Lipids And Cardio Part 3

IHD causes, non lipid: Homocysteine – oxidizes LDL 10% risk Treatment – diet. Lipoprotein a [Lp(a)] 15-20% of population Increases risk Treatment is ?

Lipoprotein a Healthy Caucasians 20-500 g/L Afro-Americans 50-720 g/L Levels above 300 g/L are risk if under 55 years of age. 95% of molecule same as plasminogen. Lp(a) is 15% of total cholesterol so can have normal serum cholesterol. Lack of standards, reference methods means some chaos in interpretation.

Gut enzyme that transports out sterols: Deficient then MI at age 6 – 8 years. Plant sterols absorbed with cholesterol but Cannot get the plant sterols out. Atherosclerotic lesions develop from the plant sterols Source: Hegele at Western 2004.

Link between infection and heart disease: Chlamydia Coxsackie virus TWAR (Taiwanese acute reactin) and others Could heart diseases be an autoimmune disease? Sudden unexplained death in athletes Josef Penninger PMH.

80 year old man, chest pain and hypotension: Serum Cholesterol, HDL cholesterol, LDL cholesterol and triglyceride are all normal. Serum homocysteine increased Serum folate decreased Serum vitamin B12 normal Serum vitamin B6 decreased Cause – micronutrients deficiency?

The failing heart: Ischaemic heart disease Acute coronary syndrome Myocardial infarction Re infarction Death.

Evolution of markers for ischaemic heart disease: ECG Serum Cholesterol Serum Triglyceride (fasting) Serum HDL and LDL cholesterol, oxidized LDL Serum Homocysteine Serum Lp(a) Serum C-reactive protein. Serum troponin. (hair loss, premature graying.)

Acute coronary insufficiency: Pre infarct state Serum troponins In Europe high sensitivity serum C-reactive protein. Higher the level the less likely is long term survival.

Myocardial infarction: Chest pain: angina pectoris ECG abnormal Changes in plasma enzymes/proteins Causes: atheroma, clotting. Blockage of blood flow to part of heart –ischaemic heart disease. Preceded by coronary insufficiency syndrome.

Heart and Stroke Foundation suggestions: 25% of myocardial infarcts MI have no chest pain Paleness Anxiety, fear, denial Sweating Shortness of breath Indigestion Tightness or chest pain Overall weakness Nausea PASS IT ON

Coronary artery disease

49 year old man, chest pain during an argument. Could it be MI? Emergency Room, ECG done Plasma CK/troponin I or T at time in ER, then 6 and 12 hours after estimated time of infarct Plasma CKMB, (CK2)/troponin Recently: serum or plasma myoglobin, [glycogen phosphorylase BB].

troponin

Treatment of MI/Acute coronary syndrome (ACS): Aspirin – most patients self medicate before ER. Heparin Tissue plasminogen activator Platelet blockers – glycoprotein IIb/IIIa ($800-1,200)

Management post MI: s-CK or s-troponin is followed over time. sCK is normal in a few days but s-troponin is up for weeks. Check for reperfusion Check for reinfarction Try to get life style changes in patient.

Markers for myocardial infarct

Critique of cardiac markers

Cardiac markers over time

Cardiac bypass surgery: Heart stopped and by pass vein grafted round obstruction Brain is oxygenated but the rest of the body is not (<4 hours) Laboratory supplies blood gases and electrolytes with 2 minute turn around time in laboratory. “healthy” patients <1% die “high risk” 25% die. Need practice to do well – institute for clinical evaluative studies ICES.

Cardiac by pass surgery: Most common surgery in North America. Up to 6/day at Sunnybrook. Quality of life improved. Death rate unchanged. Some brain damage is common.

Congestive heart failure is a big problems

Congestive heart failure: Increased venous pressure, breathless, cough, wheeze, oedema, hepatomegaly, raised jugular venous pressure JVP, dizziness, syncope, fatigue, low blood pressure, cardiomegaly. Liver function tests, Natriuretic peptides A, B and C type, Complete blood count CBC, Thyroid function tests.

Cardiac changes leading to CHF Ventricular Remodeling in post-AMI and in Heart Failure

NEJM (2003) 348:2007-18.

Natriuretic peptide Pharmacologic Actions of BNP Hemodynamic (balanced vasodilation)  venous tone  arterial tone R I SS D S M S K G R L G H G F R C S S CK V L R G S PKM V Q GS

Neurohumoral  renin/aldosterone release Renal diuresis  natriuresis 

Natriuretic peptide Vasodilation Promotion of natriuresis and diuresis Inhibition of the sympathetic nervous system Inhibition of several hormone systems such as the renin angiotensin aldosterone system Effects on cardiovascular system

bnp

Production of BNP

Characteristics of the BNPs BNP Hormonally active 22 minute half life Clearance through natriuretic peptide receptor C and enzymatic degradation by neutral endopeptidase

NT-proBNP Hormonally inactive 1-2 hours half life Clearance through the reticuloendothelial system and renal clearance.

Clinical use of BNP and NTproBNP Diagnosis of heart failure (May be hard to tell from COPD – SOB patients) Prognostic marker for subsequent cardiac events Treatment monitoring for management of heart failure patients.

BNP is not specific for CHF Increased post MI Multiple trauma Abdominal or thoracic surgery Subarachnoid hemorrhage, some brain tumours Diabetes Renal failure Pulmonary embolism, lung cancer Ventricular hypertrophy and cardiomegaly

CHF BNP algorithm