PharmD 4L PATHOPHYSIOLOGY OF CARDIOVASCULAR DISORDERS

Prof Azuka C Oparah

BPharm, MPharm, MBA, MPH, PhD, FPCPharm, FPSN, FNAPharm

Department of Clinical Pharmacy & Pharmacy Practice

University of Benin
Email: [email protected]; Tel: +234 8023328341
 Hypertension
Learning Objectives

I. Define and classify arterial blood pressure based on JNC 7

II. Describe appropriate measurement of blood pressure
III. Explain hypertension, its etiologies and complications
 Introduction
High blood pressure is a major public health chronic
disease as well as cardiovascular risk factor in several
other cardiovascular conditions worldwide.

BP = TPR x CO (Resistance & Volume

components)
CO = HR x SV

Initiating factors ≠ Maintenance factors

Genetic & Vascular adaptation
environmental
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 Hypertension -Definition

Persistent elevation of arterial blood pressure

(diastolic and or systolic) equal to or above 140/90
mmHg (BP ≥ 140/90 mmHg) in an adult of 18 years or
above.

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 Hypertension - Etiology
• In 90 – 95% or the majority of the cases, the cause of
the high blood pressure is unknown. i.e. primary or
idiopathic hypertension. They have risk factors

• Some 5 – 10% or minority of the cases of

hypertension can be traced to an identifiable cause
i.e. Secondary hypertension

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 Classification of blood pressure for adults JNC 7

Blood Pressure Systolic BP Diastolic BP

Normal < 120 mmHg and < 80 mmHg

Pre-hypertension 120 – 139 mmHg or 80 – 89 mmHg
Stage 1 140 – 159 mmHg or 90 – 99 mmHg
Stage 2 ≥ 160 mmHg or ≥ 100 mmHg

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Hypertension: urgencies and emergencies (Hypertensive Crisis)

• Urgencies : severe elevations in BP (typically, 180/120) without

symptoms or evidence of acute end organ damage; oral agents,
over a time course of hours to days, ideally within 24 to 48
hours are indicated.

• Emergencies: severe elevations in BP that are associated with

acute injury to target organs such as the brain, heart, kidneys,
retina, and other vasculature. Examples include hypertensive
encephalopathy, intracerebral hemorrhage, acute MI, acute
coronary syndromes, acute left ventricular failure with
pulmonary edema, dissecting aortic aneurysm, and acute renal
failure. BP must be lowered immediately but cautiously by
parenteral therapy.

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 Risk Factors: Primary HTN

• Age (middle age or older persons)

• Hypertension
• Cigarette smoking
• Obesity (body mass index ≥ 30 kg/m2); central obesity
• Physical inactivity
• Dyslipidemia
• Diabetes mellitus
• Microalbuminuria or estimated GFR < 60 mL/min
• Family history of premature cardiovascular disease
(men under age 55 or women under age 65)
• Salt intake
• Stress

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 Identifiable causes of secondary hypertension

• Sleep apnea
• Drug-induced or related causes
• Chronic kidney disease
• Primary aldosteronism
• Renovascular disease
• Chronic steroid therapy and Cushing’s syndrome
• Pheochromocytoma
• Coarctation of the aorta
• Thyroid or parathyroid disease

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 Rx Drugs associated with secondary hypertension
• Corticosteroids
• Estrogens (usually oral contraceptives with high estrogenic
activity)
• Nonsteroidal anti-inflammatory drugs, a COX-2 inhibitors
• Phenylpropanolamine and analogues
• Cyclosporine and tacrolimus
• Erythropoetin
• Sibutramine
• Antidepressants (especially venlafaxine), bromocriptine,
buspirone,
• carbamazepine, clozapine, desfulrane, ketamine,
metoclopramide
• Clonidine (rebound hypertension)
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 Hard Drugs and Other Natural Products
• Cocaine
• Marihuana ”herbal ecstasy,” and other
phenylpropanolamine analogues
• Nicotine
• Anabolic steroids and withdrawal
• Narcotic withdrawal
• Methylphenidate, phencyclidine, ketamine, ergotamine
and other
• Ergot-containing herbal products, St. John’s wort

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 Food Substances
• Sodium
• Ethanol
• Licorice
• Tyramine-containing foods if taking a monoamine
oxidase inhibitor

