From the National Health Insurance Service Cohort, 23, individuals diagnosed with T2D from to were followed-up for non-fatal CVD incidence through Two measurements of TC, 2 years before and after T2D diagnosis, were classified into 3 levels low, middle, high to define changes in cholesterol levels.

Subgroup analyses were performed by use of lipid-lowering drugs. Compared with low—low, aHR of CVD was 1. Compared with middle—middle, aHR of CVD was 1. Compared with high—high, aHR of CVD was 0.

The associations were observed regardless of use of lipid-lowering drugs. For diabetic patients, management of TC levels may be important to lower CVD risk. Cardiovascular disease CVD is the leading cause of death globally 1 , 2. The World Health Organization WHO predicts that more than 23 million people will die of CVD by 2.

A major gateway disease to CVD is type 2 diabetes T2D 3. In a meta-analysis of 30 cohort studies, diabetic patients had 1. With the worldwide prevalence of T2D reaching 9. One strong risk factor for CVD in a healthy population is hypercholesterolemia 6 , 7 , and its adverse effect on CVD might be more evident among individuals with underlying metabolic disease like T2D.

Thus, diabetic patients may be more vulnerable to the adverse effect of hypercholesterolemia on CVD risk of T2D. However, diagnosis of T2D often leads to positive lifestyle modification, which helps lower the risk of hypercholesterolemia and CVD.

The net effect of these divergent factors on cholesterol levels is captured in changes in cholesterol levels around the diagnosis of T2D. Despite that an estimated Therefore, we investigated how changes in total cholesterol TC levels from pre- to post-diagnosis of T2D are associated with subsequent CVD risk, accounting for the use of lipid-lowering drugs including statin, fibrate, and ezetimibe.

Among 23, participants, 9. In Table 1 , compared to patients with constant TC levels before and after T2D diagnosis, patients whose TC levels increased after T2D diagnosis tended to have higher BMI, lower engagement in physical activity, higher blood pressure, higher fasting serum glucose, higher aspartate transaminase AST , higher alanine transaminase ALT , higher gamma-GTP, and higher use of lipid-lowering drugs.

In Table 2 , increases in TC levels after T2D diagnosis were generally associated with increased CVD risk, while decreases in TC levels after T2D diagnosis were generally associated with decreased CVD risk.

Among diabetic patients who were non-users of lipid-lowering drugs, CVD risk increased for low—middle aHR 1. Among diabetic patients who were users of lipid-lowering drugs, CVD risk increased in low—middle aHR 1.

The aHR of CVD in diabetic patients comparing middle—low vs. middle—middle TC levels was 0. Among diabetic patients who were non-users of lipid-lowering drugs, CVD risk decreased in high—middle aHR 0. Among diabetics who were users of lipid-lowering drugs, CVD risk decreased in high—middle aHR 0.

For CHD and stroke risk in relation to TC changes, the associations were consistent with the results of CVD in overall diabetic patients, but heterogeneous results emerged in subgroup analysis by use of lipid-lowering drugs Table 2.

For CHD, an increased risk associated with elevated TC was evident in users of lipid-lowering drugs, with aHR comparing low—middle vs.

low—low being 1. This heterogeneous results by use of lipid-lowering drugs were consistently observed in the results for low—high vs. low—low, albeit not statistically significant due to small number of cases.

In contrast, a decreased risk associated with lowered TC was evident in non-users of lipid-lowering drugs, with aHR comparing high—middle vs. high—high being 0. In contrast, for stroke, an increased risk associated with elevated TC was evident in non-users of lipid-lowering drugs, with aHR comparing low—high vs.

low—low being 3. high—high was suggestive regardless of use of lipid-lowering drugs. For CVD, CHD, stroke outcomes, additional analyses were performed. In sensitivity analyses conducted among statin users, the results did not change materially compared to the results among users of any lipid-lowering drugs Supplementary Table 1.

In subgroup analyses conducted among participants with information on HDL-C, LDL-C, and TG levels, changes in HDL-C and TG levels after T2D diagnosis were not associated with CVD risk.

