Low density lipoprotein natural history, prognosis and complications
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Rim Halaby, M.D. [2]
Overview
The natural history and prognosis of patients with elevated LDL are directly related to the complications associated with dyslipidemia. The decreased affinity of small dense LDL particles for LDL receptors has been postulated to be the cause of atherogenic properties of small dense LDL. They are more prone to oxidation,[1] have higher affinity to vascular proteoglycans,[2] and are preferentially phagocytosed by macrophages via scanvenger proteins that promote atherosclerosis.[3] Accordingly, high LDL concentrations are not only associated with the initiation of atherogenesis, but also with the gradual worsening of atherosclerosis.[4] Patients with elevated plasma LDL who are left untreated often develop atherosclerosis and cardiovascular disease (CVD). More importantly, the risk of CVD further increases when dyslipidemia is associated with other cardiovascular risk factors, such as diabetes mellitus, hypertension, and low HDL, which are often concomitantly present among patients with dyslipidemia.[5][6]
- Dyslipidemia caused by elevated LDL is a major risk factor for coronary artery disease (CAD) and often regarded as a prerequisite.[7] There is a direct association between cardiovascular death and duration of elevated plasma LDL levels.[8] An increase of LDL by 10 mg/dL is associated with a 12% increase in CVD risk in both genders.
- LDL concentration is also associated with a significant increase in the incidence of stroke
- The Framingham study demonstrated that elevated LDL is associated with non-CAD-death among both genders.[6]
- Stampfer and colleagues (1996) also revealed in a nested case-control study that elevated triglyceride component within LDL has independent association with myocardial infarction (MI). Clinically, the study revealed that non-fasting triglyceride levels is an independent predictor of MI, especially when combined with elevation of total cholesterol.
- Elevated LDL is associated with the development of peripheral arterial disease (PAD)
- However, the occurrence of isolated small dense LDL phenotype is quite uncommon. It is usually part of multiple metabolic disturbances, including low HDL, elevated triglyceride levels, increased waist-to-hip ratio, and insulin resistance.
References
- ↑ Tribble DL, Holl LG, Wood PD, Krauss RM (1992). "Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size". Atherosclerosis. 93 (3): 189–99. PMID 1590824.
- ↑ Chapman MJ, Guérin M, Bruckert E (1998). "Atherogenic, dense low-density lipoproteins. Pathophysiology and new therapeutic approaches". Eur Heart J. 19 Suppl A: A24–30. PMID 9519339.
- ↑ Vergès B (2005). "New insight into the pathophysiology of lipid abnormalities in type 2 diabetes". Diabetes Metab. 31 (5): 429–39. PMID 16357786.
- ↑ Grundy SM (1997). "Small LDL, atherogenic dyslipidemia, and the metabolic syndrome". Circulation. 95 (1): 1–4. PMID 8994405.
- ↑ Stamler J, Vaccaro O, Neaton JD, Wentworth D (1993). "Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial". Diabetes Care. 16 (2): 434–44. PMID 8432214.
- ↑ 6.0 6.1 Gordon T, Kannel WB, Castelli WP, Dawber TR (1981). "Lipoproteins, cardiovascular disease, and death. The Framingham study". Arch Intern Med. 141 (9): 1128–31. PMID 7259370.
- ↑ Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM; et al. (2011). "Heart disease and stroke statistics--2011 update: a report from the American Heart Association". Circulation. 123 (4): e18–e209. doi:10.1161/CIR.0b013e3182009701. PMID 21160056.
- ↑ Rader DJ, Cohen J, Hobbs HH (2003). "Monogenic hypercholesterolemia: new insights in pathogenesis and treatment". J Clin Invest. 111 (12): 1795–803. doi:10.1172/JCI18925. PMC 161432. PMID 12813012.