Ischaemic Heart Disease

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 BP readings
• 180/95mmHg
• 185/90mmHg
• 185/95mmHg
• Recent clinical chemistry data

TC 7.6mmol/L lt5.5
TG 3.3mmol/L lt2.0
HDL 0.7mmol/L 0.9-2.0
4
Estimating LDL

• Using Friedewald equation
• LDL TC HDL TG mmol/L
• 2.19
• 7.6 0.7 3.3
• 2.19
• Mrs TZ LDL 5.4 mmol/L
• LDL gt 5 mmol/L excessive even in the absence of
  risk factors
• ? Foundation of Oz Guidelines
• LDL gt 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

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 Pxs
• ? 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

• Short term studies have shown that high dose
  diuretics (gt50mg/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 gt25mg/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

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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.

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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

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1 Dyslipidemias
Frederickson/WHO classification of Hyperlipoproteinaemia
Type Lipoprotein ? CH TG Atherosclerosis Drug Tx
I Chylomicrons NE None
IIa LDL NE High HMG-CoA reductase inhibitors /- resins
IIb LDLVLDL High Fibrates, HMG-CoA reductase inhibitors, nicotinic acid
III VLDL Moderate Fibrates
IV VLDL Moderate Fibrates (/- fish oil)
V Chylomicrons NE None (/- fish oil)
13
Clinical dyslipidemia assessment

• Once 2 causes other medications have been
  ruled out as a cause of dyslipidemia, the Pxs
  lipid profile guides therapy
• (Based on Fredericksons classification)

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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