Table 3 presents the results by subtypes of CHD and stroke. While some of the results were statistically unreliable due to a small number of cases, the overall pattern of increasing risk with increasing TC levels and decreasing risk with decreasing TC levels after T2D diagnosis was more evident for angina, MI, and ischemic stroke, all of which are of ischemic origin.

For examples, compared with low—low, aHR for low—middle was 1. Table 4 shows factors indicative of TC reductions among diabetic patients who were non-users of lipid-lowering drugs. For any of high or middle TC levels before T2D diagnosis, male sex and low fasting glucose levels after T2D diagnosis were associated with approximately 1.

On the contrary, Table 5 shows factors indicative of non-improvements in TC levels among diabetic patients who were lipid-lowering drugs users. Overall, female sex, high blood pressure, and high fasting glucose level after T2D diagnosis were suggestive of lipid-lowering drugs resistance, with OR of as non-decreasing or even increasing TC levels ranging from 1.

Supplementary 3 and 4 , we performed same analysis of Tables 4 and 5 , respectively and lipid-lowering drugs were substituted with statins. The results replaced by statin were similar to those of lipid-lowering drugs.

In patients with T2D, increases in TC level from pre- to post-diagnosis period were associated with elevated CVD risks, while decreases in TC levels were associated with lowered CVD risks.

These trends were observed for CVD outcome regardless of use of lipid-lowering drugs and for both CHD and stroke, and more apparent in ischemic diseases than hemorrhagic diseases. Of note, the results for CHD and stroke became heterogeneous when stratified by use of lipid-lowering drugs.

In diabetic patients, male sex and low fasting glucose levels were associated with TC reduction without use of lipid-lowering drugs, while female sex, high fasting glucose level, and high blood pressure were associated with non-improvements in TC levels despite use of lipid-lowering drugs.

In generally healthy populations, an elevated cholesterol level in the blood is an established risk factor of CVD 10 , 11 , 12 , Excessive cholesterols, particularly LDL-C, build up in the walls of arteries, forming plaques that narrow or block the arteries that feed the heart or brain 14 , Alternatively, the atherosclerotic plaque could be ruptured and the resulting blood clots could travel through vessels and block small vessels that flow to the heart or brain 16 , These blockages deprive the heart or brain tissues of blood and oxygen, leading to tissue damage or death 16 , Compared to non-diabetic individuals, patients with T2D are at higher risk for hypercholesterolemia, because insulin resistance and ensuing increases in fatty acids flux to the liver lead to an increased secretion of very low density lipoprotein, which converts to LDL in the bloodstream Increases in insulin levels are also positively correlated with increases in gene expression of 3-hydroxymethylglutaryl-CoA reductase HMGR , a rate-limiting enzyme of the cholesterol biosynthetic pathway Furthermore, T2D patients often have smaller LDL particles, which are more atherogenic than normal size LDL In a previous study conducted among healthy adults aged 20—39 years from this cohort, an increase in TC levels from low to high was associated with 1.

Nevertheless, we cannot rule out the possibility that the stronger association observed in our study could be due to the older age of the diabetic patients 59—61 years of age rather than the interplay of TC increase and diabetes. One study followed T2D patients to examine the relationship between cholesterol level at T2D diagnosis and the risk of MI and stroke while considering statin use 8.

Of note, our study, which investigated change in TC levels from pre- to post-diagnosis of T2D rather than TC levels at a point in time, performed subgroup analyses by use of lipid-lowering drugs. We observed that a decrease in TC after T2D diagnosis was more evidently associated with a lowered CHD risk among non-users of lipid-lowering drugs, while the decrease was associated with an elevated stroke risk among users of lipid-lowering drugs.

Our results suggest that not only changes in TC levels, but also how the changes were induced might influence the disease risk.

When cholesterol reduction was achieved through lifestyle modifications alone, because healthy diet and lifestyle affect a broad range of metabolic profiles accompanying LDL reduction, HDL increase, and improved glucose control 21 , 22 , 23 , all of which help reduce CHD risk.

