Lipid abnormalities

This chapter addresses (1) the mechanisms, antioxidant defences and consequences in relation to free-radical production in the inflamed rheumatoid joint (2) lipid abnormalities in RA (3) the potential contribution of ox-LDL to RA (the role of ox-LDL in coronary heart disease is discussed in Chapters 2 and 3 and will not be fully discussed here) and (4) the therapeutic aspects of chain-breaking antioxidant interventions in RA. 

Lipid abnormalities are associated with a wide spectrum of pathological conditions. In particular, recent advances have been made in understanding the role of lipoproteins in coronary heart disease (Davies and Woolf, 1993). However, included within the spectrum of diseases associated with perturbations of lipid metabolism are a number of musculoskeletal problems including inflammatory polyarthritis, tenosynovitis, osteoporosis and bone cysts. 

Conditions that may produce lipid abnormalities (such as those listed in Table 9-3) should be screened for using appropriate tests. If present, these conditions should be properly addressed. 

Compared with monotherapy, combination therapy is relatively unstudied in terms of the effects on CHD event reduction and may reduce patient compliance through increased side effects and increased costs. When used appropriately and with proper precautions, however, they are effective in normalizing lipid abnormalities, particularly in patients who cannot tolerate adequate doses of statin therapy for more severe forms of dyslipidemia. 

Institute appropriate pharmacotherapy based on lipid abnormality. Obtain appropriate baseline labs to monitor for adverse drug effects. Assess potential disease and drug interactions that may affect choice or intensity of pharmacotherapy. 

Skoczynska A, Smolik R, Jelen M. 1993. Lipid abnormalities in rats given small doses of lead. Arch Toxicol 67 200-204. 

Henderson DC, Cagliero E, Gray C, Nasrallah RA, Hayden DL, Schoen-feld DA et al. Clozapine, diabetes melli-tus, weight gain, and lipid abnormalities A five-year naturalistic study. Am J Psychiatry 2000 157(6) 975—981. 

After a lipid abnormality is confirmed, major components of the evaluation are the history (including age, gender, and, if female, menstrual and estrogen replacement status), physical examination, and laboratory investigations. 

K10. Keilani, T., Schlueter, A., Levin, M. L., and Battle, D. C., Improvement of lipid abnormalities associated with proteinuria using fosinopril, an angiotensin-converting enzyme inhibitor. Ann. Intern. Med. 118, 246-254 (1994). 

Initial therapy Ascertain that lipid levels are consistently abnormal before instituting fenofibrate therapy. Make every attempt to control serum lipids with appropriate diet, exercise, weight loss in obese patients, and control of any medical problems (eg, diabetes mellitus, hypothyroidism) that are contributing to the lipid abnormalities. If possible, discontinue or change medications known to exacerbate... 

Bexarotene is a member of a subclass of retinoids that selectively activate rehnoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of rehnoic acid receptors (RARs). After oral administration bexarotene is rapidly absorbed. Bexarotene is thought to be eliminated primarily through the hepatobiliary system. It is approved for the treatment of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Adverse events possibly related to treatment are lipid abnormalities, hypothyroidism, rash, and blood dyscrasias. 

Lipid abnormalities are a major adverse effect of HIV protease inhibitors (160). In a 48-week comparison with nelfinavir, atazanavir did not significantly increase total cholesterol, fasting LDL cholesterol or triglyceride concentrations (+6.8%, -7.1%, +1.5% respectively), while the respective concentrations rose by 28%, 31%, and 42% in those who took nelfinavir. The incidence of grade 1—4 lipodystrophy was infrequent in both groups, but this endpoint was poorly defined in this study. 

Lafeuillade A, Jolly P, Chadapaud S, Hittinger G, Lambry V, Philip G. Evolution of lipid abnormalities in patients switched from stavudine- to tenofovir-containing regimens. J Acquir Immune Defic Syndr 2003 33 544-6. 

Micheh V, Carosi G Resistance and Dosage Adapted Regimens Study Group of the MASTER Cohort. Lipid abnormalities in HIV-infected patients are not correlated with lopinavir plasma concentrations. J Acquir Immune Defic Syndr 2004 35(3) 324-6. 

Yamamoto, A., et al. 1991. Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res 283 219. 

