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E-CASE #16-B
Kathryn Kovacs, M.D.
October 1-5, 2001
48 yo male with no family hx or personal hx of CAD, a BMI of 30 kg/mg
2 (waist circumference of 44 in.) and BP of 140/90 comes in
for a PE prior to new employment. He has no significant PMHx, does not
smoke but has "a few beers on weekends". He does not take any medications
or vitamins. He is not following any particular diet and rarely exercises.
PE is unremarkable.
He has a fasting blood glucose of 142 mg/dL and his fasting lipid panel
is as follows:
| Total cholesterol |
240 mg /dL |
| Triglycerides |
390 mg/dL |
| LDL-cholesterol |
124 mg/dL |
| HDL-cholesterol |
30 mg/dL |
Given the increasing prevalence of the above patient profile as seen
in the primary care office setting, and the timely publication of the
NCEP III guidelines, it seems prudent to educate ourselves further about
this condition. What is the underlying unifying diagnosis present in
this case?
Identifying patients with the metabolic syndrome (previously known as Syndrome
X):
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Diagnostic criteria not definitively established.
-
Unclear whether it is one disease or a cluster of associated risk
factors that appear with excessive weight gain and aging.
-
Another confounder in the diagnosis is that the clinical features
of the syndrome are continuous variables, i.e. glucose intolerance,
obesity, insulinemia, dyslipidemia and hypertension.
-
Nevertheless, given the high risk of developing CAD (at any given
level of LDL cholesterol) in these individuals, it is important to
identify patients at risk of developing this syndrome, as well as
those that have it.
NCEP III recommendations to aid
in the clinical diagnosis:
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Central obesity with waist circumference > 40 in men or > 35
in. in women.
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Triglyceride level ³ 150 mg/dL
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Low HDL cholesterol level, e.g. < 40 mg /dL in men and < 50
mg /dL in women
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Blood pressure ³ 130/ ³ 85 mm Hg
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Fasting serum glucose ³ 110 mg/dL
Of note, a number of procoagulant factors have been identified in patients
with the metabolic syndrome, including increased plasminogen activator inhibitor-1,
hyperfibriongenemia, and increased concentrations of factor VII.
Treatment- Based on three therapeutic
objectives
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Suppression of insulin resistance
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Correction of dylipidemia
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Control of individual risk factors
Lifestyle modification (diet and exercise)
is most effective method to suppress insulin resistance. Diet limited in
carbohydrates as well as saturated fats may be preferred as the former can
increase TG levels if large percentage of caloric intake. If lifestyle modification
fails, then medications are used to increase insulin sensitivity. Metformin
has the advantage of promoting weight loss and both metformin and the thiazolidinediones
can decrease plasma TG levels.
Fibrates (gemfibrozil and fenofibrate)
and niacin are the drugs of choice
in treating the most common dyslipidemias in these patients, i.e. elevated
TG and low HDL, unless they have very high LDL levels requiring a statin.
Both fibrates and niacin lower TG levels, gemfibrozil to a greater degree,
but unlike niacin, it can also increase the LDL level (Guyton et al). Statins
have some TG level lowering ability, less than both fibrates and niacin,
but if a statin is to be used, atorvastatin has shown the greatest reduction
in TG levels (Wolfenbuttel et al). Omega 3 polyunsaturated FA have also
been shown to decrease serum TG levels and are generally well tolerated.
Both fibrates and niacin raise HDL to a greater degree than statins, with
niacin providing the greatest increase in HDL levels. Many patients have
difficulty tolerating therapeutic doses of niacin secondary to flushing,
but the long acting form, Niaspan, appears to be better tolerated (Guyton
et al).
The combination of a fibrate and a statin
may be the best approach in treating those individuals with elevated LDL,
TG and low HDL but this combination must be used with caution due to the
increased risk of myopathy. The latter was most prominent when cerivastatin
(Baycol) was used with gemfibrozil, prior to the former being pulled from
the market due to reported cases of rhabdomyolysis.
In managing other coexisting risk factors there are important points
to consider. Many of these patients are diabetic and niacin is may be
associated with worsening glycemic control in these individuals. A fibrate
is generally the preferred agent. In patients with HTN and insulin resistance,
ACE inhibitors are a preferred choice
given both the increased insulin sensitivity they provide as well as the
nephroprotective and cardioprotective benefits they afford. The use of
beta blockers and diuretics have been associated with adverse effects
on the lipid profile, with nonselective beta blockers increasing serum
TG levels 20-50% and B1 selective agents increasing them 15-25%. The thiazide
diuretics are also implicated in raising serum TG levels, but only at
higher doses (> 50 mg qd) and to a less degree than that seen with
the beta blockers. Diuretics are also associated with increasing insulin
resistance in some individuals. ASA
should be used to reduce the prothrombotic state and has the added benefit
of decreasing the short-acting niacin, if taken 30 minutes beforehand.
References
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National Cholesterol Education Program Expert Panel. 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). JAMA. 2001;
285: 2486-2497.
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Guyton JR, Blazing MA, Hagar J, Kashyap ML, Knopp RH, McKenney JM,
Nash DT, Nash SD. Extended-release niacin vs. gemfibrozil for the
treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil
Study Group. Arch Intern Med. 2000 Apr 24: 160 (8): 1177-84.
- Wolffenbuttel BH, Mahla G, Muller D, Pentrup A, Black DM. Efficacy
and safety of a new cholesterol synthesis inhibitor, atorvastatin, in
the comparison with simvastatin and pravastatin, in subjects with hypercholesterolemia.
Neth J Med 1998; Apr: 52 (4): 131-7
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