In contrast, when cholesterol reduction was achieved via lipid-lowering drugs, its effect is rather specific to LDL reduction 24 and emerging evidence suggests that lipid-lowering drugs might increase blood glucose levels in pre-diabetic or diabetic people Indeed, in our study, non-users of lipid-lowering drugs who managed to reduce TC levels after T2D diagnosis were associated with lower fasting serum glucose levels, whereas users of lipid-lowering drugs who failed to reduce TC levels were associated with higher fasting serum glucose levels.

Furthermore, users of lipid-lowering drugs, despite their unhealthy eating habits, might still managed to control their cholesterol levels due to lipid-lowering drugs effect. For instance, statin has shown to reduce blood pressure 26 , which appears more protective against stroke than against heart disease This explanation is consistent with our observation that among users of lipid-lowering drugs, an increased cholesterol level was more evidently associated with an elevated CHD risk than with stroke.

In our analyses by CVD subtypes, associations with TC changes were more evident for advanced ischemic diseases such as angina and MI than chronic IHD, and for ischemic stroke than hemorrhagic stroke.

These results are consistent with the mechanism that high cholesterol levels, by forming atherosclerotic plaque and blocking arterial blood vessels, elevates CVD risks. For ischemic vs. Of note, the largest proportion of total body cholesterol is contained in the brain 29 and cholesterol is the major component of myelin membranes While a low cholesterol concentration in the brain could lead to membrane fragility, making the brain vulnerable to hemorrhagic stroke 31 , the brain cholesterol is controlled by local synthesis and independent of circulating cholesterol levels due to the action of the blood—brain barrier Thus, an association between cholesterol levels in the blood and hemorrhagic stroke appears biologically less plausible.

Nevertheless, in previous studies of generally healthy populations, high TC levels in the blood were associated with an increased ischemic stroke risk, but with a decreased hemorrhagic stroke 33 , Women were more likely to experience increases or non-decreases in TC levels despite use of lipid-lowering drugs.

One potential explanation relates to estrogens, which have been suggested to protect women from CVD CVD is less prevalent in premenopausal women than men and women experience an increased rate of CVD after the onset of menopause, with estrogen replacement therapy resulting in improved blood lipid profiles in postmenopausal women Although the mechanism underlying cholesterol-lowering effect of estrogen remains elusive, estrogens have been reported to increase cholesterol clearance via increasing LDL receptors and to decrease cholesterol synthesis via inhibiting HMGR In an experimental study, HMGR activity and expression were lower in female rats and in β -estradiol treated male rats than in male rats Given an already decreased activity HMGR by estrogens in women, stains that inhibit HMGR to reduce LDL are less likely to benefit women than men.

Similarly, under the presence of cholesterol-lowering effect of estrogen in women, the beneficial effects of lifestyle modification on cholesterol levels are less likely to manifest in women than in men, which was observed in our study. Our study has several strengths. To our knowledge, this is the first study that examined changes in TC levels from pre- to post-diagnosis among diabetic patients in relation to subsequent CVD risk.

By analyzing changes in TC levels rather than the level at one time point, our study mimics an intervention study on cholesterol levels and disease risk, which better elucidates causality of the relationship.

Yet, several limitations deserve attention. First, inaccuracy inherent in NHIS claims data may compromise the validity of our findings. To address this limitation, we defined our cohort of diabetic patients based on the combination of ICD codes, hospitalization record, and prescription of anti-diabetic medication.

Second, since information on HDL-C and LDL-C was only recently introduced in the NHIS-HEALS database, we could not conduct our study by subtypes of cholesterols.

As changes in TC levels could be driven by HDL-C or LDL-C, analysis using TC might have attenuated the true relationships between cholesterol change and CVD risk among diabetic patients. However, because the major benefit of lipid-lowering drugs is lowering LDL-C, our subgroup analysis by among users of lipid-lowering drugs helps understand the effect of LDL-C reduction on CVD risk among diabetic patients.

Finally, recruitment period of diabetic patients in our study spans a long period from up to Over this time period, the prescription of metformin was increasing while that of sulfonylurea was decreasing in treating diabetic patients 40 and use of different anti-diabetic medication could have differential effect on cholesterol level and CVD risk.

While we adjusted for type of anti-diabetic medication use during two years after T2D diagnosis, residual confounding by change in anti-diabetic medication use over time cannot be completely ruled out.

