NA offers additional benefits to the lipid profile, typically lowering LDL cholesterol by 20%, triglycerides by 15%, and lipoprotein(a) by 15%.15
Monitor all forms of NA with liver enzymes, blood glucose, and uric acid because treatment can elevate these markers.
Give NA preparations extra scrutiny. The general caveats about quality and bioavailability apply especially to NA. Nonprescription products on the market that contain nicotinamide and inositol hexanicotinate are advertised as “no-flush” niacin because they do not cause cutaneous side effects, but they also have no lipid benefits.
Cost. NA is relatively inexpensive, and good-quality sustained-release products such as Endur-acin (Endurance Products, Tigard, Ore) can be purchased OTC for 12 cents per 500-mg tablet or a daily cost of 24 to 36 cents.16
Sustained-release NA is also available by prescription (Niaspan, Kos Pharmaceuticals, Cranbury, NJ), but it is considerably more expensive ($1.98 per 500-mg tablet, or $3.96 to $5.94 daily) and has not been shown to be more effective or better tolerated than the better OTC products.16
JUDY’S CASE
RAISING HDL WITHOUT DRUGS
Judy’s lipid abnormalities would benefit from a supplement of pantethine (300 mg thrice daily) or NA (1,000 mg thrice daily of plain/quick release or 500 mg twice daily of sustained release to reduce flushing side effects).
Her greatest risk with her current lipid levels is low HDL, and the best agent to raise these levels is NA.
Pantethine also raises HDL and selectively improves the HDL-2 subfraction, which is most cardioprotective. Both supplements also improve the other lipid abnormalities.
In addition, referral to a dietician for detailed instruction in food choices and preparation may be useful.
Pharmacologic therapies
Hormone replacement therapy (HRT) is no longer recommended to prevent CVD and should be given only for menopausal symptoms during the perimenopausal years—despite the fact that estrogen has been shown to raise HDL cholesterol by 8% in postmenopausal women.17
Estrogens increase HDL by increasing production of apoA-1, the main lipoprotein in HDL, and by decreasing HDL catabolism by inhibiting hepatic lipase. The 17-hydroxyprogesterone component of HRT given to women with an intact uterus to prevent endometrial cancer has no significant lipid effects.
Paradoxically, the increased CVD risk found in the HRT arm of the Women’s Health Initiative17 was in the face of improved HDL (8%) and LDL (–14%) cholesterol and appeared to be the result of increased thrombotic events.
Further analysis of Women’s Health Initiative data showed that women who were still within 10 years of menopause actually did experience a reduction in CVD risk. That observation, along with some primate research on HRT, suggests that the risk or benefit of HRT with respect to CVD may be a matter of timing. See “Emerging hypothesis may explain estrogen paradox”
Emerging hypothesis may explain estrogen paradox
At the 2004 American Heart Association meeting, Dr. Thomas Clarkson, who has conducted primate research on hormone replacement therapy (HRT) and the risk of cardiovascular disease (CVD), described the emerging hypothesis that may explain the HRT paradox of increased CVD risk despite evidence of benefit in observational studies.21
Estrogen is a potent upregulator of matrix metal-loproteases. These proteolytic enzymes are a normal constituent of the endometrium and important in its remodeling with each menstrual cycle. Matrix metal-loproteases are also found in the fibrous cap that seals off the necrotic core of an advanced atheroma from the vascular lumen. Most perimenopausal women have enjoyed estrogen’s protective effect throughout their reproductive years and thus have developedlittle advanced atherosclerotic disease.
Ten or more years past menopause, however, clinically significant atherosclerotic lesions often develop in women who have been without the protection of estrogen. If estrogen is added at this stage, it causes increased matrix metalloprotease activity in the fibrous cap of any atheroma. This proteolytic activity can destabilize the fibrous cap, allowing necrotic core material to come in contact with the bloodstream.
This necrotic material is highly thrombogenic and stimulates clot formation in the vascular lumen. Clarkson demonstrated this process in research on perimenopausal and postmenopausal primates.
This hypothesis will soon be tested in a clinical trial in humans; CVD risk is expected to decrease by 50% to 70% in women who have taken HRT continuously from perimenopause.
Statins and other HDL-modifying drugs
The statins are a first choice for LDL reduction, but lead to only modest increases (4%–10%) in HDL levels.18 Fibric acid derivatives are somewhat more effective; they lead to increases in HDL of 6% to 18%. Both types of drugs are considerably more expensive than OTC NA and not as effective at raising HDL.
Combining statins with other agents that raise HDL has been tried: The NA–statin combination can be effective in managing dyslipidemias of both LDL and HDL. Fibric acid derivatives should not be used with statins because of the increased risk of serious myopathies.18