Lipid Disorders in the Elderly☆

Wilbert S Aronow, New York Medical College, Valhalla, NY, United States
r 2014 Elsevier Inc. All rights reserved.

Glossary Dyslipidemia a lipid disorder consisting of hypercholes-

Atherosclerotic cardiovascular disease A disorder affect-
ing medium and large arteries in which subintimal deposits
of lipids and connective tissue cause a decrease or an
obstruction of blood flow through the arteries; includes
coronary artery disease, peripheral arterial disease, carotid
arterial disease, cerebrovascular disease, and abdominal
aortic aneurysm
Coronary artery disease a disorder in which one or more
coronary arteries are narrowed by atherosclerotic plaques or
vascular spasm; includes stable and unstable angina pec-
toris, myocardial infarction, and sudden cardiac death
terolemia, increased serum low-density lipoprotein (LDL)
cholesterol, decreased serum high-density lipoprotein
(HDL) cholesterol, hypertriglyceridemia, or combinations
there of. The incidence of atherosclerotic cardiovascular
disease (ASCVD) is much higher in older men and women
than in younger men and women, suggesting that an
elevated serum low-density lipoprotein (LDL) cholesterol
may contribute more to the burden of atherosclerotic
vascular disease in the elderly than in the young.

Introduction

Cholesterol, cholesteryl esters, and triglycerides are fats or lipids. To circulate in blood, these lipids are combined with phos-
pholipids and protein in particles called lipoproteins. Only three classes of lipoproteins–LDL, high-density liporotein (HDL), and
very low-density lipoprotein (VLDL) –are found in the serum of fasting persons.
Following ingestion of a fat-containing meal, cholesterol and triglyceride are absorbed from the intestine and transported in
chylomicrons via intestinal lacteals and the thoracic duct to the plasma compartment to produce the alimentary lipemia that can
give rise to lactesence in postprandial plasma. Cholesterol and triglyceride of endogenous origin also enter the plasma com-
partment from the liver as VLDL. Both chylomicrons and VLDL are converted to somewhat smaller, denser, relatively cholesterol-
enriched remnant lipoproteins following the selective extraction of triglyceride by the enzyme lipoprotein lipase. The remnant
lipoproteins are removed from the plasma by hepatic chylomicron receptors that recognize surface apolipoprotein E and/or the
structural apolipoprotein B100 or are further metabolized by hepatic triglyceride lipase to LDL and then removed by LDL
receptors. HDL is composed principallyof apolipoproteins A-I and A-II and cholesterol and phospholipid. HDL is synthesized in
both the intestine and the liver, and it acquires cholesterol by exchange from triglyceride-rich lipoproteins and in the process of
facilitating reverse transport of cholesterol from the periphery to the liver, where it is excreted in the bile unchanged or after
conversion to bile acids.
LDL is the major cholesterol-containing lipoprotein implicated in the development of atherosclerosis and is the primary target of
therapeutic hypolipidemic interventions. LDL cholesterol may be elevated to undesirable levels because of excessive intake of dietary
cholesterol and saturated fat (especially the latter), obesity (and increased hepatic synthesis), and/or genetic disorders that increase
synthesis or impair LDL removal (e.g., LDL receptor deficiency in familiar hypercholesterolemia) or because of secondary causes such as
hypothyroidism, nephrotic syndrome, renal failure, and biliary cirrhosis. LDL levels may be decreased in certain genetic disorders
associated with hypocholesterolemia (e.g., familial hypobetalipoproteinemia, a so-called longevity syndrome) but are also seen in
inflammatory syndromes commonly seen in frail persons, especially prevalent in elderly persons in hospitals or long-term care settings.
HDL is synthesized in both the liver and the intestine, and it exerts a protective effect on the development of atherosclerotic
vascular disease. In addition to reducing arterial tissue cholesterol levels that contribute to such atherosclerosis by facilitating
reverse cholesterol transport, HDL inhibits oxidation and aggregation of LDL in the arterial wall. Lower HDL cholesterol may be
associated with genetic disorders, nutritional habits (high carbohydrate intake), obesity, hypertriglyceridemia, cigarette smoking,
and lack of exercise, whereas HDL levels are increased with alcohol ingestion and estrogens or in familial hyper-
alphalipoproteinemia, another longevity syndrome.

