Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2754_Библиотеки_им_академика_М_И_Перельмана
.pdf
156 BASIC SKILLS IN INTERPRETING LABORATORY DATA
https://t.me/med1917
it may cause interference in measurement of other laboratory
tests such as alanine aminotransferase and aspartate aminotransferase, which depend on spectrophotometric methods for
analysis. Most technologists and automated systems can identify
lipemic samples, and processes can be used to remove lipemia.
is produces a clear specimen and eliminates interferences in
these assay methods.
Low-Density Lipoprotein Cholesterol
For adults ≥20 years, LDL levels are categorized in the following ways12:
desirable: <100 mg/dL (2.6 mmol/L)
above desirable: 100 to 129 mg/dL (2.6 to 3.3 mmol/L)
borderline high: 130 to 159 mg/dL (3.4 to 4.1 mmol/L)
high: 160 to 189 mg/dL (4.1 to 4.9 mmol/L)
very high: ≥190 mg/dL (4.9 mmol/L)
Low- density lipoprotein cholesterol can be measured directly
or estimated indirectly by a method determined by Friedewald.30
e Friedewald formula subtracts the HDL and VLDL cholesterol from TC. e VLDL is estimated to be the TG level divided
by ve. Using the following formula (all in milligrams/ deciliter),
LDL may be estimated in patients with a TG concentration
<400mg/dL (4.5 mmol/L):
LDL = TC – HDL – (TGs/5)
If a patient’s serum TG concentration exceeds 400 mg/dL
(4.5 mmol/L), LDL cholesterol should not be calculated with
this formula. A direct LDL measurement by laboratory would
provide an LDL value. In patients with severe hypertriglyceridemia, TG- lowering therapy is oen implemented to reduce pancreatitis risk. Once TG values have decreased to <400 mg/dL
(4.5 mmol/L), a standard lipid panel provides LDL cholesterol
data. Clinicians should be aware that other factors, such as low
LDL levels (<70 mg/dL), especially when TGs are above normal,
may also aect the reliability of the Friedewald equation and
that calculation adjustments have been published.
ACC guidelines recommend initiating statin therapy in patients
based on ASCVD risk.1 Patients at high risk, including presence of clinical ASCVD or very high LDL levels (≥190 mg/dL or
≥4.9mmol/L), would benet from high- intensity statin therapy,
with a goal LDL reduction of ≥50%. In patients between 40 and
75 years of age with diabetes, a moderate intensity statin with
a goal LDL reduction of 30% to 49% is recommended. Ahighintensity statin can be considered for select patients with diabetes with additional risk factors. For all other patients (ie, patients
considered for primary prevention therapy without diabetes),
an estimation of ASCVD risk is recommended via use of a risk
calculator. Ten-
year ASCVD risk calculations of 7.5% to 19.9%
are classied as intermediate risk, whereas ≥20% are high risk.
A patient’s ASCVD risk calculation and the presence of riskenhancing factors (eg, family history of premature ASCVD,
chronic kidney disease, metabolic syndrome) can help guide
the clinician–patient risk discussion on statin therapy. When
risk discussion favors the initiation of statin therapy, a moderate intensity statin can be used in patients with an intermediate ASCVD risk calculation, whereas a high- intensity statin can
1,31,32
AHA/
be recommended in a patient with a high 10- year ASCVD risk
(
Minicases 2 and 3).
Lifestyle modications aimed at lowering ASCVD risk are
appropriate for all patients.1 Detailed education should be provided to patients regarding the adoption of a low saturated fat
diet that reduces the percent of calories from saturated fats and
avoids trans fats.
4,33
Physical activity should also be encouraged,
with a goal of at least 150 min/wk of moderate- intensity exercise. Improvements in diet and physical activity are imperative
to aid in weight loss in overweight or obese patients. A weight
loss of ≥5% has been associated with a signicant improvement
in LDL and TGs.4 For patients at elevated ASCVD risk, lifestyle modications with concurrent statin therapy should be
recommended.
1
High-Density Lipoprotein Cholesterol
For adults ≥20 years, HDL levels are categorized in the following ways
genic factor.12 Whereas a high HDL concentration is associated
with cardioprotection, low levels are associated with increased
risk of ASCVD. e Framingham Study demonstrated that
higher HDL levels are protective against cardiovascular risk,
even in the setting of elevations in LDL.34 HDL has several antiatherogenic properties, such as reverse cholesterol transport and
antiplatelet activity; however, clinical studies aimed at raising
HDL with medications have failed to demonstrate a decrease in
cardiovascular risk.
ciation between low HDL and cardiovascular risk is not fully
understood. It is possible that low HDL may be a marker of other
atherogenic changes in the full lipid prole.
<50 mg/dL (1.3 mmol/L) in women is considered a risk fac
tor of metabolic syndrome.1 Most patients with low HDL levels
have concomitant elevated TG levels.6 In these patients, lifestyle
therapy or drug therapy to decrease other atherosclerotic particles usually results in a desirable increase in HDL.34 HDL is
negatively correlated with TGs, smoking, and obesity and positively correlated with physical activity and smoking cessation.
Women typically have higher HDL levels than men, likely due to
the benecial eects of estrogen.
drug therapy decisions are not centered on raising HDL alone.