In conclusion, among diabetic patients, regardless of use of lipid-lowering drugs, increases in TC level from pre- to post-diagnosis period were associated with elevated CVD risks, while the decreases were associated with reduces CVD risks.

Management of TC level among diabetic patients may be of an important clinical goal to prevent CVD. The National Health Insurance Service NHIS in Korea is the mandatory health insurance system that achieved universal coverage of the population since The NHIS has provided the general health screening programs biennially The cohort included , participants aged 40—79 years in and followed them through The cohort had information regarding demographic and socioeconomic factors, medical history, bioclinical laboratory results, and lifestyle factors.

From the NHIS-HEALS, we selected a total of 27, participants who were diagnosed with T2D between and Diabetic patients were identified based on International Classification of Diseases 10th Revision ICD codes E11, E12, E14 and prescription history of anti-diabetic medication.

Among them, we excluded patients who were diagnosed with CVD or died before the start of study follow-up i. Based on these two measurements, changes in TC levels from pre- to post-diagnosis of T2D were divided into 9 groups: low—low, low—middle, low—high, middle—low, middle—middle, middle—high, high—low, high—middle, and high—high.

The time frame was between the date of T2D diagnosis and the date when the follow-up started i. Covariates included in the multivariable analysis were as follows: age, sex, socioeconomic status, body mass index BMI , smoking status, alcohol consumption, physical activity, systolic blood pressure, fasting serum glucose, history of anti-diabetic medication, and use of lipid-lowering drugs after T2D diagnosis.

Users of lipid-lowering drugs were defined as those who used all kind of lipid-lowering drugs such as statin, fibrate, ezetimibe, and non-users were as those who did not use any kind of lipid-lowering drugs.

Statin users were defined as those who used statin alone or in combination. The primary outcome was non-fatal CVD incidence, defined as two or more days of hospitalization due to CVD as indicated by ICD codes I20—I25, I60—I69 The secondary outcomes were coronary heart disease CHD, I20—I25 and stroke I60—I69 incidences.

If a patient was diagnosed with both CHD and stoke, the earlier diagnosis was used as the outcome. For each pre-diagnostic TC category, the reference group included individuals staying in the same category for both pre- and post-diagnostic period e.

For every participant, the start of follow-up i. To estimate cumulative probability of non-fatal CVD incidence according to changes in TC levels from pre- to post-diagnosis of T2D, we used the Kaplan—Meier method and log-rank test.

Heterogeneity in the relationship by CVD subtypes CHD, stroke was also explored. Because lipid abnormalities are common in T2D patients, patients were often prescribed lipid-lowering drugs, which may be an important modifier of the relationship between TC change and CVD risk.

Thus, we also performed sensitivity analysis among statin users. Potential interaction between change in TC levels and use of lipid-lowering drugs was tested by adding their cross-product product term in the model and running the Wald test on it. Among individuals with high TC levels before T2D diagnosis, some managed to lower their TC levels after T2D diagnosis, which could be attributable to use of lipid-lowering drugs or lifestyle modifications.

To identify post-T2D diagnosis factors associated with TC reduction without the help of medication, we performed logistic regression to predict TC decrease e. On the contrary, among individuals on lipid-lowering drugs, despite their medication use, some failed to lower or even had elevated TC levels after T2D diagnosis.

To identify post-T2D diagnosis factors associated with ineffectiveness of lipid lowering medication, we performed logistic regression to predict TC non-decrease or increase e.

To explore whether the relationship between TC levels and CVD risk differs by 3rd factors, we performed subgroup analyses by variables selected a priori known to influence CVD risk: age, sex, BMI, smoking status, alcohol consumption, and physical activity Supplementary table 5.

All statistical analyses were conducted using SAS 9. These deposits plaques can reduce blood flow through your arteries, which can cause complications, such as:. The same heart-healthy lifestyle changes that can lower your cholesterol can help prevent you from having high cholesterol in the first place.

To help prevent high cholesterol, you can:. Our patients tell us that the quality of their interactions, our attention to detail and the efficiency of their visits mean health care like they've never experienced. See the stories of satisfied Mayo Clinic patients.

