Metabolism

Total Cholesterol

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Description
The term "cholesterol" usually means total cholesterol (VLDL + LDL + HDL). In recent years. total cholesterol is used less frequently that its components and triglycerides to determine risk for heart disease (Corti et al., 1997).

Cholesterol serves several functions including aiding in the synthesis of bile acids, and in the synthesis of steroid hormones.

Comorbidity may be an important factor to consider when studying cholesterol because older frail persons with a high burden of disease and low cholesterol levels are more likely to have decreased survival than are those with little or no disease and chronically low cholesterol levels (Glynn et al, 1995; Pekkanen et al., 1994; Ettinger et al., 1995).

Significance of Measurement
In middle-aged populations total cholesterol level has been shown to have a direct relation with coronary heart disease and all-cause mortality (Manolio et al., 1992). However, in older persons, it has been shown to have a U- or J-shaped relation (Anderson et al. 1987, Staessen et al., 1990) or to be inversely related or not related to risk for death (Kronmal et al., 1993; Krumholz et al., 1994).

LDL is sometimes referred to as "bad" cholesterol, because elevated levels of LDL correlate most directly with coronary heart disease, while high levels of HDL are protective.

Method of Measurement
A cholesterol test, also called lipid test and lipoprotein test, measures the amount of cholesterol and triglycerides in the blood serum.

To get accurate results for the entire lipid panel, fasting 9 to 12 hours is recommended. Total cholesterol, however, can be measured without fasting. Certain drugs and beverages such as coffee, tea, or soda may affect results.

References
· Anderson, K.M., Castelli, W.P., & Levy, D. (1987). Cholesterol and mortality. 30 years of follow-up from the Framingham study. Journal of the American Medical Association, 257, 2176-2180.
· Corti, M.C., Guralnik, J.M., Salive, M.E., Harris, T., Ferrucci, L., Glynn, R.J., et al. (1997). Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons. Annals of Internal Medicine, 126(10), 753-760.
· Ettinger, W.H. Jr., Harris, T., Verdery, R.B., Tracy, R., & Kouba, E. (1995). Evidence of inflammation as a cause of hypocholesterolemia in older people. Journal of the American Geriatrics Society, 43, 264-266.
· Glynn, R.J., Field, T.S., Rosner, B., Hebert, P.R., Taylor, J.O., & Hennekens, C.H. (1995). Evidence for a positive linear relation between blood pressure and mortality in elderly people. Lancet, 345, 825-829.
· Kronmal, R.A., Cain, K.C., Ye, Z., & Omenn, G.S. (1993). Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data. Archives of Internal Medicine, 153, 1065-1073.
· Krumholz, H.M., Seeman, T.E., Merrill, S.S., Mendes de Leon. C.F., Vaccarino, V., Silverman, D.I., et al. (1994). Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. Journal of the American Medical Association, 272, 1335-1340.
· Manolio, T.A., Pearson, T.A., Wenger, N.K., Barrett-Connor, E., Payne, G.H., & Harlan, W.R. (1992). Cholesterol and heart disease in older persons and women. Review of an NHLBI workshop. Annals of Epidemiology, 2(1-2), 161-176.
· Pekkanen, J., Nissinen, A., Vartiainen, E., Salonen, J.T., Punsar, S., & Karvonen, M.J. (1994). Changes in serum cholesterol level and mortality: A 30-year follow-up. American Journal of Epidemiology, 139, 155-165.
· Staessen, J., Amery, A., Birkenhager, W., Bulpitt, C., Clement, D., de Leeuw, P., et al. (1990). Is a high serum cholesterol level associated with longer survival in elderly hypertensives? Journal of Hypertension, 8, 755-761.

HDL Cholesterol

Glycosylated Hemoglobin

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Description
Measured by the HbA1c test, Glycosolated Hemoglobin is a measure of the amount of sugar that is attached to the hemoglobin in red blood cells (http://www.nlm.nih.gov/medlineplus/ency/article/003640.htm). The results are reported as a percentage. People without diabetes usually have a result of about six percent in this test. Because red blood cells live in the bloodstream for approximately four months, the HbA1c test shows the average blood sugar for the past 2 to 3 months and is an indicator of glucose metabolism over that time.
Unlike other blood sugar tests, the HbA1c test is not affected by short-term changes. Glycosylated hemoglobin can be a good measure of how well diabetes is managed over time (http://www.nlm.nih.gov/medlineplus/ency/article/003640.htm).

Significance of Measurement
Higher test values are associated with higher risk of complications from diabetes (eye disease, kidney disease, nerve damage, heart disease, and stroke) (http://www.nlm.nih.gov/medlineplus/ency/article/003640.htm). Only a small percentage of the hemoglobin molecules in red blood cells become glycosylated (that is, chemically linked to glucose). The percent of glycosylation increases over time and increases with more glucose in the blood. Therefore, older red blood cells will have a greater percent of glycosylated hemoglobin, and diabetics whose blood glucose has been too high will have a greater percent of glycosylated hemoglobin (http://www.nlm.nih.gov/medlineplus/ency/article/003640.htm).
Levels of glycosylated hemoglobin indicating poor glycemic control among diabetics have been related to poor cognitive function in some studies (Reaven et al., 1990; Gradman et al., 1993; Perlmuter, 1984; Jagusch et al., 1992). However, no such association was observed in other studies (Worrall et al., 1993; Lowe et al. 1994).