Chemical Elements and Other Industrial Chemicals

• Lead, mercury, thallium and other heavy metals,
lithium

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 Signs and Symptoms
• Hypertension is asymptomatic

• Symptoms may be due severe elevation of BP or

organ damage

Some people report:

• Occipital headaches
• fatigue
• dizziness
• blurred vision
• facial flushing
• tinnitus.
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 Diagnosis
• Measurement of arterial blood pressure using a validated
apparatus
• Appropriate cuff size
• No prior intake of coffee or caffeine
• No tight dressing, empty bladder if full
• Patient should rest for at least 5 minutes
• 2 to 3 measurements about the same time on different days
• Patient seated, feet on flat surface, with arm at the level of
heart
• Take average of 2 to 3 close readings

• When there is persistent elevation, assess for organ

damage: eye, kidney, heart.

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 Target organ damage in hypertension

• Heart
– Left ventricular hypertrophy
– Angina or prior myocardial infarction
– Prior coronary revascularization
– Heart failure
• Brain
– Stroke (Cerebrovascular accident, CVA: hemorrhagic &
ischemic )
– Transient ischemic attack

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 Target organ damage in hypertension...
• Kidney
– Chronic kidney disease
– Chronic renal failure
• Eye
– Retinopathy
– Blindness due to damage to optic disk

• Peripheral arterial disease

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 Congestive Cardiac Failure

Learning Objectives

I. Illustrate the cardiovascular disease continuum

II. Explain cardiac failure and the compensatory
mechanisms
III. Describe the mechanism of edema formation in
cardiac failure

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 Cardiovascular Disease Continuum

• The CVD continuum is a sequence of CV events, which begins

from a cluster of CV risk factors consisting of DM, dyslipidemia,
HT, smoking and visceral obesity.

• And if these factors are not intervened with early, they will,
inexorably, progress to atherosclerosis, CAD, MI, LVH, LV
dilatation leading to LV diastolic or systolic dysfunction and
eventually end stage HF and death

• The pathophysiological processes include oxidative stress,

endothelial dysfunction, inflammation, and vascular remodeling
in the initiation and continuation of atherosclerotic disease.
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Figure 1. The cardiovascular disease continuum.
.
Dzau et al. Circulation. 2006;114:2850-2870 19
 What is Cardiac Failure?
• The inability of the heart to pump sufficient blood to meet
tissue metabolic requirements. Heart failure may be acute
(high output) or chronic (low) output.

• It is not to be confused with "cessation of heartbeat", asystole,

or with cardiac arrest, which is the cessation of normal cardiac
function with subsequent hemodynamic collapse leading to
death.

• HF can be caused by an abnormality in cardiac structure,

function, rhythm, or conduction.
• Ventricular dysfunction (e.g. due to HT & MI) most common
underlying problem leading to low cardiac output, despite the
demand 20
 Compensatory Mechanisms in Cardiac Failure
• Increase in adrenergic neurone activity, with reduced vagal
activity to the heart – positive ionotropic and chronotropic
effects

• Left ventricular hypertrophy with or without chamber

dilatation- cardiomegaly

• Frank Starling Mechanism – overlapping of contractile filaments

(length/tension or force/ velocity)
• Activation of the Renin- Angiotensin- Aldosterone System
(RAAS) leading to oedema formation.

• NB: Cardiac failure is functionally failure of the compensatory

mechanisms

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 Cardiac Failure

• Left ventricular failure

• Right ventricular failure
• Biventricular failure

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 Clinical Manifestations
• The left ventricle pumps blood from the lungs to the
organs, left ventricular failure leads to congestion in the
lungs:

• Dyspnea (difficulty in breathing)

• Orthopnea
• Paroxysmal nocturnal dyspnea – cardiac asthma
• S3 gallop rhythm etc

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 Clinical Manifestations
• The right ventricle pumps blood from the tissues to the
lungs. Hence, failure of the right ventricle leads to
congestion of peripheral tissues.

• Peripheral edema or anasarca

• Nocturia
• Ascites
• Hepatomegaly
• Hepatojugular reflux

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 Physical examination of the Heart
• Precordium – Increase in precordial activity

• Apex beat – Shift in point of maximal impulse (PMI)

• Abnormal sound – more than 2 as in murmur or stenosis

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 Myocardial Infarction
Learning Objectives
I. Distinguish between angina and myocardial infarction
(MI)
II. Identify the signs and symptoms of MI
III. Explain the pathophysiological principles in MI
IV. Outline common diagnostic tests for MI

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 Definitions
• Cholesterol: An essential fat-like substance used in the
manufacture of vitamin D and hormones; found predominantly in
animal fat, egg yolks and milk products.