Editors note: This is a first-person account written by Kim Sidlak I was 46 years old when I had a massive heart attack. It was a Wednesday evening, June 4, It was a day I will never forget. My grandmother and mother both died from heart issues in their early fifties, so I knew heart disease ran in my family.

I had read about heart disease in women, eating healthy, staying active, and keeping…. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press.

This content does not have an English version. This content does not have an Arabic version. Overview Cholesterol is a waxy substance found in your blood. More Information Arcus senilis: A sign of high cholesterol? Request an appointment.

Thank you for subscribing! Sorry something went wrong with your subscription Please, try again in a couple of minutes Retry. Development of atherosclerosis Enlarge image Close. Development of atherosclerosis If there's too much cholesterol in the blood, the cholesterol and other substances may form deposits called plaque.

Embracing wellness following massive heart attack Editors note: This is a first-person account written by Kim Sidlak I was 46 years old when I had a massive heart attack. By Mayo Clinic Staff.

Show references Blood cholesterol. National Heart, Lung, and Blood Institute. Accessed March 10, Lipid panel. Lab Tests Online. American Association for Clinical Chemistry. Goldman L, et al. Disorders of lipid metabolism. In: Goldman-Cecil Medicine.

Elsevier; My cholesterol guide. American Heart Association. Bonow RO, et al. Lipoprotein disorders and cardiovascular disease. In: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. Ferri FF. In: Ferri's Clinical Advisor Rosenson RS, et al. Management of low density lipoprotein cholesterol LDL-C in the secondary prevention of cardiovascular disease.

Rosenson RS. Low density lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors. Tibuakuu M, et al. See our editorial policies and staff. About Cholesterol. HDL, LDL Cholesterol and Triglycerides.

Genetic Conditions. Causes of High Cholesterol. How To Get Your Cholesterol Tested. Prevention and Treatment of High Cholesterol. Cholesterol Tools and Resources. Home Health Topics Cholesterol About Cholesterol What Your Cholesterol Levels Mean.

Play without Auto-Play Play Video Text. Understanding your cholesterol levels Maintaining healthy cholesterol levels is a great way to keep your heart healthy. But first, you have to know your cholesterol numbers. The American Heart Association recommends All adults age 20 or older should have their cholesterol and other traditional risk factors checked every four to six years.

LDL bad cholesterol Since LDL is the bad kind of cholesterol, a low LDL level is considered good for your heart health. How low can I go with my LDL? Talk to your health care professional. PDF Spanish PDF Why Should I Know My LDL Cholesterol?

For more science-backed resources on nutrition, visit our dedicated hub. They also recommend a person minimize the amount of trans fat they consume. Learn more about how to lower cholesterol without medication here. High cholesterol levels do not typically cause any noticeable symptoms.

Some people with high cholesterol may develop yellowish, cholesterol-rich, deposits on their skin , which doctors call xanthomas. However, other health conditions may also cause xanthomas. Without regular testing, people may not know they have high cholesterol until they develop heart disease.

However, heart disease often does not cause noticeable symptoms either. Therefore, the CDC recommends that:. If a person wishes to find out more about their cholesterol levels and individual risk for developing heart disease, they can take with a doctor to discuss their specific situation.

Many organizations like the CDC and AHA recommend managing cholesterol levels to help reduce the risk of developing heart disease. High LDL cholesterol levels in the bloodstream may increase the risk of heart disease and cardiovascular events like stroke.

However, scientists are still investigating the relationship between cholesterol and the risk of heart disease, particularly how dietary cholesterol may affect heart health. People may want to consider modifying their diet, maintaining a moderate weight, and exercising regularly to help lower their cholesterol levels.

They can also speak with a healthcare professional about regular cholesterol level checks and their individual risk of heart disease. A person's blood cholesterol levels do matter, but research is inconclusive as to whether or not dietary cholesterol matters.

Learn more here. Natural ways to lower cholesterol include replacing trans fats and saturated fats, eating more soluble fiber, and exercising regularly. Learn more…. Tetralogy of Fallot is a group of four heart abnormalities that can develop while a fetus is in the womb.