☆
Change History: WS Aronow August 2014. Abstract and keywords added. Further reading includes 9 references, 8 of which are new. The 2013 American
College of Cardiology (ACC)/American Heart Association (AHA) lipid guidelines state that ASCVD includes CAD, stroke, transient ischemic attack, and PAD
which includes carotid arterial disease and abdominal aortic aneurysm as well as PAD of the lower extremities. These guidelines use a Pooled Heart Equation
to estimate the 10-year risk of developing ASCVD. This equation includes sex, age, race, total cholesterol, HDL cholesterol, systolic blood pressure, treatment
for hypertension, diabetes mellitus, and smoking. High-dose statins and moderate-dose statins are discussed. New clinical trial data on use of statins for
secondary prevention and for primary prevention are discussed. The 2013 American College of Cardiology/American Heart Association lipid guidelines are
discussed extensively.
This article is an update of Wilbert S. Aronow, Lipid Disorders in the Elderly, In Encyclopedia of Endocrine Diseases, edited by Luciano Martini, Elsevier, New
York, 2004, Pages 178-181.

Encyclopedia of Endocrine Diseases, Second Edition, Volume 1 doi:10.1016/B978-0-12-801238-3.03870-8 719

720 Lipid Disorders in the Elderly

VLDL is a triglyceride-rich lipoprotein synthesized and secreted by the liver. Hypertriglyceridemia is associated with genetic
disorders, obesity, diabetes mellitus, renal failure, heavy alcohol intake, and drugs such as estrogens.
The measurement of fasting levels of LDL cholesterol, HDL cholesterol, and triglycerides in the serum is obtained as part of
comprehensive assessment of the risk of ASCVD that is commonly estimated according to the following formula: total choles-
terol ¼LDL cholesterol þ HDL cholesterol þ triglycerides/5. Dyslipidemia includes hypercholesterolemia, an increased LDL cho-
lesterol, a decreased HDL cholesterol, and hypertriglyceridemia. Hypercholesterolemia is diagnosed if the serum total cholesterol is
200 mg dl1 (5.2 mmol l1) or higher. A low serum HDL cholesterol is less than 40 mg dl1 (1.04 mmol l1) in men and less
than 50 mg dl1 (1.2 mmol l1) in women. Hypertriglyceridemia is a triglycerides level of 150 mg dl1 (3.9 mmol l1) or higher.
Patients with atherosclerotic vascular disease should have their LDL cholesterol reduced to less than 70 mg dl1 (1.82 mmol l1).
Increased LDL cholesterol and decreased HDL cholesterol are risk factors for coronary artery disease (CAD), peripheral arterial
disease (PAD), ischemic stroke, transient ischemic attack, carotid arterial disease, heart failure, abdominal aortic aneurysm,
valvular aortic stenosis, and mitral annular calcium in elderly persons.
The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) lipid guidelines state that ASCVD
includes CAD, stroke, transient ischemic attack, and PAD which includes carotid arterial disease and abdominal aortic aneurysm as
well as PAD of the lower extremities. These guidelines use a Pooled Heart Equation to estimate the 10-year risk of developing
ASCVD. This equation includes sex, age, race, total cholesterol, HDL cholesterol, systolic blood pressure, treatment for hyper-
tension, diabetes mellitus, and smoking.

