Pharmacotherapy options are effective in patients suffering from mild-to-moderate PAD and intermittent claudication (Figure 2). Antithrombotic therapy (aspirin or clopidigrel [Plavix]) is a simple and low-cost intervention that provides a 23% risk reduction.
There are two FDA-approved medications for treatment of intermittent claudication. Cilostazol (Pletal) has been shown to increase pain-free walking distance by 50%. Cilostizol may not be used in individuals with heart failure or those with an ejection fraction <40%. The second medication is pentoxifylline [Pentopak, Pentoxil, Trental].12
In addition to antithrombotic therapy, treatment is also aimed at comprehensive risk reduction by smoking cessation and tight lipid and glycemic control. Revascularization by either endovascular or surgical treatment is the final treatment option. Several emerging adjuvant treatments are currently under investigation, including the use of growth factor, gene therapy and stem-cell transplantation to promote local tissue growth.13-15 Cell-based cardiac repair offers new hope for the treatment of PAD, CAD and heart failure.
Elevated triglycerides (TG) and low HDL are the hallmark lipid values seen in metabolic syndrome. In these patients, there is often small, dense LDL; a non-HDL (total cholesterol minus HDL) level is a more accurate reflection of the total number of atherogenic particles. The non-HDL goal is defined as 30 points higher than the identified LDL goal. An additional test to understand the total atherogenic burden is an apolipoprotein B (ApoB).
The desired ApoB level for a high-risk patient is <80 mg/dL. Lifestyle modification remains the first and best treatment strategy, as the main causes of mixed dyslipidemia are overweight, poor diet and low level of physical activity. Interventions aimed at all three factors will result in lower TG levels and a slow but progressive increase in HDL.
For persons who present with a significant family history of early CAD or stroke, a lipoprotein (Lp)(a) level will affirm the level of risk; if elevated, family members should be counseled to get screened. In individuals with elevated Lp(a), the goal is to decrease LDL (at least <100 mg/dL and more desirably <70 mg/dL).
There is some disagreement over whether Lp(a) is a risk marker only or a treatment target as well. Individuals with an elevated Lp(a) are at higher risk of embolic events (i.e., stroke or MI), and aspirin therapy is usually indicated in these cases. Niacin therapy will reduce Lp(a) levels, but it is not clearly understood whether treating Lp(a) values will effect outcomes. Niacin may be therapeutic because of its beneficial effects on TG, LDL, and HDL. Advanced lipid testing is an evolving science.
Researchers are now looking at medications found to increase HDL. One such drug class is the cholesterylester transfer protein (CETP) inhibitors. The assumption is that increasing HDL may reduce CVD events. A few years ago, testing of torcetrapib was discontinued due to BP elevations observed in the treatment arm. Dalcetrapib and anacetrapib are two new CETP inhibitors currently in development that have not been found to increase BP readings. However, the question of whether raising HDL is beneficial remains unanswered.16
Many dietary supplements can have a beneficial effect on health. Natural alternatives can be safe when monitored and managed by a primary-care provider (PCP). Lovaza (omega-3-acid ethyl esters) is a prescription medication with dose of 900 mg per capsule of eicosapentaenic acid and docosahexaenoic acid, the active ingredients that affect lipids. When considering an OTC option, look for an alternative with the same active ingredient strength.
Red yeast rice (RYR) is another popular supplement used to treat dyslipidemia, especially among the small percentage of patients that cannot tolerate a statin medication due to myalgias. The active ingredient in RYR is monacolin K, an equivalent to lovastatin (Altocor, Altoprev, Mevacor). A full dose of RYR 600 mg b.i.d. is equal to lovastatin <10 mg.
RYR contains other monacolins that may further inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. The monacolins are thought to be less likely to deplete such mevalonate metabolites as ubiquinone or coenzyme Q10 and guanosine triphosphate binding protein, which are believed to mediate statin-induced muscle injury. When paired with lifestyle changes, RYR has been shown to lower LDL up to 27%.17
Patients must be cautious when taking RYR, as hepatotoxicity is a concern; liver function tests (LFTs) should be monitored regularly. Myopathy and rhabdomyolysis, similar to that seen with statins, have been reported in persons using RYR.
Several OTC preparations of niacin (vitamin B3) work to reduce LDL and TG and increase HDL. Immediate, extended-release (Niaspan), and sustained-release preparations are available. The OTC niacin preparations will cause a flushing response similar to that seen with Niaspan. This flushing can be thought of as an expected therapeutic response. Regular LFT monitoring is recommended with the use of these medications.
Many OTC therapies claim to improve lipid levels, but plant stanols and sterols have been shown to lower LDL up to 15% with recommended dosing.18 Several types of preparations are available, including pills, yogurt and spreads.
Obstructive sleep apnea
OSA is a common disorder that affects 25% to 35% of obese individuals.19 The condition is characterized by recurring episodes of limited airflow during sleep as a result of upper airway collapse. This alteration in airflow often results in oxygen desaturation, causing poor sleep, excessive daytime somnolence, and a host of metabolic, inflammatory, neuropsychiatric, respiratory and cardiovascular disorders.
OSA is often under-recognized and under-diagnosed. At the time of diagnosis, the average OSA patient has been symptomatic for approximately seven years and has visited his or her PCP approximately 17 times.20
Inconvenient diagnostic testing is a one explanation for the high number of undiagnosed cases of OSA. The polysomography single night test has traditionally been considered the only diagnostic test for OSA. However, this test can be difficult for some patients due to limited accessibility to a sleep lab, cost and the patient’s inability to fall asleep in the lab setting.