12
:
low (men): <40 mg/dL (1.0 mmol/L)
low (women): <50 mg/dL (1.3 mmol/L)
Based on epidemiologic evidence, HDL acts as an antiathero-
12,34
erefore, the mechanism of the asso-
HDL cholesterol <40 mg/dL (1.0 mmol/L) in men or
6,34
Because of a lack of evidence,
Non–High-Density Lipoprotein Cholesterol
For adults ≥20 years, non-HDL levels are categorized in the following ways
desirable: <130 mg/dL (3.4 mmol/L)
above desirable: 130 to 159 mg/dL (3.4 to 4.1 mmol/L)
borderline high: 160 to 189 mg/dL (4.1 to 4.9 mmol/L)
high: 190 to 219 mg/dL (4.9 to 5.7 mmol/L)
very high: ≥220 mg/dL (5.7 mmol/L)
Non-HDL cholesterol (TC−HDL) provides an estimate of
thesum of cholesterol carried by atherogenic particles that
12
:
-
1
CHAPTER 8 • LiPid disoRdERs 157
https://t.me/med1917
MINICASE 2
Primary Prevention
Julia K., a 46- year- old woman, presents to the clinic for a new
patient consultation. She has been receiving care from a specialist
(rheumatologist) but has not seen a primary care provider in many
years. Her past medical history includes rheumatoid arthritis but
no other chronic conditions; she is premenopausal and has an
intrauterine device for pregnancy prevention. Her only medication
is biweekly adalimumab, and she states the medication controls her
symptoms well. She does not follow a specific diet but notes that
she tries to limit her fast- food intake and eat a variety of fruits and
vegetables. She walks at a moderate pace for 30 minutes three times
a week. She denies any current tobacco use; she quit 10years ago
after smoking one pack per day for 10 years. She reports drinking
one to two glasses of wine once a month. Her family history is
notable, with a father who had a myocardial infarction at age 54. At
her office visit, she has an unremarkable physical exam with a blood
pressure reading of 112/74mm Hg. She had a set of labs drawn the
previous day that were nonfasting. The following laboratory results
were obtained: TC, 270 mg/dL; HDL, 48 mg/dL; TG, 135 mg/dL; LDL,
195 mg/dL; and glucose, 102 mg/dL. Electrolyte, hematology, liver,
renal, and thyroid tests are all normal. She is 5'6" and weighs 159 lb.
QUESTION: How should the lipid results be interpreted? Based on
this interpretation, is medication therapy recommended?
DISCUSSION: Julia K. is asymptomatic and follows a reasonable
lifestyle that includes a diet rich in fruits and vegetables, routine
aerobic exercise, no tobacco use, and low alcohol intake.
Autoimmune disorders such as rheumatoid arthritis may be a
secondary cause of dyslipidemia, and chronic inflammatory
conditions may be a risk- enhancing factor for ASCVD.1 She does
not have type 2 diabetes or thyroid, renal, or liver disease. She has a
family history of premature ASCVD, with her father having a clinical
ASCVD event at an age <55 years.
Guidelines recommend checking a lipid panel in a fasting or
nonfasting state because evidence suggests the variation between
fasting and nonfasting results is clinically insignificant if labs are
drawn after a standard meal.1 Julia K.’s LDL is very high, her TC is
high, her HDL is low, and her TGs are in normal range. The primary
concern is the very high LDL because LDL ≥190 mg/dL highly
suggests the presence of a primary lipid disorder. Patients with very
high LDL cholesterol are known to be at an increased lifetime risk
for ASCVD events because of their lifetime exposure to elevated
atherogenic cholesterol. Julia K. would be considered high risk for
ASCVD because of her very high LDL.
Julia K. should be encouraged to adhere to a low saturated fat diet
that emphasizes reduced saturated fat and avoidance of trans fat
and to maintain her physical activity. Because she is considered at
high risk, highguidelines recommend high- intensity statins for all adult patients
with an LDL ≥190 mg/dL.1 Once treatment is started, a repeat lipid
panel could be ordered in 4 to 12 weeks to assess for adherence
and percentage reduction in LDL.
intensity statin therapy is recommended. AHA/ACC
contain apolipoprotein B (apoB) such as LDL, VLDL chylomicrons, and Lp(a).
1,12
For patients at very-high ASCVD risk
(eg, multiple ASCVD events), non-HDL levels as well as LDL
levels may guide when nonstatin therapies (eg, ezetimibe) are
recommended.
1
Risk-Enhancing Factors
A number of risk- enhancing factors may be incorporated into
patient- specic ASCVD risk assessment, including apoB, Lp(a),
and high- sensitivity C reactive protein (hs-CRP).1 ApoB and
Lp(a) are lipid specic markers whereas hs-CRP is an inammatory marker. Current AHA/ACC guidelines do not oer
specic testing recommendations for these laboratory tests.
However, guidelines do recommend considering these results,
when available, as part of the clinician–patient risk discussion,
especially for primary prevention in patients at either borderline or intermediate risk. Elevated levels of these markers imply
higher ASCVD risk and support statin initiation for primary
prevention or the intensication of statin therapy in patients
with high- risk or very high- risk ASCVD. ApoB is a major component of all atherogenic lipoproteins; however, apoB levels have
not demonstrated superiority over non-HDL levels in ASCVD
risk prediction.12 us, apoB is typically not measured because
non-HDL is readily available with a standard lipid prole. Lp(a)
is an atherogenic lipoprotein that can predict elevated ASCVD
35
risk independent of other atherogenic lipid values.
