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Cholesterol - Complications

Description

An in-depth report on the diagnosis, treatment, and prevention of unhealthy cholesterol levels.

Alternative Names

Hypercholesterolemia; LDL; HDL; Triglycerides

Complications:

Heart Disease

Atherosclerosis is a common disorder of the arteries. Fat, cholesterol, and other substances collect in the walls of arteries. Larger accumulations are called atheromas or plaque and can damage artery walls and block blood flow. Severely restricted blood flow in the heart muscle leads to symptoms such as chest pain.

Unhealthy cholesterol, particularly low-density lipoprotein (LDL) cholesterol, forms a fatty substance called plaque, which builds up on the arterial walls of the heart. Smaller plaques remain soft, but older, larger plaques tend to develop fibrous caps with calcium deposits.

Developmental process of atherosclerosis
Click the icon to see an image of the developmental process of atherosclerosis.

The long-term result is atherosclerosis, commonly called hardening of the arteries. The heart is endangered in two ways by this process:

Eventually these calcified and inelastic arteries become narrower (a condition known as stenosis). As this process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart. This condition leads to angina (chest pain) and, in severe cases, to heart attack.

Acute MI
Click the icon to see an image of a heart attack.

Smaller unstable plaques may rupture, triggering the formation blood clots on their surface. The blood clots block the arteries and are important causes of heart attack.

This process is accelerated and enhanced by other risk factors, including high blood pressure, smoking, obesity, diabetes, and a sedentary lifestyle. When more than one of these risk factors is present, the risk is compounded.

Coronary Artery Disease. The end result of atherosclerosis is coronary artery disease. Coronary artery disease, commonly known as heart disease, is the leading cause of death in the U.S.

Studies consistently report a higher risk for death from heart disease with high total cholesterol levels (200 mg/dL and higher). The higher the cholesterol, the greater the risk. On average, every time a person's total cholesterol level drops by a point, the risk of heart disease drops by 2%. [For more information, see In-Depth Reports #03: Coronary artery disease.]

Peripheral Artery Disease

Peripheral artery disease (PAD) is caused by the buildup of plaque in the feet, legs, hands, and arms. It most often occurs in the legs. PAD is associated with atherosclerosis. The risk for PAD increases by 5 - 10% with every 10 mg/dL increase in total cholesterol levels. Lower levels of HDL and high triglyceride levels also increase the risk for PAD. [For more information, see In-Depth Report #102: Peripheral artery disease.]

Stroke

Having adequate levels of HDL may be the most important lipid-related factor for preventing ischemic stroke, a type of stroke caused by blockage of the carotid arteries that carry blood to the brain. HDL may even reduce the risk for hemorrhagic stroke, a less common type of stroke caused by bleeding in the brain that is associated with low overall cholesterol levels.

The build-up of plaque in the internal carotid artery may lead to narrowing and irregularity of the artery's lumen, preventing proper blood flow to the brain. More commonly, as the narrowing worsens, pieces of plaque in the internal carotid artery can break free, travel to the brain, and block blood vessels that supply blood to the brain. This leads to stroke, with possible paralysis or other deficits.

Atherosclerosis of internal carotid artery

The effects of high total cholesterol and LDL levels on ischemic stroke are less clear. Some research suggests that the risk for ischemic stroke increases when total cholesterol is above 280 mg/dL. Other studies suggest that high cholesterol poses a risk for stroke only when specific proteins associated with inflammation are present. [For more information, see In-Depth Report #45: Stroke.]

Resources

www.nhlbi.nih.gov/about/ncep -- National Cholesterol Education Program
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.acc.org -- American College of Cardiology
www.americanheart.org -- American Heart Association
www.eatright.org -- American Dietetic Association

References

AHA; ACC; National Heart, Lung, and Blood Institute, Smith SC Jr, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update endorsed by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol. 2006 May 16;47(10):2130-9.

Armitage J. The safety of statins in clinical practice. Lancet. 2007 Nov 24;370(9601):1781-90.

Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007 Sep 27;357(13):1301-10.

Briel M, Ferreira-Gonzalez I, You JJ, Karanicolas PJ, Akl EA, Wu P, et al. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis. BMJ. 2009 Feb 16;338:b92. doi: 10.1136/bmj.b92.

Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O'Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: The METEOR Trial. JAMA. 2007 Mar 25; [Epub ahead of print]

Daniels SR, Greer FR; Committee on Nutrition. Lipid screening and cardiovascular health in childhood. Pediatrics. 2008 Jul;122(1):198-208.

Ford I, Murray H, Packard CJ, Shepherd J, Macfarlane PW, Cobbe S. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med. 2007 Oct 11;357(15):1477-86.

Gaziano M, Manson JE, Ridker PM. Primary and secondary prevention of coronary heart disease. In: Libby P, Bonow RO, Mann DL, Braunwald E, Zipes DP, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed. Saunders; 2007;chap 45.

Hlatky MA. Expanding the orbit of primary prevention--moving beyond JUPITER. N Engl J Med. 2008 Nov 20;359(21):2280-2. Epub 2008 Nov 9.

Jolliffe CJ, Janssen I. Distribution of lipoproteins by age and gender in adolescents. Circulation. 2006 Sep 5;114(10):1056-62. Epub 2006 Aug 28.

Kodama S, Tanaka S, Saito K, Shu M, Sone Y, Onitake F, et al. Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis. Arch Intern Med. 2007 May 28;167(10):999-1008.

McCrindle BW, Urbina EM, Dennison BA, Jacobson MS, Steinberger J, Rocchini AP, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents. A scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, With the Council on Cardiovascular Nursing. Circulation. 2007 Mar 21; [Epub ahead of print]

Park MK. Dyslipidemia and Other Cardiovascular Risk Factors. In: Pediatric Cardiology for Practitioners, 5th ed. Mosby; 2008:chap 33.

Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195-207. Epub 2008 Nov 9.

Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Nov 27;166(21):2307-13.

US Preventive Services Task Force. Screening for lipid disorders in children: US Preventive Services Task Force recommendation statement. Pediatrics. 2007 Jul;120(1):e215-9.

Reviewed last on: 5/5/2009
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

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