1. Ischaemic Heart Disease
Case E

2. The History
Mrs 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 D
Plavix (Clopidogrel) 75mg 1 D

3. Recent clinical chemistry data:
Recent BP readings:
180/95mmHg
185/90mmHg
185/95mmHg
Recent clinical chemistry data: TC
7.6mmol/L
<5.5 TG
3.3mmol/L
<2.0
HDL
0.7mmol/L

4. Estimating LDL Using Friedewald equation: LDL = TC – HDL – TG mmol/L
2.19
= 7.6 – 0.7 – 3.3
Mrs TZ LDL = 5.4 mmol/L
LDL > 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 medications
Thiazide & loop diuretics
 VLDL & LDLs
 blockers
especially Propanolol –  HDL &  total CH/HDL CH ratio
Others include:
Hepatic microsomal enzyme inducers
OCs
GCs
A lg # of meds can adversely affect serum lipid & lipoprotein [ ]s:
Oral contraceptives
Oestrogen causes a slight increase in hepatic production of VLDL and HDL, reduces serum LDL levels in post menopausal women
Progestogen increases LDL and reduces serum HDL and VLDL
Corticosteroids
Glucocorticoids shown to increase serum CH and TGs by elevating LDL, and VLDL to a lesser extent
more evident in women
alternate day dosing can reduce the effect on lipoproteins in some
Cyclosporin (immunosuppressant)
increases LDL levels, HT and glucose intolerance
Usually administered along side glucocorticoids
Affects lipid levels in transplant patients
Hepatic microsomal enzyme inducers
Includes carbamazepine, phenytoin, phenobarbitone, rifampicin and griseofulvin
can increase serum HDL levels
small increase in LDL and VLDL
overall increases HDL to serum LDL ratio
Patients 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 liver
Contains  level TGs
May cause  in plasma TGs in some Px’s
 NOT usually clinically sig.
v. few Px marked  TGs  risk vascular problems or pancreatitis
Diuretics used manag. of hyperT by ing BP
Also 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 profiles
Various types of thiazide diuretics used in high doses showed:
 T.CH by ~ 4%
 sLDL ~10%
Lesser effects on VLDL
No ∆ in HDL
High doses thiazides NOT shown greater benefit
Doses >25mg/day of hydrochlorothiazide or  demonstrated rel. flat D-R curve
The 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 effect
Found 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 effect
Lg scale clinical trial studies show NO effect on lipid levels after 3-5 years of use
During 1st yr sCH levels may  sig.
However return back to or  baseline after a yr of Tx
Long-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. depletion
Catecholamines stimulate hepatic CH synthesis
Hypokalemia proposed as a cause
Addition of a K+ sparing diuretic to a thiazide regimen may limit the observed elevation in CH
An  in serum glucose or insulin secretion has also been suggested as the aetiology of the TG elevation
Thiazide-induced reduction in insulin sensitivity may cause an associated  in hepatic production of CH
However, this observation may be more related to the reduction in serum K that may occur w.  dosages of thiazides

10. Hyperlipidaemia
Defined 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 raised
2° forms: - consequence of other conditions such as: DM
Alcoholism,
Nephrotic syndrome
CRF

12. Frederickson/WHO classification of Hyperlipoproteinaemia
1° Dyslipidemias
Frederickson/WHO classification of Hyperlipoproteinaemia
Type
Lipoprotein  CH TG
Atherosclerosis
Drug Tx I
Chylomicrons +
+++ NE
None
IIa
LDL ++
High
HMG-CoA reductase inhibitors +/- resins
IIb
LDL+VLDL
Fibrates, HMG-CoA reductase inhibitors, nicotinic acid
III
VLDL
Moderate
Fibrates IV
Fibrates (+/- fish oil) V
None (+/- 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 hyperlipidemia
Recommend?
Statin
Fish oils
Non pharmacological Tx
Diet   fat intake
Exercise
Avoid smoking & alcohol