Lp(a) levels are stable throughout a patient’s life and are not aected by
diet, exercise, fasting status, or statins. ere is concern about
the lack of standardization of Lp(a) measurement in clinical
laboratories, and results may be reported in either milligrams/
deciliter or nanomoles/liter. ere is no acceptable conversion
factor between the two units, and the preference is for assays
that are calibrated and report results in nanomoles/liter. Currently, no evidence exists that treatment directed at lowering
Lp(a) provides any additional ASCVD risk reduction beyond
guideline recommendations. Of the LDL- lowering drugs, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors
have been shown to lower Lp(a). Finally, hs-CRP is an inammatory marker that has been linked to excess ASCVD risk.
1,36
In a meta- analysis, elevated hs-CRP levels were linked to the
risk of cardiovascular events, cerebrovascular events, and cardiovascular mortality.37 erefore, current AHA/ACC guidelines
consider elevated hs-CRP levels as a risk enhancing factor to be
incorporated into a patient’s ASCVD risk assessment.1 Currently,
there are no clear recommendations on when these laboratory
markers should be ordered, but elevated results can assist in
identifying patients who benet from statin initiation or intensication of LDL- lowering therapy.
When the ASCVD risk assessment, including a lipid panel,
results in an uncertain statin therapy decision, the coronary
158 BASIC SKILLS IN INTERPRETING LABORATORY DATA
https://t.me/med1917
MINICASE 3
Secondary Prevention
James P., a 62- year- old man who is 5' 9" and weighs 260 lb, presents
to the clinic after a positive stress test and is diagnosed with stable
angina. He reported chest pain and shortness of breath with physical
exertion that prompted the stress test. His past medical history is
significant for obesity, hypertension treated with hydrochlorothiazide,
and tobacco dependence. He does not have a history of diabetes or
thyroid disorder. In addition to his hydrochlorothiazide, he is being
prescribed metoprolol succinate, atorvastatin, and low- dose aspirin
daily. He is hesitant to start these new medications and wonders if
they are all necessary. He has never previously taken cholesterollowering medication. He does plan to quit smoking, has already
purchased a nicotine replacement patch, and has set a quit date
in the next week. His wife does most of the cooking and tries to
prepare low- fat and low- salt meals, but he eats fast food for lunch
most days of the week. He does not exercise routinely because
exercise was limited by his chest pain but he would like to start
walking regularly. His mother died of a stroke at age 62.
His blood pressure today at the clinic is 138/86mm Hg, and his
heart rate is 80 beats/min. Fasting lipid profile is as follows: TC,
212 mg/dL; TG, 160 mg/dL; LDL, 140 mg/dL; and HDL 40 mg/dL.
Fasting glucose is 88 mg/dL; electrolyte, hematology, liver, renal,
and thyroid test results are all normal.
QUESTION: How should the lipid profile be interpreted? Why should
James P. receive a prescription for a lipid- lowering medication?
DISCUSSION: Even before this diagnosis, James P. was at risk for
clinical ASCVD. At that time, he was an obese, male smoker— older
than 45 years— with hypertension who lived a sedentary lifestyle
and had some poor dietary habits. His mother died prematurely
of ASCVD (female age <65 years).1 James P. is obese, which may
contribute to an increase in TGs and decrease in HDL cholesterol;
he has no other evidence of disease- related secondary causes of
dyslipidemia (eg, diabetes, hypothyroidism, obstructive liver disease,
renal dysfunction). However, there are potential substance- or
medication- related secondary causes of dyslipidemia in James P.’s
case. Although hydrochlorothiazide may increase LDL cholesterol
and TGs, the effect is most pronounced at higher doses.11
Consideration of the lowest effective dose for blood pressure control
would be valuable. He is a smoker but does have plans to quit in
the immediate future. Smoking is associated with decreases in HDL
cholesterol. James P.’s newly prescribed beta blocker may impact
the lipid profile by causing decreases in HDL and increases in TGs.
However, James P. should still start therapy with a beta blocker
because the benefits of beta blockers in stable angina outweigh
the impact on the lipid profile.
James P. should initiate therapy with a high- intensity statin
(eg, atorvastatin 40 to 80 mg, rosuvastatin 20 mg). AHA/ACC
recommendations are to initiate a high- intensity statin in all patients
with clinical ASCVD, such as stable angina.1 Lifestyle modifications
are appropriate for James P., including weight loss, increasing
physical activity, and a greater emphasis on reducing saturated fat
and avoiding trans fat in the diet. His smoking cessation efforts
should be supported and assessed periodically. A lipid panel and
hepatic transaminases were performed recently, and no additional
baseline laboratory tests are needed. After starting atorvastatin,
the lipid profile should be repeated in 4 to 12 weeks to check for
adherence and LDL response.
artery calcium (CAC) score is recommended by AHA/ACC
guidelines.
1,38
is is not a laboratory test but a scan that can
assist in guiding decisions of statin initiation in primary prevention. If the CAC score is zero, then patients can be considered lower risk and statin therapy can be delayed. However, in
certain patients (ie, current smokers and patients with diabetes,
premature ASCVD family history, or certain inammatory conditions) ASCVD risk may still be elevated despite the zero CAC
score. Because CAC scans do expose patients to radiation, it is
recommended that these tests be ordered by clinicians who are
knowledgeable in diagnostic radiology.
Point- of-Care Testing Options
In addition to laboratory monitoring, point- of- care testing
(POCT) options that range from at- home testing kits to healthcare practitioner–administered ngerstick tests are available.