• Atherosclerosis: Accumulation of fatty deposits on the wall of

vessel leading to narrowing of the diameter of the wall

• Arteriosclerosis: Hardening or thickening of the blood vessel

wall.

• Angina: Pain in the chest usually due to inadequate oxygen

supply to the heart muscle.

• Myocardial infarction: Irreversible heart muscle damage due to

prolonged deprivation of oxygen because of inadequate blood
flow.
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 Definitions
within a blood
• Thrombus: vessel
A clot or cavity of
formed
the heart which remains attached to the site of forma

• Embolus: Part of clot which breaks away and circulates

through the blood stream.

• Myocardial infarction (MI, ‘heart attack’, ‘coronary

thrombosis’) occurs when a coronary vessel becomes
occluded for more than about 6 h, whether or not the
occlusion is subsequently relieved. Unlike for angina,
exertion is not a trigger for MI, and although MI is
frequently associated with current stress or general ‘life
events’. Angina and MI stand at either end of a spectrum of
ischemic states referred to as acute coronary syndrome
(ACS).
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 Myocardial Infarction

• Myocardial infarction (MI, ‘heart attack’, ‘coronary

thrombosis’) is an ischemic necrosis of the myocardium,
caused by occlusion of coronary artery and prolonged
myocardial ischemia. MI is an extreme consequence of
acute coronary syndrome.

• Unlike for angina, exertion is not a trigger for MI, and

although MI is frequently associated with current stress or
general ‘life events’. Angina and MI stand at either end of a
spectrum of ischemic states referred to as acute coronary
syndrome (ACS).

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 Angina vs. Myocardial Infarction
Angina Myocardial infarction

Caused by atherosclerosis Caused by atherosclerosis

Triggered by exertion Triggers often unknown
Pain: severe, crushing, Pain: severe, crushing,
retrosternal, possibly radiating retrosternal, possibly radiating

Pain reversed on resting few minutes Pain persistent

Pain relieved by Glyceryl trinitrate Pain not relieved by GTN
Increased Oxygen demand Decreased Oxygen supply
Partial obstruction Complete occlusion
Myocardial hypoxia Myocardial anoxia
Reversible Irreversible

Pathology & Therapeutics for Pharmacists

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 Pathophysiology of Myocardial Infarction
• Most patients who sustain an MI have coronary
atherosclerosis.
• The thrombus formation occurs most often at the site of an
atherosclerotic lesion, thus obstructing blood flow to the
myocardial tissues.
• Plaque rupture is believed to be the triggering mechanism
for the development of the thrombus in most patients with
an MI.
• When the plaques rupture, a thrombus is formed at the site
that can occlude blood flow, thus resulting in an MI.
• Irreversible damage to the myocardium can begin as early
as 20 to 40 minutes after interruption of blood flow.
• The dynamic process of infarction may not be completed,
however, for several hours.
• Necrosis of tissue appears to occur in a sequential fashion.
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 Pathophysiology of Myocardial Infarction
• a substantial amount of myocardial tissue can be salvaged if
flow is restored within 6 hours after the onset of coronary
occlusion.
• The cellular changes associated with an MI can be followed
by:
1. the development of infarct extension (new myocardial
necrosis),
2. infarct expansion (a disproportionate thinning and dilation
of the infarct zone), or
3. Ventricular remodeling (a disproportionate thinning and
dilation of the ventricle).

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 Size of the Infarction
• Several factors determine the size of the resulting MI.

• These factors include the extent, severity, and duration of the

ischemic episode; the size of the vessel; the amount of
collateral circulation; the status of the intrinsic fibrinolytic
system; vascular tone; and the metabolic demands of the
myocardium at the time of the event.

• MIs most often result in damage to the left ventricle, leading

to an alteration in left ventricular function.
• Infarctions can also occur in the right ventricle or in both
ventricles.