Lifestyle Measures

Persons with hypercholesterolemia with and without ASCVD should be treated with a Step II AHA diet. They should achieve and
maintain an ideal body weight. Cholesterol intake should be less than 200 mg/day. Less than 30% of total caloric intake should be
fatty acids. Saturated fatty acids should comprise less than 7% of total calories, polyunsaturated fatty acids should account for up
to 10% of total calories, and monounsaturated fatty acids should comprise 10–15% of total calories. Protein intake should
account for 10%–20% of total calories. Carbohydrates should comprise 50%–60% of total calories. In addition to loss of weight in
obese persons, daily aerobic exercise, and dietary treatment of hypercholesterolemia, cigarette smoking should be stopped,
hypertension should be treated, and diabetes mellitus controlled with the hemoglobin A1c level reduced to less than 7.0%.
The 2011 ACC/AHA guidelines on treatment of hypertension in the elderly recommend reducing the blood pressure to less
than 140/90 mm Hg in elderly persons younger than age 80 years. In persons aged 80 years and older, these guidelines recom-
mend reducing the systolic blood pressure to 140–145 mmHg if tolerated. The 2013 ACC/AHA guidelines on treatment of
hypercholesterolemia state that lifestyle modification must be used both prior to cholesterol-lowering drug therapy and together
with use of cholesterol-lowering drug therapy.

Metabolic Syndrome

The clustering of high serum triglycerides, small dense LDL particles, low serum HDL cholesterol levels, hypertension, insulin
resistance (with or without glucose intolerance), and a prothrombotic state is diagnosed as the metabolic syndrome. This con-
stellation is extremely common in persons with type 2 diabetes mellitus and is thought to be a precursor to diabetes mellitus in
persons at increased risk for developing diabetes mellitus with aging. The metabolic syndrome should be treated with lifestyle
modification and with statin therapy to treat the atherogenic dyslipidemia of the metabolic syndrome.

Statins

The most effective lipid-lowering drugs in reducing cardiovascular events and mortality in elderly and younger persons are the 3-
hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statin drugs. Statins reduce serum total cholesterol,
LDL cholesterol, and triglycerides, and they increase serum HDL cholesterol. They also cause many pleiotropic effects which
contribute to a reduction in cardiovascular events and mortality. The statin drugs include rosuvastatin, atorvastatin, simvastatin,
pravastatin, lovastatin, fluvastatin, and pitavastatin. Statin drugs suppress cholesterrol biosynthesis by competitively inhibiting
HMG-CoA reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, a precursor of sterols (including
cholesterol). This action induces upregulation of LDL receptors in the liver and increased clearance of LDL receptors in the liver
and increased clearance of LDL from the plasma, thereby reducing plasma cholesterol levels.
High-dose statins (rosuvastatin 20–40 mg daily and atorvastatin (40–80 mg daily) reduce LDL cholesterol 50% or more.
Moderate-dose statins (rosuvastatin 5–10 mg daily, atorvastatin 10–20 mg daily, simvastatin 20–40 mg daily, pravastatin
40–80 mg daily, lovastatin 40 mg daily, fluvastatin XL 80 mg daily, fluvastatin 40 mg twice daily, and pitavastatin 2–4 mg daily)
reduce LDL cholesterol 30%–49%. Low-dose statins reduce LDL cholesterol less than 30%.
Numerous double-blind, randomized, placebo-controlled trials have shown that elderly persons with and without ASCVD or
diabetes mellitus treated with statins have a reduction in cardiovascular events and in mortality. The lower the serum LDL
 Lipid Disorders in the Elderly 721