Many at- home testing kits only provide TC results, providing
limited results for an ASCVD risk assessment. Other overthe- counter testing kits provide results of the full lipid panel.
At- home tests typically require a patient to apply blood to a card
and mail the sample into a laboratory for processing. In addition to at- home testing methods, there are relatively inexpensive
39,40
compact devices for POCT outside the laboratory that are
waived from the Clinical Laboratory Improvement Amendments. ese devices enable testing for TC, HDL, TGs, and calculated LDL.
One important consideration when evaluating POCT devices
is awareness that some variability may be explained by the fact
that dierent sample types are oen compared. For example, a
ngerstick provides a sample with capillary blood and a venous
draw provides venous whole blood. No strong evidence supports that these two sample types give equivalent results.17 e
general conclusion is capillary blood samples provide lower lipid
values than venous collection. Nevertheless, the POCT devices
are accepted methods for screening for dyslipidemia and are
frequently used at health fairs and other screening opportunities. In any POCT setting, quality control should be ensured to
maintain accuracy of testing.
One of the benets of POCT is that it involves the patient in
the laboratory process. ese visits become opportunities for
the clinician to provide the patient with feedback on progress
and reinforce the steps needed to reduce ASCVD risk. Because
guidelines recommend a complete ASCVD risk assessment on
all adult patients, it is important that patients still follow- up with
CHAPTER 8 • LiPid disoRdERs 159
https://t.me/med1917
TABLE 8-4. Effects of Hypolipemic Medications
DRUG CLASS EFFECTS ON LIPOPROTEINS
HMG-CoA reductase
LDL: ↓ 18%–55%
inhibitors (statins)
TG: ↓ 7%–30%
Ezetimibe
LDL: ↓ 13%–20%
HDL: ↑ 3%–5%
TG: ↓ 5%–11%
Bile acid sequestrants
LDL: ↓ 15%–30%
HDL: ↑ 3%–5%
TG: ↑ 0%–10%
Niacin
LDL: ↓ 5%–25%
HDL: ↑ 15%–35%
TG: ↓ 20%–50%
Fibrates
LDL: ↓ 5%–↑ 20%
HDL: ↑ 10%–20%
TG: ↓ 20%–50%
Omega-3 fatty acids
d
: ↓ 6%–↑ 25%
LDL
HDLd: ↓ 5%–↑ 7%
TG: ↓ 19%–44%
PCSK9 inhibitors
LDL: ↓ 43%–64%
a
SAFETY LABORATORY PARAMETERS
b
Creatine kinase
: ↑
a
Liver transaminasesb: ↑
b
Liver transaminases
: ↑
N/A
c
Serum glucose
: ↑
Uric acidc: ↑
Liver transaminasesc: ↑
Creatine kinaseb: ↑
Serum creatininec: ↑
N/A
N/A
Bempedoic acid
LDL: ↓ 18%
e
: ↓ 6%
HDL
TGe: ↓ 2%–↑ 3%
Uric acidc: ↑
Serum creatininef: ↑
BUNf: ↑
Liver transaminasesf: ↑
Plateletsf: ↑
Creatinine kinasef: ↑
Hemoglobinf: ↓
WBCf: ↓
BUN = blood urea nitrogen; WBC = white blood cell.
a
↑ = increase; ↓ = decrease.
b
Routine monitoring of this lab test is not recommended with use of this drug therapy.
c
Routine monitoring of this lab test is recommended with use of this drug therapy.
d
Different omega-3 fatty acid products exhibit varying effects on LDL and HDL depending on whether product contains both
dehydroepiandrosterone and eicosapentaenoic acid or eicosapentaenoic acid only.
e
This information was not statistically analyzed in clinical trials but rather reported as exploratory endpoints.
f
Due to lack of data, there are no current recommendations for or against routine monitoring of this lab test with use of this drug therapy.
a provider for a complete cardiovascular risk assessment because
lipids are only one component of cardiovascular health.
4
drug therapy. Fibrates and omega-3 fatty acids are considered
drugs for lowering TGs. Niacin is an agent that has a favorable
eect on multiple lipid parameters; however, it is no longer rou-
EFFECTS OF HYPOLIPEMIC
MEDICATIONS
tinely recommended. Specic actions of the drugs and laboratory parameters used for monitoring safety are summarized in
Table8-4.
1,12,28,41-43
Clinicians must be aware of how hypolipemic drugs can inuence laboratory test results. e ultimate goal of drug therapy
SUMMARY
is to reduce ASCVD risk or, in the case of very high TGs alone,
reduce the risk of pancreatitis. In general, HMG-CoA reductase inhibitors (statins), ezetimibe, bile acid sequestrants, PCSK9
inhibitors, and bempedoic acid are considered LDL- lowering
e lipid panel consisting of TC, LDL cholesterol, HDL cholesterol, and TGs is an essential component of ASCVD risk assessment. Assessment of the lipid panel guides the identication
160 BASIC SKILLS IN INTERPRETING LABORATORY DATA
https://t.me/med1917
of patients that may benet from lifestyle modications and/or
drug therapy to reduce ASCVD risk. In the setting of hypertriglyceridemia, assessment of the lipid prole aids the clinician in
identifying patients at risk for pancreatitis and assists with diagnostic, prognostic, and therapeutic decisions. For all patients
with dyslipidemia, periodic measurement of the lipid prole is
recommended to monitor progress and/or adherence.