Fulmer, A.W., and G.J. Kramer. 1986. Stratum corneum lipid abnormalities in surfactant-induced dry scaly skin. J Invest Dermatol 86 598. 

Most cystic acne patients respond to 1-2 mg/kg, given orally in two divided doses daily for 4-5 months. If severe cystic acne persists following this initial treatment, after a period of 2 months, a second course of therapy may be initiated. Common adverse effects resemble hypervitaminosis A and include dryness and itching of the skin and mucous membranes. Less common side effects are headache, corneal opacities, pseudotumor cerebri, inflammatory bowel disease, anorexia, alopecia, and muscle and joint pains. These effects are all reversible on discontinuance of therapy. Skeletal hyperostosis has been observed in patients receiving isotretinoin with premature closure of epiphyses noted in children treated with this medication. Lipid abnormalities (triglycerides, HDL) are frequent their clinical relevance is unknown at present. 

Depression and Diabetes Mellitus. Patients with chronic medical illness have a high prevalence of major depressive disorder [59], Depression may be three times more prevalent in the diabetic population when compared with its occurrence in nondiabetic individuals [60], In addition, microalbuminuria, hypertension, and hyperinsulinemia are another three independent risk factors for cardiac disease in non-insulin-dependent diabetes mellitus (NIDDM) [61], Nosadini et al. showed that peripheral insulin resistance, hypertension, microalbuminuria, and lipid abnormalities are associated with NIDDM [61], Further, Helkala et al. determined that cognitive and memory dysfunction are associated with NIDDM and explored the disease s relationship with depression, metabolic control, and serum lipids. The results showed that the NIDDM patients had impaired control of their learning processes [62], Obviously, future research examining the causal relationship of depression to the onset on diabetes and the effect of depression on the natural course of diabetes is needed [60]. 

Although hyperlipidemia may be partly reversed by the increase of plasma oncotic pressure with dextran infusion, decreased albumin and plasma oncotic pressure cannot fully explain nephrotic hyperlipidemia. In analbuminemic rats, lipid changes are different from those in nephrotic subjects (D4). There may be a direct causal link between proteinuria and lipid abnormalities because a 1 -acid glycoprotein isolated from urine of nephrotic patients may correct the impaired lipolysis of nephrotic rats (SI 6, K12). Thus, impaired lipoprotein metabolism may be caused by the loss of some regulatory substance into urine due to increased glomerular permeability. 

W2. Walker, W. G., Relation of lipid abnormalities to progression of renal damage in essential hypertension, insulin-dependent and non-insulin-dependent diabetes mellitus. Miner. Electrolyte Metab. 19, 137-143 (1993). 

In a related study, streptozotocin-induced diabetic rats were treated with pyridox-amine, vitamin E, and enalapril (7V-(l-[ethoxycarbonyl -3-phcny I propyl)-Ala-Pro), an AGE/ALE inhibitor, an antioxidant, and an ACE-inhibitor, respectively.598 Diabetic hyperglycaemia was accompanied by severe dyslipidaemia. Treatment with pyridoxamine was the most effective in reducing lipid abnormalities and in retarding nephropathy, retinopathy, and protein modification. Vitamin E was the next most effective treatment in retarding nephropathy, but did not affect retinopathy or AGE/ALE formation. Enalapril normalised blood pressure and retarded nephropathy and the accumulation of CML in the kidney, but did not affect dyslipidaemia and retinopathy. Thus pyridoxamine is the most effective therapy overall. 

Analysis of I-cell patient glycosphingolipids reveals elevations in trihexosylceramide (GL-3) and the ganglioside GM3 (Fig. 17-3) but not the massive accumulation associated with the glycosphingolipidoses. In the spleen, the only apparent lipid abnormality is an increase in the level of GMj. The brain has normal levels of gan-gliosides, apart from a small increase in GM3 and... 

Trihydroxy- Bryonia alba (Cucurbitaceae) [root] (ALL-DB mouse) Lipid abnormalities elevated... 

Correction of blood lipid abnormalities offers scope for a major impact on cardiovascular disease. Drugs play a significant role and have a variety of modes of action. Dietary and lifestyle adjustment are components of overall risk prevention. 

Much of the work of lipid clinics is taken up with attending to multiple interacting risk factors such as hypertension, diabetes, thyroid disease and smoking, as well as to the lipid abnormality. 

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