Method of Measurement
Glycosylated hemoglobin can be assayed from blood samples or blood spots.

References
· Gradman, T.J., Laws, A., Thompson, L.W., & Reaven, G.M. (1993). Verbal learning and/or memory improves with glycemic control in older subjects with non-insulin dependent diabetes mellitus. Journal of the American Geriatrics Society, 41, 1305–1312.
· Jagusch, W., Cramon, D.Y.V., Renner, R., & Hepp, K.D. (1992). Cognitive function and metabolic state in elderly diabetic patients. Diabetes Nutrition and Metabolism, 5, 265–274.
· Lowe, L.P., Tranel, D.T., Wallace, R.B., & Welty, T.K. (1994). Type II diabetes and cognitive function. Diabetes Care, 17, 891-896.
· Perlmuter, L.C., Hakami, M.K., Hodgson-Harrington, C., Ginsberg, J., Katz, J., Singer, D.E., et al. (1984). Decreased cognitive function in aging non-insulin-dependent diabetic patients. American Journal of Medicine, 77, 1043–1048.
· Reaven, G.M., Thompson, L.W., Nahum, D., & Haskins, E. (1990). Relationship between hyperglycemia and cognitive function in older NIDDM patients. Diabetes Care, 13, 16–21.
· U.S. National Library of Medicine & National Institutes of Health. (2003). medline plus: Trusted health information for you. Retrieved March 28, 2005, from http://www.nlm.nih.gov/medlineplus/ency/article/003640.htm
· Worrall, G., Moulton, N., & Briffett, E. (1993). Effect of type II diabetes mellitus on cognitive function. Journal of Family Practice, 36, 639–643.

LDL Cholesterol

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Description
Low-Density Lipoprotein (LDL) cholesterol is a type of lipoprotein that carries most of the cholesterol in the blood. A high level of LDL is associated with atherosclerosis and an increasing risk of heart disease. That’s why LDL is called “bad” cholesterol.

LDL-cholesterol is measured to assess risk for CHD and to follow the progress of patients being treated to lower LDL-cholesterol concentrations. In general, a desirable level of LDL-cholesterol is below 130 mg/dL; borderline high is from 130/159 mg/dL; high is 160/189 mg/dLl and very high LDL-cholesterol is greater than or equal to 190 mg/dL. Recently, recommended target levels of cholesterol have been lowered for those with diabetes and other heart disease risk factors. Those who have established coronary disease and diabetes (or metabolic syndrome or smoking or acute coronary syndrome) have a recommended target for an LDL-cholesterol level less than 70 mg/dL (Grundy et al., 2004).

Significance of Measurement
A high level of LDL cholesterol contributes to the development of coronary atherosclerosis, and increases the risk of heart disease including heart attack (Reed et al., 1986). Among older persons, studies have showed inconsistent findings on the relationship between LDL and health outcomes such as heart disease and mortality (Benfante et al., 1992; Corti et al., 1995; Frost et al., 1996; Jacobs et al., 1992; Krumholz et al., 1994; Karlamangla et al., 2004; Kronmal et al., 1993; Raiha et al., 1997; Fried et al., 1998; Weverling-Rijnsburger et al., 1997),

Method of Measurement
LDL cholesterol level is based on a blood test (serum or plasma). The blood sample is often collected by venipuncture or fingerstick. This blood test is done after a 9-12 hour fast. In NHANES, serum LDL was calculated on examinees who fasted at least nine hours in the morning.

LDL-cholesterol is calculated from measured values of total cholesterol, triglycerides, and HDL-cholesterol according to the Friedewald calculation:

[LDL cholesterol] = [total cholesterol] - [HDL-cholesterol] - [triglycerides/5]

where [triglycerides/5] is an estimate of VLDL cholesterol. The calculation is valid only for triglycerides less than 400 mg/dL
(http://www.cdc.gov/nchs/data/nhanes/frequency/l13amdoc.pdf).