LEARNING POINTS
1. Who should receive lipid testing?
ANSWER: The lipid panel, including TC, TGs, HDL, and LDL, is
part of the ASCVD risk assessment that is recommended every
4 to 6 years for any adult patient between 20 and 39 years.1 This
monitoring could be repeated more often for adults between 40
and 75 years4 or if a clinician determines that a patient’s ASCVD
risk has increased.
atric patients between 9 and 11 years.
2. Why is the measured LDL marked as calculated or direct?
ANSWER: LDL cholesterol concentrations can be estimated
indirectly by a calculation method determined by Friedewald1:
LDL = TC – HDL – (TGs/5). If a patient’s serum TG concentration
exceeds 400 mg/dL (4.5 mmol/L), LDL cholesterol cannot be
calculated with this formula. Direct measurement of LDL is performed when the calculation would be inaccurate. Laboratory
results typically indicate whether the LDL value is calculated or
directly measured.
3.
If a lipid panel is drawn in the nonfasting state, are the
results clinically usable?
ANSWER: Recent guidelines recommend that a fasting or non-
fasting lipid panel can be used in ASCVD risk assessment.
The lipid panel was historically performed under fasting conditions after a 9- to 12-
change in lipid levels after a meal are less signicant; however,
meals with >50 g of fat may increase TGs substantially.
TG measurement is the focus of the lab or if TGs are >400 mg/dL
in a nonfasting sample, then a fasting lipid panel should be
performed.
REFERENCES
1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/
AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on
the Management of Blood Cholesterol: a report of the American College
of Cardiology/American Heart Association Task Force on Clinical
Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285- e350.PubMed
2. Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke
statistics-2020 update: a report from the American Heart Association.
Circulation. 2020;141(9):e139- e596.PubMed
3. Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular
disease: a scientic statement from the American Heart Association.
Circulation. 2011;123(20):2292-2333.PubMed
4. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline
on the Primary Prevention of Cardiovascular Disease: a report of the
American College of Cardiology/American Heart Association Task Force
on Clinical Practice Guidelines. Circulation. 2019;140:e593- e646.
14
Screening is also recommended in all pedi-
hour fast.
1
16
17
Recent literature suggests the
3,18-20
1,19
If
5. Suchy F. Hepatobiliary function. In: Boron W, El B, eds. Medical
Physiology: A Cellular And Molecular Approach. 2nd ed. Philadelphia, PA:
W.B. Saunders; 2012:980-1007.
6. Rader DJ, Kathiresan S. Disorders of lipoprotien metabolism. In: Jameson
JL, Fauci AS, Kasper DL, et al, eds. Harrison’s Principles of Internal
Medicine. 20th ed. New York, NY: e McGraw-Hill Companies, Inc.;
2018:2889-2902.
7. Freeman MW, Walford GA. Lipoprotein metabolism and the treatment
of lipid disorders. In: Jameson JL, De Groot LJ, de Kretser DM, et al, eds.
Endocrinology: Adult and pediatric. 7th ed. Philadelphia, PA: Saunders
Elsevier; 2016:715-736.
8. Jones PJ, Schoeller DA. Evidence for diurnal periodicity in human
cholesterol synthesis. J Lipid Res. 1990;31(4):667-673.PubMed
9. Civeria F, Pocovi M. Monogenic hypercholesterolemias. In: Garg A, ed.
Dyslipidemias: Pathophysiology, Evaluation and Management. Totowa, NJ:
Humana Press; 2015:177-203.
10. Brahm A, Hegele RA. Primary hypertriglyceridemia. In: Garg A, ed.
Dyslipidemias: Pathophysiology, Evaluation and Management. Totowa, NJ:
Humana Press; 2015:205-220.
11. Simha V. Drug- induced dyslipidemia. In: Garg A, ed. Dyslipidemias:
Pathophysiology, Evaluation and Management. Totowa, NJ: Humana Press;
2015:267-286.
12. Jacobson TA, Ito MK, Maki KC, et al. National lipid association
recommendations for patient- centered management of dyslipidemia:
part1. Full report. J Clin Lipidol. 2015;9(2):129-169.PubMed
13. Panel on Antiretroviral Guidelines for Adults and Adolescents.
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents
with HIV. Department of Health and Human Services. http://www
.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed
Jun 28, 2020.
14. Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association
of Clinical Endocrinologists and American College of Endocrinology
guidelines for management of dyslipidemia and prevention of
cardiovascular disease. Endocr Pract. 2017;23(suppl 2):1-87.PubMed
15. Goldberg IJ, Mosca L, Piano MR, Fisher EA. AHA Science Advisory:
wine and your heart: a science advisory for healthcare professionals from
the Nutrition Committee, Council on Epidemiology and Prevention, and
Council on Cardiovascular Nursing of the American Heart Association.
Circulation. 2001;103(3):472-475.PubMed
16. Expert Panel on Integrated Guidelines for Cardiovascular Health and
Risk Reduction in Children and Adolescents. Expert panel on integrated
guidelines for cardiovascular health and risk reduction in children and
adolescents: summary report. Pediatrics. 2011;128(suppl 5):S213-S256.
PubMed
17. Chen X, Zhou L, Hussain MM. Lipids and dyslipoproteinemia. In:
McPherson RA, Pincus MR, eds. Henry’s Clinical Diagnosis and
Management by Laboratory methods. 23rd ed. St. Louis, MO: Elsevier;
2017:221-243.
18. Langsted A, Freiberg JJ, Nordestgaard BG. Fasting and nonfasting
lipid levels: inuence of normal food intake on lipids, lipoproteins,
apolipoproteins, and cardiovascular risk prediction. Circulation.
