Term
| how can insulin resistance lead to atherosclerosis? |
|
Definition
| insulin resistance contributes to HTN, obesity, hyperinsulinemia, DM, hypertriglyceridemia, small dense LDL, and low LDL - all of which accelerate atherosclerosis. |
|
|
Term
| what is metabolic syndrome? |
|
Definition
| 3 of the following criteria: 1) abdominal obesity: waist circumference > 102 cm/40 in for men and > 88 cm/35 in for women. 2) TG levels > 150 mg/dl. 3) HDL < 40 mg/dl for men and < 50 for women. 4) BP > 130/85 mm/Hg. 5) fasting glucose > 110 mg/dl. |
|
|
Term
| what characterizes lipid in a specifically DM2 pt? |
|
Definition
| LDL is smaller and denser (class B as opposed to class A, which is larger) but not elevated much higher than normal, total TGs and VLDLs are elevated (all are Apo B). HDL is reduced (Apo A1). |
|
|
Term
| what are the mechanisms relating insulin resistance and dyslipidemia in DM? |
|
Definition
| insulin resistance keeps FFAs from being incorporated into adipose cells, shunting them to the liver, which converts them to an excess of TGs and VLDLs (creates a fatty liver). these VLDLs have more TGs attached to them than normal which are then transferred by cholesterol ester transfer protein (CETP) to HDL. the TG-heavy HDL molecules then degrade by the kidney (this is why TGs are up and HDLs are down in DM2 pts). the same TG-heavy VLDLs also transfer TGs to LDL via CETP, creating small dense LDLs (SDLDL). these smaller LDLs are now even more able to diffuse into vascular walls and set up oxidation/atherogenesis. |
|
|
Term
| what is familial combined hyperlipidemia? |
|
Definition
| a common disorder where pts have increased LDL and VLDL w/increased Apo B secretion (sets up high TG, low HDL, small dense LDL environment) |
|
|
Term
| what is familial hypercholesterolemia? what drug can be used to treat this? |
|
Definition
| absent (homozygous) or 50% reduced (heterozygous) LDL receptors = LDL can't get back into the liver = elevated LDLs. high statin doses can help with this as they upregulate LDL receptors on the liver. |
|
|
Term
| what is familial dysbetalipoproteinemia? |
|
Definition
| atherogenic accumulation of VLDL and ILDL remnants |
|
|
Term
| what is hyperchylomicronemia? |
|
Definition
| high TG content VLDLs, which become enlarged and stuck in brain, pancreatic ducts = organ damage via disruption of blood flow. this may occur w/insulin deficiency as lipoprotein lipase requires insulin to function. |
|
|
Term
| does just the presence of DM in a pt put them at a higher risk for atherosclerotic disease? |
|
Definition
| yes - the same level of risk as if they have carotid artery disease (bruit), peripheral arterial disease, or abdominal aortic aneurysm (> 20% risk of a major coronary event in the next 10 years). |
|
|
Term
| what should the LDL target level be for pts at a high risk of a CV event (includes DM pts)? |
|
Definition
| < 100 mg/dl, but if they have already had a CV event it needs to be < 70 mg/dl (may require combination therapy). |
|
|
Term
| what are other CVD risk factors? are there any situations where one of these risk factors might be negated? |
|
Definition
| smoking, HTN, family hx of premature heart disease (M: < 55/F: < 65), and age (M: < 45/F: < 55). if HDL is > 60, this negates one risk factor. |
|
|
Term
| what is non HDL cholesterol (NHC)? what is the target level for this in DM pts? |
|
Definition
| HDL does not contain Apo B, but VLDL/ILDL/LDL do, and they collectively make up the non HDL cholesterol. the target NHC level for DM pts is their LDL level + 30 mg/dl (so 130 for high risk pts). |
|
|
Term
| when is the only time that another high lipoprotein level besides LDL needs to be lowered first? |
|
Definition
| if TGs are > 500, this needs to be addressed first - otherwise lowering LDL is the first priority. |
|
|
Term
| how do resins such as cholestyramine address dyslipidemia? |
|
Definition
| cholestyramine blocks uptake of dietary cholesterol causing a cholesterol deficiency which the liver responds to by increasing LDL receptors - decreasing circulating LDLs. the major action is on LDL, but resins also increase HDL by 5%. they have been also been shown to decrease blood glucose. |
|
|
Term
| how does nicotinic acid address dyslipidemia? |
|
Definition
| nicotinic acid raises HDL and lowers TG (up to 50%). LDL is also lowered, but this is not the major action. it can also raise blood glucose, so it is not ideal in all DM pts. |
|
|
Term
| how do fibrates address dyslipidemia? |
|
Definition
| fibrates act through PPAR alpha to lower TGs and raise HDL. |
|
|
Term
| how do statins address dyslipidemia? what is the rule of 6's? |
|
Definition
| they lower cholesterol and LDL (up to 60% - dose dependent). the rule of 6's: the first dose gives a 30% reduction in LDL and subsequent dosing will consistently give 6% reductions. |
|
|
Term
| can statins prevent primary and secondary CV events? |
|
Definition
|
|
Term
| what is the most potent statin in terms of LDL levels? |
|
Definition
| rosuvastatin but atorvastatin is also highly potent |
|
|
Term
| other than LDL levels, how can CV risks be monitored specifically once pts are on statin levels? |
|
Definition
| carotid artery intimal medial thickness |
|
|
Term
| what is the association between hypertriglyceridemia and CHD? |
|
Definition
| higher: accumulation of chylomicron remnants, VLDL remnants, generation of small dense LDL (class B), association w/low HDL (destroyed scavenging ability), and increased coagulability (increased plasminogen activator inhibitor (PAI-1), increased factor VIIc, and activation of prothrombin to thrombin) |
|
|
Term
| what does PPAR alpha (peroxisome proliferator-activated receptor alpha) do? how can this be harnessed in tx of dyslipidemia? |
|
Definition
| PPAR alpha increases FFA oxidation, reducing TG formation. drugs such as the fenofibrates increase this action. |
|
|
Term
| what are the therapeutic actions of fish oil? |
|
Definition
| omega-3 FFAs lower TGs, raise HDL, and have anti-inflammatory/anti-arrhythmic effects via the active ingredients DHA/EPA (need at lesat 4 mg). |
|
|
Term
| what is the therapeutic effect of CETP inhibitors? |
|
Definition
| CETP reduces HDL, increases TGs and increases small dense LDL via unloading TG-heavy VLDLs onto HDLs/LDLs. inhibiting this enzyme lowers these effects. |
|
|
Term
| what is ezetimibe and why is it commonly combined w/statins? |
|
Definition
| ezetimibe reduces cholesterol absorption in the gut and the statins reduce cholesterol synthesis in the liver = reduction of cholesterol through 2 pathways |
|
|
Term
| what ADRs are associated w/statins? |
|
Definition
| decreased mental acuity, liver issues, and muscle weakness (dose dependent) |
|
|
Term
| what are 2 markers used to determine CV risks? |
|
Definition
| CRP: if over 2, the pt is at risk (proinflammatory). lipoprotein (a): a part of some LDL molecules which if in high levels can be even more thrombogenic. |
|
|