References:
· Benfante, R., Reed, D., & Frank, J. (1992). Do coronary heart disease risk factors measured in the elderly have the same predictive roles as in the middle aged? Comparisons of relative and attributable risks. Annals of Epidemiology, 2, 273-282.
· Corti, M.C., Guralnik, J.M., Salive, M.E., Harris, T., Field, T.S., Wallace, R.B., et al. (1995). HDL cholesterol predicts coronary heart disease mortality in older persons. Journal of the American Medical Association, 274, 539-544.
· Fried, L.P., Kronmal, R.A., Newman, A.B., Bild, D.E., Mittelmark, M.B., Polak, J.F., et al. (1998). Risk factors for 5- year mortality in older adults. Journal of the American Medical Association, 279(8), 585-592.
· Frost, P.H., Davis, B.R., Burlando, A.J., Curb, J.D., Guthrie, G.P., Isaacsohn, J.L., et al. (1996). Serum lipids and incidence of coronary heart disease: Findings from the Systolic Hypertension in the Elderly Program (SHEP). Circulation, 94, 2381-2388.
· Grundy, S.M., Cleeman, J.I., Merz, C.N.B., Brewer, H.B.Jr, Clark, L.T., Hunninghake, D.B., et al. (2004). Implications of recent clinical trials for the national cholesterol education program Adult Treatment Panel III Guidelines. Circulation, 110, 227-239.
· Jacobs, D., Blackburn, H., Higgins, M., Reed, D., Iso, H., McMillan, G., et al. (1992). Report of the conference on low blood cholesterol: Mortality associations. Circulation, 86, 1046-1060.
· Kronmal, R.A., Cain, K.C., Ye, Z., & Omenn, G.S. (1993). Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data. Archives of Internal Medicine, 153, 1065-1073.
· Krumholz, H.M., Seeman, T.E., Merrill, S.S., de Leon, C.F.M., Vaccarino, V., Silverman, D.I., et al. (1994). Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. Journal of the American Medical Association, 272(17), 1335-1340.
· Karlamangla, A.S., Singer, B., Reuben, D.B., & Seeman, T.E. (2004). Increases in serum non-high-density lipoprotein cholesterol may be beneficial in some high-functioning older adults: MacArthur Studies of Successful Aging. Journal of the American Geriatrics Society, 52(4), 487-494.
· National Center for Health Statistics. (2005). NHANES 1999-2000 data release: Laboratory 13AM- triglycerides and HDL-cholesterol. Retrieved March 25, 2005, from http://www.cdc.gov/nchs/data/nhanes/frequency/l13amdoc.pdf
· Raiha, I., Marniemi, J., Puukka, P., Toikka, T., Ehnholm, C., & Sourander, L. (1997). Effect of serum lipids, lipoproteins, and apolipoproteins on vascular and nonvascular mortality in the elderly. Arteriosclerosis, Thrombosis, and Vascular Biology, 17, 1224-1232.
· Reed, D., Yano, K., & Kagan, A. (1986). Lipids and lipoproteins as predictors of coronary heart disease, stroke and cancer in the Honolulu Heart Program. American Journal of Medicine, 80, 871-878.
· Weverling-Rijnsburger, A.W.E., Blauw, G.J., Lagaay, A.M., Knook, D.L., Meinders, A.E., & Westendorp, R.G.J. (1997). Total cholesterol and risk of mortality in the oldest old. Lancet, 350, 1119-1123.

Triglycerides

Description
Triglycerides are a fatty substance in the body that is stored as energy for later use. Triglycerides are often included among the lipid indicators in metabolic syndrome, or as part of an evaluation of coronary risk factors. Triglycerides are measured enzymatically in blood serum or plasma using a series of coupled reactions in which triglycerides are hydrolyzed to produce glycerol. Glycerol is then oxidized using glycerol oxidase, and H2O2, one of the reaction products, is measured (http://www.cdc.gov/nchs/data/nhanes/frequency/l13amdoc.pdf).

The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) adopts the following classification of triglyceride levels: Normal fasting triglyceride levels are below 150 mg/dL: 150-199 mg/dL is considered borderline high, 200-499 mg/dL high, and 500 mg/dL and greater very high (Expert Panel, 2001).

Significance of Measurement
High triglyceride levels have been associated with heart disease such as heart attack (Gaziano et al., 1997), coronary heart disease (CHD) (Cullen, 2000), and coronary artery disease (CAD) (Linton & Fazio, 2003). Very high triglycerides can result in pancreatitis (Toskes, 1990). Elevated triglycerides are one of the factors of the metabolic syndrome, which represents a constellation of lipid and nonlipid risk factors of metabolic origin (Expert Panel, 2001). Triglycerides are also measured because the value is used to calculate LDL-cholesterol concentrations (http://www.cdc.gov/nchs/data/nhanes/frequency/l13amdoc.pdf).

Method of Measurement
A blood sample is drawn from a vein or a fingerstick. Reliable triglyceride levels require fasting status.

References
· Cullen, P. (2000). Evidence that triglycerides are an independent coronary heart disease risk factor. American Journal of Cardiology, 86(90), 943-949.
· Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. (2001). Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Journal of the America Medical Association, 285(19), 2486-2497.
· Gaziano, J. M., Hennekens, C. H., O'Donnell, C. J., Breslow, J. L., & Buring, J. E. (1997). Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation, 96(8), 2520-2525.
· Linton, M.F., & Fazio, S. (2003). A practical approach to risk assessment to prevent to coronary artery disease and its complications. American Journal of Cardiology, 92(1,supple), 19i-26i.
· National Center for Health Statistics. (2005). NHANES 1999-2000 data release: Laboratory 13AM- triglycerides and HDL-cholesterol. Retrieved March 23, 2005, from http://www.cdc.gov/nchs/data/nhanes/frequency/l13amdoc.pdf
· Toskes, P. (1990). Hyperlipidemic pancreatitis. Gastroenterology Clinics of North America, 19(4), 783-791.

Insulin

Glucose