2008;118(20):2047-2056.PubMed
19. Nordestgaard BG, Langsted A, Mora S, et al. Fasting is not routinely
required for determination of a lipid prole: clinical and laboratory
implications including agging at desirable concentration cut- points: a
joint consensus statement from the European Atherosclerosis Society and
European Federation of Clinical Chemistry and Laboratory Medicine.
Eur Heart J. 2016;37(25):1944-1958.PubMed
20. Sidhu D, Naugler C. Fasting time and lipid levels in a community- based
population: a cross- sectional study. Arch Intern Med. 2012;172(22):
1707-1710.PubMed
21. US Department of Veterans Aairs, US Department of Defense. VA/
DoD clinical practice guideline for the management of dyslipidemia for
cardiovascular risk reduction. http://www.healthquality.va.gov/guidelines
/CD/lipids. Accessed Jun 28, 2020.
CHAPTER 8 • LiPid disoRdERs 161
https://t.me/med1917
22. Faulkner MA, Hilleman DE, Destache CJ, Mooss AN. Potential inuence
of timing of low- density lipoprotein cholesterol evaluation in patients
with acute coronary syndrome. Pharmacotherapy. 2001;21(9):1055-1060.
PubMed
23. Pitt B, Loscalzo J, Ycas J, Raichlen JS. Lipid levels aer acute coronary
syndromes. J Am Coll Cardiol. 2008;51(15):1440-1445.PubMed
24. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline
for the management of ST- elevation myocardial infarction: a report
of the American College of Cardiology Foundation/American Heart
Association Task Force on Practice Guidelines. J Am Coll Cardiol.
2013;61(4):e78- e140.PubMed
25. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC
Guideline for the Management of Patients with Non-ST-Elevation Acute
Coronary Syndromes: a report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines. J Am Coll
Cardiol. 2014;64(24):e139- e228.PubMed
26. Devaraj S, Remaley AT. Lipids, lipoproteins, apolipoproteins, and other
cardiac risk factors. In: Rifai N, Horvath AR, Wittwer CT, eds. Tietz
Fundamentals of Clinical Chemistry and Molecular Diagnostics. 8th ed.
St. Louis, MO: Elsevier; 2019:391-418.
27. Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults. Executive Summary of e ird Report of e
National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation, And Treatment of High Blood Cholesterol In
Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486-2497.
PubMed
28. Skulas-Ray AC, Wilson PWF, Harris WS, et al. Omega-3 fatty acids
for the management of hypertriglyceridemia: a science advisory from
the American Heart Association. Circulation. 2019;140(12):e673- e691.
PubMed
29. Nikolac N. Lipemia: causes, interference mechanisms, detection and
management. Biochem Med (Zagreb). 2014;24(1):57-67.PubMed
30. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the
concentration of low- density lipoprotein cholesterol in plasma, without
use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499-502.
PubMed
31. Martin SS, Blaha MJ, Elshazly MB, et al. Comparison of a novel
method vs the Friedewald equation for estimating low- density
lipoprotein cholesterol levels from the standard lipid prole. JAMA.
2013;310(19):2061-2068.PubMed
32. Martin SS, Blaha MJ, Elshazly MB, et al. Friedewald- estimated versus
directly measured low- density lipoprotein cholesterol and treatment
implications. J Am Coll Cardiol. 2013;62(8):732-739.PubMed
33. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle
management to reduce cardiovascular risk: a report of the American
College of Cardiology/American Heart Association Task Force on
Practice Guidelines. Circulation. 2014;129(25 suppl 2):S76-S99.PubMed
34. Dhingra R, Vasan R. Lipoproteins and cardiovascular risk. In: Garg A, ed.
Dyslipidemias: Pathophysiology, Evaluation and Management. Totowa, NJ:
Humana Press; 2015:57-65.
35. Wilson DP, Jacobson TA, Jones PH, et al. Use of Lipoprotein(a) in clinical
practice: a biomarker whose time has come. A scientic statement
from the National Lipid Association. J Clin Lipidol. 2019;13(3):374-392.
PubMed
36. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent
vascular events in men and women with elevated C- reactive protein. N
Engl J Med. 2008;359(21):2195-2207.PubMed
37. Kaptoge S, Di Angelantonio E, Lowe G, et al. C- reactive protein
concentration and risk of coronary heart disease, stroke, and mortality:
an individual participant meta- analysis. Lancet. 2010;375(9709):132-140.
PubMed
38. Greenland P, Blaha MJ, Budo MJ, et al. Coronary calcium score and
cardiovascular risk. J Am Coll Cardiol. 2018;72(4):434-447.PubMed
39. Haggerty L, Tran D. Cholesterol point- of- care testing for community
pharmacies: a review of the current literature. J Pharm Pract.
2017;30(4):451-458.PubMed
40. Scolaro KL, Stamm PL, Lloyd KB. Devices for ambulatory and
home monitoring of blood pressure, lipids, coagulation, and weight
management, part1. Am J Health Syst Pharm. 2005;62(17):1802-1812.
PubMed
41. Stone NJ, Robinson JG, Lichtenstein AH, et al. 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. Circulation. 2014;129(25 suppl 2):S1-S45.PubMed
42. Jun M, Perkovic V. Fibrates: risk, benets and role in treating
dyslipidemias. In: Garg A, ed. Dyslipidemias: Pathophysiology, Evaluation
and management. Totowa, NJ: Humana Press; 2015:423-438.
