2 The HistoryMrs TZ 60yo, takes the following medications on a regular basis.Moduretic 50/5mg (Amiloride/Hydrochlorothiazide) 1 M (commenced 3 weeks ago)Norvasc (Amlodipine) 10mg 1 DPlavix (Clopidogrel) 75mg 1 D
4 Estimating LDL Using Friedewald equation: LDL = TC – HDL – TG mmol/L 2.19= 7.6 – 0.7 – 3.3Mrs TZ LDL = 5.4 mmol/LLDL > 5 mmol/L excessive even in the absence of risk factors Foundation of Oz Guidelines:LDL > 3 risk of CVD
5 Medications which affect lipid levels Antihypertensive medicationsThiazide & loop diuretics VLDL & LDLs blockersespecially Propanolol – HDL & total CH/HDL CH ratioOthers include:Hepatic microsomal enzyme inducersOCsGCsA lg # of meds can adversely affect serum lipid & lipoprotein [ ]s:Oral contraceptivesOestrogen causes a slight increase in hepatic production of VLDL and HDL, reduces serum LDL levels in post menopausal womenProgestogen increases LDL and reduces serum HDL and VLDLCorticosteroidsGlucocorticoids shown to increase serum CH and TGs by elevating LDL, and VLDL to a lesser extentmore evident in womenalternate day dosing can reduce the effect on lipoproteins in someCyclosporin (immunosuppressant)increases LDL levels, HT and glucose intoleranceUsually administered along side glucocorticoidsAffects lipid levels in transplant patientsHepatic microsomal enzyme inducersIncludes carbamazepine, phenytoin, phenobarbitone, rifampicin and griseofulvincan increase serum HDL levelssmall increase in LDL and VLDLoverall increases HDL to serum LDL ratioPatients treated for epilepsy tend to have a decreased incidence of IHD
6 Is the effect of thiazide diuretics on lipid levels of clinical sig.? Thiazides tend to the production of VLDL from the liverContains level TGsMay cause in plasma TGs in some Px’s NOT usually clinically sig.v. few Px marked TGs risk vascular problems or pancreatitisDiuretics used manag. of hyperT by ing BPAlso shown to prevent:Strokes, MI & CHF
7 Various types of thiazide diuretics used in high doses showed: Short term studies have shown that high dose diuretics (>50mg/day) may affect lipoprotein profilesVarious types of thiazide diuretics used in high doses showed: T.CH by ~ 4% sLDL ~10%Lesser effects on VLDLNo ∆ in HDLHigh doses thiazides NOT shown greater benefitDoses >25mg/day of hydrochlorothiazide or demonstrated rel. flat D-R curveThe likelihood of metabolic events such as CHO, e-, & lipid abnormalities may be less with lower doses aim min effect on lipid levels yet retain anti-hypoT effectFound that indapamide 2.5mg/day is equipotent to 50mg hydrochlorthiazide but has better lipid tolerability
8 Is it a sustained effect? High dose thiazide diuretics sustained effectLg scale clinical trial studies show NO effect on lipid levels after 3-5 years of useDuring 1st yr sCH levels may sig.However return back to or baseline after a yr of TxLong-term Tx w. thiazide diuretics modest elevation sCH level may occur during the 1st yr but subsides back to or baseline value after a year of therapy.Thiazide-induced ∆ seem to be D-R & may resolve w. discontinuation of Tx.
9 Proposed MOA Thiazide-Induced Effect on Lipid Levels The exact mechanism responsible for CH ∆ is uncertain.Many proposed mechanisms:Stim. of catecholamine release in response to vol. depletionCatecholamines stimulate hepatic CH synthesisHypokalemia proposed as a causeAddition of a K+ sparing diuretic to a thiazide regimen may limit the observed elevation in CHAn in serum glucose or insulin secretion has also been suggested as the aetiology of the TG elevationThiazide-induced reduction in insulin sensitivity may cause an associated in hepatic production of CHHowever, this observation may be more related to the reduction in serum K that may occur w. dosages of thiazides
10 HyperlipidaemiaDefined as an elevation in one or more of CH, cholesterol esters, phospholipids, or TG.Can result in premature coronary atherosclerosis, leading to manifestations of IHD.
11 Classification of Dyslipidemias May be 1° or 2°:1° forms - genetically determined & classified according to lipoprotein particles raised2° forms: - consequence of other conditions such as:DMAlcoholism,Nephrotic syndromeCRF
12 Frederickson/WHO classification of Hyperlipoproteinaemia 1° DyslipidemiasFrederickson/WHO classification of HyperlipoproteinaemiaTypeLipoprotein CHTGAtherosclerosisDrug TxIChylomicrons++++NENoneIIaLDL++HighHMG-CoA reductase inhibitors +/- resinsIIbLDL+VLDLFibrates, HMG-CoA reductase inhibitors, nicotinic acidIIIVLDLModerateFibratesIVFibrates (+/- fish oil)VNone (+/- fish oil)
13 Clinical dyslipidemia assessment Once 2° causes & other medications have been ruled out as a cause of dyslipidemia, the Px’s lipid profile guides therapy(Based on Frederickson’s classification)
14 Back to the Px…. What should we do? Mrs TZ hyperlipidemiaRecommend?StatinFish oilsNon pharmacological TxDiet fat intakeExerciseAvoid smoking & alcohol