cholesterol reduced by statins, the greater the reduction in cardiovascular events and mortality. In the Heart Protection Study,
where 5,806 of the 20,536 men and women at increased risk for cardiovascular events randomized to simvastatin or to double-
blind placebo were 70–80 years of age at study entry and were 75–85 years of age at follow-up, 5 years of simvastatin therapy
prevented myocardial infarction, stroke, and revascularization in 70–100 persons per 1,000 treated persons regardless of age,
gender, or initial levels of serum lipids. In this study, reduction of serum LDL cholesterol in persons with a baseline serum LDL
cholesterol of less than 100 mg dl1 (2.6 mmol l1) was as effective in reducing cardiovascular events and mortality as reducing
serum LDL cholesterol in persons with higher serum LDL cholesterol levels.
At 5-year follow-up, compared to placebo, simvastatin significantly decreased all-cause mortality by 13%, any cardiovascular
death by 17%, major coronary events by 27%, any stroke by 25%, coronary or noncoronary revascularization by 24%, and any
major cardiovascular event by 24%.
In the Study Assessing Goals in the Elderly (SAGE), 893 ambulatory CAD patients aged 65–85 years with at least 1 episode of
myocardial ischemia lasting at least 3 min during 48-hour ambulatory electrocardiographic screening were randomized to ator-
vastatin 80 mg daily or to pravastatin 40 mg daily and followed for 12 months. Total duration of myocardial ischemia detected by
48-hour ambulatory electrocardiograms at month 3 and at month 12 after randomization was significantly reduced by both
atorvastatin and pravastatin with no significant difference between the 2 treatment groups. Compared with pravastatin, ator-
vastatin significantly reduced serum LDL cholesterol levels, insignificantly reduced major acute cardiovascular events by 22%, and
significantly reduced all-cause mortality by 67%.
In the Justification for the Use of Statins in Prevention: an Intervention Trial evaluating Rosuvastatin (JUPITER), 17,082
apparently healthy persons, median age 66 years, with a serum LDL cholesterol of less than 130 mg dl1 (3.36 mmol l1) and
high-sensitivity C-reactive protein levels of 2.0 mg l1 or higher were randomized to rosuvastatin 20 mg daily or placebo [42]. At
1.9-year median follow-up, rosuvastatin significantly reduced serum LDL cholesterol levels by 50%, high-sensitivity C-reactive
protein levels by 37%, and the primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for
unstable angina pectoris, or death from cardiovascular causes by 44%.
A meta-analysis was performed in 9 randomized trials of statins for secondary prevention in 19, 569 patients aged 65–82 years
Over 5 years, statins reduced all-cause mortality 22% (95% CI, 11–35%), CAD mortality 30% (95% CI, 17%–47%), nonfatal
myocardial infarction 26% (95% CI, 11%–40%), need for revascularization 30% (95% CI, 17%–47%), and stroke 25% (95% CI,
6%–44%). The estimated number needed to treat to save 1 life was 28.

2013 ACC/AHA Lipid Guidelines

The 2013 ACC/AHA lipid guidelines recommend the use of high-dose statins to adults aged 75 years and younger with ASCVD
unless contraindicated with a class I indication. Moderate-dose or high-dose statins are reasonable to administer to persons with
ASCVD older than 75 years with a class IIa indication. Persons aged 21 years and older with a serum LDL cholesterol of
190 mg dl1 (4.94 mmol l1) or higher should be treated with high-dose statins with a class I indication. For primary prevention
in diabetics aged 40–75 years and a serum LDL cholesterol between 70 and 189 mg dl1 (1.82–4.91 mmol l1), moderate-dose
statins should be administered with a class I indication. For primary prevention in diabetics aged 40–75 years, a serum LDL
cholesterol between 70 and 189 mg dl1 (1.82–4.91 mmol l1), and a 10-year risk of ASCVD of 7.5% or higher calculated from
the Pooled Heart Equation, high-dose statins should be administered with a class IIa indication. For primary prevention in
diabetics aged 21–39 years or older than 75 years and a serum LDL cholesterol between 70 and 189 mg dl1 (1.82-
–4.91 mmol l1), moderate-dose statins or high-dose statins should be administered with a class IIa indication. Adults aged 40–75
years of age without diabetes mellitus or ASCVD with a serum LDL cholesterol between 70 and 189 mg dl1 (1.82-
–4.91 mmol l1) and a 10-year risk of ASCVD of 7.5% or higher calculated from the Pooled Heart Equation should be treated with
high-dose statins or moderate-dose statins with a class I indication. Adults aged 40–75 years of age without diabetes mellitus or
ASCVD with a serum LDL cholesterol between 70 and 189 mg dl1 (1.82–4.91 mmol l1) and a 10-year risk of ASCVD of
5%–7.4% calculated from the Pooled Heart Equation should be treated with moderate-dose statins with a class IIa indication.
Besides the use of statins in these groups, other factors may be considered for use of statins. These factors include a primary
serum LDL cholesterol of 160 mg dl1 (4.16 mmol l1) or higher or other evidence of genetic hyperlipidemia, a family history of
premature ASCVD with onset before age 55 years in a first-degree male relative, onset before age 55 years in a first-degree male
relative or onset before age 65 years in a first-degree female relative, high-sensitivity C-reactive protein 2 mg l1 and higher, a
coronary calcium score of 300 Agaston units or higher or 75% and higher for age, sex, and ethnicity, an ankle-brachial index below
0.90, or an increased lifetime risk of ASCVD.
These guidelines also state that there is no additional ASCVD reduction from adding nonstatin therapy to further lower non-
HDL cholesterol once an LDL cholesterol goal has been reached. Clinical trials have demonstrated no reduction in cardiovascular
events or mortality in persons treated with statins by addition of nicotinic acid, fibric acid derivatives, ezetemibe, or drugs that raise
HDL cholesterol.
Serum triglycerides 500 mg dl1 (13.0 mmol l1) or higher should be treated to reduce the risk of pancreatitis. Gemfibrozil
should not be given to patients on statins. Fenofibrate may be considered with low-dose or moderate dose statins with a class IIb
indication, should not be used if the estimated glomerular filtration rate is less than 30 ml min/1.73 m2, and should not exceed a
dose of 54 mg daily if the estimated glomerular filtration rate is 30–59 ml min/1.73 m2. If omega-3 fatty acids are used to treat
722 Lipid Disorders in the Elderly