43. Nexletol [package insert]. Ann Arbor, MI: Esperion erapeutics, Inc.;
2020.
162 BASIC SKILLS IN INTERPRETING LABORATORY DATA
https://t.me/med1917
QUICKVIEW | Triglycerides
PARAMETER DESCRIPTION COMMENTS
Common reference ranges
Adults Normal: <150 mg/dL (1.7 mmol/L)
Borderline high: 150–199 mg/dL
(1.7–2.2 mmol/L)
High: 200–499 mg/dL (2.3–5.6 mmol/L)
Very high: ≥500 mg/dL (5.6 mmol/L)
Pediatrics Acceptable:
0–9 yr: <75 mg/dL (0.8 mmol/L)
10–19 yr: <90 mg/dL (1.0 mmol/L)
Borderline high:
0–9 yr: 75–99 mg/dL (0.8–1.1 mmol/L)
10–19 yr: 90–129 mg/dL (1.0–1.5 mmol/L)
High:
0–9 yr: ≥100 mg/dL (1.1 mmol/L)
10–19 yr: ≥130 mg/dL (1.5 mmol/L)
Critical value 500 mg/dL (5.6 mmol/L) High risk of pancreatitis
Inherent activity? Intermediary for other active substances and
stored energy in adipose tissue
Location
Production Liver and intestines From ingested food
Storage Adipose tissue
Secretion/excretion None
Causes of abnormal values
High Excess carbohydrate intake
Genetic defects
Drugs
Alcohol
Low Hypolipidemics
Lifestyle modications
Signs and symptoms
High level
Low level
After event, time to…
Initial elevation Days to weeks Single high-fat meal has major
Peak values Days to weeks Increases with aging
Normalization Days to weeks After diet changes or drug
Causes of spurious results Glycerol, recent high-fat meal, alcohol, lipid
Additional information TGs are not the primary target of therapy unless TGs ≥500 mg/dL (5.6 mmol/L)
Pancreatitis
Eruptive xanthomas
Lipemia retinalis
None
emulsion
SI conversion factor: 0.01129
(mmol/L)
Needed for formation of other
lipids and fatty acids
Tables 8-2 and 8-3
Associated with obesity,
diabetes, and metabolic
syndrome
Statins, niacin, brates, omega-3
fatty acids
Increased risk of ASCVD
effect on TG concentration
within 2 hr
treatment is started
CHAPTER 8 • LiPid disoRdERs 163
https://t.me/med1917
QUICKVIEW | Total Cholesterol
PARAMETER DESCRIPTION COMMENTS
Common reference ranges
Adults
Pediatrics
Critical value Not acutely critical Depends on risk factors, LDL,
Inherent activity? Intermediary for other active substances Needed for cell wall, steroid,
Location
Production Liver and intestines Ingested in diet
Storage Lipoproteins
Secretion/excretion Excreted in bile Also recycled to liver
Causes of abnormal values
High Diet high in saturated fats and trans fats Tables 8–2 and 8–3
Desirable: <200 mg/dL (5.2 mmol/L)
Borderline high: 200–239 mg/dL (5.2–6.2 mmol/L)
High: ≥240 mg/dL (6.2 mmol/L)
Acceptable: <170 mg/dL (4.4 mmol/L)
Borderline high: 170–199 mg/dL (4.4–5.1 mmol/L)
High: ≥200 mg/dL (5.2 mmol/L)
Genetic defects
SI conversion factor:
0.02586 (mmol/L)
TGs, and HDL
and bile acid production
Drugs
Low Hyperthyroidism
Liver disease
Hypolipidemics
Lifestyle modications
Signs and symptoms
High level Tendon xanthomas Increased risk of ASCVD
Low level None Usually considered sign of good
After event, time to…
Initial elevation Days to weeks Single meal has little effect on
Peak values Days to weeks Can increase with aging; does
Normalization Weeks to months After diet changes or drugs
Causes of spurious results Prolonged tourniquet application Causes venous stasis (increase
Additional information Not applicable
Statins, ezetimibe, niacin,
brates, bile acid sequestrants,
PCSK9 inhibitors, bempedoic
acid
health
TC concentration
not change acutely
5%–10%)
164 BASIC SKILLS IN INTERPRETING LABORATORY DATA
https://t.me/med1917
QUICKVIEW | LDL Cholesterol
PARAMETER DESCRIPTION COMMENTS
Common reference ranges
Adults
Pediatrics
Critical value Not acutely critical Depends on risk factors and ASCVD
Inherent activity? Intermediary for other active substances Needed for cell wall, steroid, and bile
Location
Production Liver and intestines Ingested in diet
Storage Lipoproteins
Secretion/excretion Excreted to bile Also recycled to liver
Causes of abnormal values
High Diet high in saturated fats and trans fats, genetic
Low Drugs, hyperthyroidism, liver disease,
Signs and symptoms
High level Atherosclerotic vascular disease, tendon
Low level None Usually considered sign of good health
After event, time to…
Initial elevation Days to weeks Single meal has little effect on LDL
Peak values Days to weeks Can increase with aging; does not
Normalization Weeks to months After diet changes or medications
Causes of spurious
results
Desirable: <100 mg/dL (2.6 mmol/L)
Above desirable: 100–129 mg/dL (2.6–3.3 mmol/L)
Borderline high: 130–159 mg/dL (3.4–4.1 mmol/L)
High: 160–189 mg/dL (4.1–4.9 mmol/L)
Very high: ≥190 mg/dL (4.9 mmol/L)
Acceptable: <110 mg/dL (2.8 mmol/L)
Borderline high: 110–129 mg/dL (2.8–3.3 mmol/L)
High: ≥130 mg/dL (3.4 mmol/L)
defects, hypothyroidism, nephrotic syndrome
hypolipidemics, lifestyle modications
xanthomas
Acute coronary syndrome LDL levels decline within a few hours
SI conversion factor: 0.02586 (mmol/L)
history
acid production
Tables 8-2 and 8-3
8-3
Table
Statins, ezetimibe, niacin, bile acid
sequestrants, PCSK9 inhibitors,
bempedoic acid
Clinical ASCVD
cholesterol concentration
change acutely
of event and may remain low for
several weeks
Additional information LDL may be a target of therapy
Source: Adapted from References 1,12,28,41–43.