It can affect how the blood flows in the…. New research suggests that women with a high risk strain of HPV may be at a four-time higher risk of dying from cardiovascular disease. A heart disease diet centers on fruits and vegetables, whole grains, lean meats, healthy fats, and fatty fish.

It may help reduce the risk of…. My podcast changed me Can 'biological race' explain disparities in health? Why Parkinson's research is zooming in on the gut Tools General Health Drugs A-Z Health Hubs Health Tools Find a Doctor BMI Calculators and Charts Blood Pressure Chart: Ranges and Guide Breast Cancer: Self-Examination Guide Sleep Calculator Quizzes RA Myths vs Facts Type 2 Diabetes: Managing Blood Sugar Ankylosing Spondylitis Pain: Fact or Fiction Connect About Medical News Today Who We Are Our Editorial Process Content Integrity Conscious Language Newsletters Sign Up Follow Us.

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What to know about cholesterol and heart disease. Medically reviewed by Angela M. Bell, MD, FACP — By Ben Koprowski on February 28, What is cholesterol? Links Lowering cholesterol When to see a doctor Summary People with higher cholesterol levels may have a higher risk of developing heart disease.

Cholesterol and heart disease. Nutrition resources For more science-backed resources on nutrition, visit our dedicated hub. Was this helpful? Tips for lowering cholesterol. When to see a doctor. How we reviewed this article: Sources. Medical News Today has strict sourcing guidelines and draws only from peer-reviewed studies, academic research institutions, and medical journals and associations.

We avoid using tertiary references. We link primary sources — including studies, scientific references, and statistics — within each article and also list them in the resources section at the bottom of our articles. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.

High cholesterol can cause a dangerous accumulation of cholesterol and other deposits on the walls of your arteries atherosclerosis.

These deposits plaques can reduce blood flow through your arteries, which can cause complications, such as:. The same heart-healthy lifestyle changes that can lower your cholesterol can help prevent you from having high cholesterol in the first place.

To help prevent high cholesterol, you can:. Our patients tell us that the quality of their interactions, our attention to detail and the efficiency of their visits mean health care like they've never experienced.

See the stories of satisfied Mayo Clinic patients. Editors note: This is a first-person account written by Kim Sidlak I was 46 years old when I had a massive heart attack.

It was a Wednesday evening, June 4, It was a day I will never forget. My grandmother and mother both died from heart issues in their early fifties, so I knew heart disease ran in my family.

I had read about heart disease in women, eating healthy, staying active, and keeping…. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press.

This content does not have an English version. This content does not have an Arabic version. Overview Cholesterol is a waxy substance found in your blood.

More Information Arcus senilis: A sign of high cholesterol? Request an appointment. Thank you for subscribing! Sorry something went wrong with your subscription Please, try again in a couple of minutes Retry.

Development of atherosclerosis Enlarge image Close. Development of atherosclerosis If there's too much cholesterol in the blood, the cholesterol and other substances may form deposits called plaque.

Embracing wellness following massive heart attack Editors note: This is a first-person account written by Kim Sidlak I was 46 years old when I had a massive heart attack. By Mayo Clinic Staff.

Show references Blood cholesterol. National Heart, Lung, and Blood Institute. Accessed March 10, Lipid panel. Lab Tests Online. American Association for Clinical Chemistry. Goldman L, et al. Disorders of lipid metabolism.

In: Goldman-Cecil Medicine. Elsevier; My cholesterol guide. American Heart Association. Bonow RO, et al. Lipoprotein disorders and cardiovascular disease. In: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine.

Ferri FF. In: Ferri's Clinical Advisor Rosenson RS, et al. Management of low density lipoprotein cholesterol LDL-C in the secondary prevention of cardiovascular disease.

Rosenson RS. Low density lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors. Tibuakuu M, et al. Bempedoic acid for LDL-C lowering: What do we know? American College of Cardiology. De Ferranti SD, et al. Dyslipidemia in children: Management. Cholesterol management at a glance.

National Center for Complementary and Integrative Health. Accessed April 1, Related Arcus senilis: A sign of high cholesterol?

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