06 to 3.31 ± 1.05mmol/L while total cholesterol reduced from 5.87 ± 1.20 to 4.94 ± 1.40mmol/L. Similarly, in the patients with metabolic syndrome and coronary heart disease LDL-C reduced from 3.17 ± 1.26 to 2.88 ± 1.02mmol/L while total cholesterol reduced from 5.44 ± 1.57mmol/L to 4.83 ± 1.56mmol/L.
Hayashino et al. The reviewers carried out a systematic review to assess the effect of supervised exercise interventions on lipid profiles and blood pressure control in people with diabetes. They found 42 randomized controlled trials and included these in a meta-analysis. The reviewers found that structured exercise was associated with an increase in HDL-C of 0.04 mmol/L and decrease in LDL-C of 0.16 mmol/L although there was some heterogeneity, which was partially explained by age, dietary co-intervention and the duration and intensity of the exercise. The reviewers therefore concluded that supervised exercise is effective in lowering LDL-C and elevating HDL-C levels in people with diabetes. They advised that physicians should recommend exercise for adult patients with diabetes where it is safe to do so.
Kelley and Kelley The reviewers performed a meta-analysis to assess the effects of aerobic exercise on total cholesterol, LDL-C and HDL-C in adults with diabetes. The reviewers located 7 randomized controlled trials for which the data was available for inclusion within their meta-analysis. The reviewers found that aerobic exercise led to a statistically significant reduction in LDL-C of approximately 5% and non-statistically significant reductions in total cholesterol of 2% and in HDL-C of 2%. Since previous studies have reported that every 1% reduction in LDL-C reduces coronary heart disease risk by about 1.7%, the reviewers suggested that the 5% reduction in LDL-C is clinically important for this population, as it would translate to a 8.5% reduction in coronary heart disease risk.

Based on these studies, it appears that general exercise can help reduce total cholesterol and LDL-C in patients with the metabolic syndrome and with type II diabetes but not with HIV.


Does resistance-training improve cholesterol levels?

A number of exercise interventions have been performed to assess the effects of resistance training on hypercholesterolemia in various different populations, as shown in the table below:

Study Method Finding
García-Unciti et al. The researchers assessed the effects of diets with differing levels of protein (high vs. low) and the effects of progressive resistance training program on body composition and lipoprotein profile in 25, sedentary, hypercholesterolemic, obese females aged 40 – 60 years over a 16-week intervention period. The control group for exercise performed only habitual while the progressive resistance training group performed supervised whole-body resistance training, twice a week. The training program included bilateral leg press, bilateral knee extension and bench-press machine exercises among others. For the first 8 weeks of the training intervention the subjects trained with loads of 50 – 70% of 1RM and in the second 8 weeks, they used loads of 70 – 80% of 1RM. The researchers observed that both resistance training groups (low protein and high protein), displayed significant reductions in HDL-C and total cholesterol (11.5% and 13.6%, respectively). Additionally, they reported that LDL-C concentrations were also affected by resistance training (displaying a 13.8% reduction across both resistance training groups), although there was also a significant difference between groups in that a lower protein diet in combination with resistance training displayed a significantly greater reduction in LDL-C than a higher protein diet with the same resistance training program.
Kelley and Kelley The reviewers performed a meta-analysis to assess the effects of resistance training on total cholesterol, LDL-C and HDL-C in male adults. The reviewers located 29 randomized controlled trials for which the data was available for inclusion within their meta-analysis. The reviewers found that resistance training led to a statistically significant reduction in triglycerides of approximately 6.4%, a statistically significant reduction in total cholesterol of approximately 2.7%, a statistically significant reduction in LDL-C of approximately 4.6%, and a trend towards a statistically significant increase in HDL-C of approximately 1.4%.

Based on these studies, it appears that resistance training is effective for reducing hypercholesterolemia and is able to decrease total cholesterol, triglycerides and LDL-C.


Conclusions

Based on the above research studies, reviews and analysis, we can conclude the following key points in relation to exercise, physical activity and hypercholesterolemia:

Area Conclusion
Hypercholesterolemia and all-cause mortality in the general population It seems likely that reducing low-density lipoprotein cholesterol (LDL-C) does reduce the risk of coronary heart disease events and coronary heart disease mortality in both males and females, and possibly also all-cause mortality in males (although the literature is conflicting) but not females.
Hypercholesterolemia and all-cause mortality in elderly people It seems likely that reducing serum levels of low-density lipoprotein cholesterol (LDL-C) does not reduce the risk of coronary heart disease events, coronary heart disease mortality and all-cause mortality in elderly people. Rather, it may in fact increase the risk of death.
Risk factors for hypercholesterolemia It appears that physical activity (including walking and running) and weight-loss or control programs are associated with a lower risk of hypercholesterolemia while being overweight or obese is associated with an increased risk of hypercholesterolemia.
Effects of exercise on hypercholesterolemia It appears that general exercise is effective for reducing hypercholesterolemia and is able to decrease both total cholesterol and LDL-C while increasing HDL-C in healthy, obese and overweight, hypercholesterolemic and many other diseased populations.

In summary, it seems that reducing low-density lipoprotein cholesterol (LDL-C) does reduce the risk of coronary heart disease events and coronary heart disease mortality in both males and females, and possibly also all-cause mortality in males (although the literature is conflicting) but not females. However, general exercise is effective for reducing hypercholesterolemia and may be able to decrease both total cholesterol and LDL-C while increasing HDL-C in healthy, obese and overweight, hypercholesterolemic and many other diseased populations.


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