Indirect methods are typically used to calculate LDL cholesterol, with the most common
being the Friedewald equation: LDL = TC − HDL − (TGs/5)
This equation cannot be used if TGs >400 mg/dL (4.5 mmol/L) and LDL would need to be
directly measured
9
https://t.me/med1917
Endocrine Disorders
Eva Vivian
OBJECTIVES
After completing this chapter, the
reader should be able to
•
Describe the use of glycated
hemoglobin, fasting plasma glucose,
and oral glucose tolerance tests as
diagnostic tools for type 1 and type 2
diabetes mellitus
•
Explain the major differences
between laboratory values found in
patients with diabetic ketoacidosis
and those in a hyperosmolar
hyperglycemic state
•
Describe the actions of thyroxine,
triiodothyronine, and thyroidstimulating hormone and the
feedback mechanisms regulating
them
•
Given a case description including
thyroid function test results, identify
the type of thyroid disorder and
describe how tests are used to
monitor and adjust related therapy
•
Describe the relationship between
urine osmolality, serum osmolality,
and antidiuretic hormone as they
relate to diabetes insipidus
•
Describe the laboratory tests used
to diagnose Addison disease and
Cushing syndrome
DOI 10.37573/9781585286423.009
e endocrine system consists of hormones that serve as regulators, which stimulate
or inhibit a biological response to maintain homeostasis within the body. Endocrine
disorders oen result from a deciency or an excess of a hormone, leading to an
imbalance in physiologic functions of the body. Usually, negative feedback mechanisms regulate hormone concentrations (Figure9-1). erefore, laboratory assessment of an endocrine disorder is based on the concentrations of a plasma hormone
and integrity of the feedback mechanism regulating that hormone. In this chapter,
the relationship between a hormone (insulin) and a target substrate (glucose) serves
as an example of these concepts. Evaluations of the functions of the thyroid and
adrenal glands are also described. e relationships between vasopressin (antidiuretic
hormone [ADH]) and serum and urine osmolality are used to demonstrate the basis
for the water deprivation test in diagnosing diabetes insipidus.
Glucose serves as the fuel for most cellular functions and is necessary to sustain
life. Carbohydrates ingested from a meal are metabolized in the body into glucose.
Glucose is absorbed from the gastrointestinal (GI) tract into the bloodstream, where
it is used in skeletal muscle and the brain for energy. Excess glucose is stored in the
liver in the form of glycogen (glycogenesis) and is converted in adipose tissue to fats
and triglycerides (lipogenesis). Insulin, which is produced, stored, and released from
β cells of the pancreas, facilitates these anabolic processes. e liver, skeletal muscle,
brain, and adipose tissue are the main tissues aected by insulin. To induce glucose
uptake, insulin must bind to specic cell- surface receptors. Most secreted insulin is
taken up by the liver, while the remainder is metabolized by the kidneys.
In the fasting state, insulin levels decrease, resulting in an increase in glycogen
breakdown by the liver (glycogenolysis) and an increase in the conversion of free
fatty acids to ketone bodies (lipolysis).1 When glucose concentrations fall below
70mg/dL, an event known as hypoglycemia occurs, resulting in the release of glucagon by the pancreatic α cell. Glucagon stimulates the formation of glucose in the
liver ( gluconeogenesis) and glycogenolysis. Glucagon also facilitates the breakdown
of stored triglycerides in adipose tissue into fatty acids (lipolysis), which can be used
for energy in the liver and skeletal muscle. In addition to glucagon secretion, hypoglycemia leads to secretion of counterregulatory hormones such as epinephrine, cortisol, and growth hormone. Epinephrine release in response to hypoglycemia results
in neurogenic symptoms such as sweating, palpitations, tremulousness, anxiety, and
hunger. Glucagon and, to a lesser degree, epinephrine promote an immediate breakdown of glycogen and the synthesis of glucose by the liver. Cortisol increases glucose
levels by stimulating gluconeogenesis. Growth hormone inhibits the uptake of glucose
by tissues when glucose levels fall below 70 mg/dL.
In individuals without diabetes, once plasma glucose concentrations exceed
180 mg/dL (the renal threshold), renal glucose reabsorption is saturated and glucose starts to appear in the urine. In individuals with hyperglycemia, large amounts
of glucose may be excreted into the urine. However, in diabetes mellitus (DM), the
renal glucose threshold may increase up to 240 mg/dL, causing reabsorption of more
glucose, which further contributes to hyperglycemia.
1
1
165
Соседние файлы в папке Библиотека им академика М.И. Перельмана