serum triglycerides 500 mg dl1 (13.0 mmol l1) or higher, it is reasonable to evaluate the patient for gastrointestinal dis-
turbances, skin changes, and bleeding.
In 18 randomized clinical trials (19 cohorts) for primary prevention of ASCVD by statins which included 56, 934 patients
between 28 and 97 years of age, compared with placebo, statins significantly reduced LDL cholesterol 39 mg dl1 (1.01 mmol l1),
all-cause mortality 14%,fatal and nonfatal cardiovascular disease 25%, fatal and nonfatal CAD 27%, fatal and nonfatal stroke 22%,
and coronary revascularization 38%. The incidence of cancers, myalgia, rhabdomyolysis, liver enzyme elevation, renal dysfunction, or
arthritis did not differ between statins and placebo. The rates of adverse events (17%) and of stopping treatment (12%) did not differ
between statins and placebo. One of 2 trials reported an increased risk of diabetes mellitus caused by statins (number needed to
treat¼198 persons).

See also: Hypercholesterolemia. Hypertriglyceridemias and Their Treatment. Low HDL and High HDL Syndromes

Further Reading
Afilalo, J., Duque, G., Steele, R., et al., 2008. Statins for secondary prevention in elderly patients: A hierarchical Bayesian meta-analysis. Journal of the American College of
Cardiology 51, 37–45.
Aronow, W.S., 2014. Ask the expert. Applying the new statin guidelines to the long-term care population. Annals of Long-Term Care 22 (1), 2–4.
Aronow, W.S., Frishman, W.H., 2010. Management of hypercholesterolemia in older persons for the prevention of cardiovascular disease. Cardiology in Review 18, 132–140.
Aronow, W.S., Fleg, J.l., Pepine, C.J., et al., 2011. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology
Foundation Task Force on Clinical Expert Consensus Documents. Circulation 123, 2434–2506.
Deedwania, P., Stone, P.H., Merz, C.N.B., et al., 2007. Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart
disease. Results of the Study Assessing Goals in the Elderly (SAGE). Circulation 115, 700–707.
Heart Protection Study Collaborative Group, , 2002. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised
placebo-controlled trial. Lancet 360, 7–22.
Ridker, P.M., Danielson, E., Francisco, M.I.A, et al., 2008. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. The New England
Journal of Medicine 359, 2195–2207.
Stone, N.J., Robinson, J., Lichtenstein, A.H., et al., 2014. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults:
a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology 63,
2889–2934.
Taylor, F.C., Huffman, M., Ebrahim, S., 2013. Statin therapy for primary prevention of cardiovascular disease. JAMA 310, 2451–2452.