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 Size of the Infarction

• The term transmural infarction is used to imply an infarction

process that has resulted in necrosis of the tissue in all the
layers of the myocardium.
• Because the heart functions as a squeezing pump, systolic and
diastolic efforts can be significantly altered when a segment
of the heart muscle is necrotic and nonfunctional.
• If the area of the transmural infarction is small, the necrotic
wall may be dyskinetic, a term meaning “difficulty in moving.”
• If the damage to the myocardial tissue is more extensive, the
myocardial muscle may become akinetic, meaning “without
motion.”

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 Clinical Manifestations
• Pain is the cardinal symptom of an MI
• Fever within the 1st 24 hr and may last up to a week
• Anxiety and fear of impending death
• Nausea and vomiting
• Breathlessness
• Collapse/syncope
Physical signs
• Signs of sympathetic activation: pallor, sweating, tachycardia
• Signs of vagal activation: nausea, vomiting, bradycardia
• Signs of impaired myocardial function: hypotension, oligurea, cold
peripheries
• Signs of complications: e.g. Arrhythmias, congestive heart failure,
mitral regurgitation, pericarditis, cardiogenic shock, pulmonary
embolism

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 Diagnostic Tests
The Electrocardiogram
• An ECG can be used to detect patterns of ischemia, injury, and
infarction
Ischemia
• On the ECG, myocardial ischemia results in T-wave inversion
or ST segment depression in the leads facing the ischemic
area.
• The inverted T wave representative of ischemia is
symmetrical, relatively narrow, and somewhat pointed.

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Laboratory Tests
• Creatine Kinase
• CK-MB appears in the serum in 6 to 12 hours, peaks between
12 and 28 hours, and returns to normal levels in about 72 to
96 hours.
• Serial samplings are performed every 4 to 6 hours for the first
24 to 48 hours after the onset of symptoms
• Creatine Kinase Isoforms: CK-MB1 is the isoform found in the
plasma, and CK-MB2 is found in the tissues.
• Myoglobin: Myoglobin is an oxygen-binding protein found in
skeletal and cardiac muscle. Myoglobin’s release from
ischemic muscle occurs earlier than the release of CK.
• The myoglobin level can elevate within 1 to 2 hours of acute
MI and peaks within 3 to 15 hours; not specific for MI
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Laboratory Tests
• Troponin. (troponin T and troponin I):
• Troponin I levels rise in about 3 hours, peak at 14 to 18 hours,
and remain elevated for 5 to 7 days.
• Troponin T levels rise in 3 to 5 hours and remain elevated for
10 to 14 days

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 DYSLIPIDEMIA
Learning Objectives

I. List types of blood lipid and their normal values

II. Outline causes of secondary dyslipidemia

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 DYSLIPIDEMIA
• Dyslipidemia is defined as elevation of plasma cholesterol,
triglycerides (TGs), or both or a low density lipoprotein level.

• Dyslipidemia is sometimes called hyperlipidemia (high

cholesterol)
• Dyslipidemia has no obvious symptoms (asymptomatic)
• Dyslipidemia is a known factor of cardiovascular disease (CVD)

• The underlying causes of dyslipidemia are both genetic

(primary) and unhealthy lifestyle or disease.

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 Two Types of Lipids

LIPIDS IN BLOOD

TOTAL CHOLESTEROL TRIGLYCERIDES (TG)

GOOD CHOLESTEROL BAD CHOLESTEROL

HDL 1 and HDL 2 LDL, VLDL (TG), Lp(a)

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 Normal Lipid Profile

• Total Cholesterol < 200

• TG ‘Ugly’ Lipid < 150
• ‘Bad’ Cholesterols LDL < 100
• HDL ‘Good’ cholesterol > 50
• VLDL is Ugly TG ÷ 5 < 30
• Lp(a) ‘Deadly’ cholesterol < 20

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 Hyperlipidemias

Primary 5%
Familial & genetic

Secondary 95%

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 Secondary dyslipidemia

– Hypothyroidism
Drugs & Dyslipidemia
– Obstructive liver disease
• Corticosteroids
– Nephrotic syndrome • Androgenic steroids
– Renal failure • Progestogens
– Uncontrolled diabetes • Thiazides
– Obesity • -adrenoceptor blockers
• Retenoic acid derivatives
– Diet & sedentary lifestyle
• Oral estrogens
– Tobacco or alcohol use
– Medications  consider
stopping
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 GROUP DISCUSSION

1. How is hypertension a common risk factor to

cardiovascular disorders?

2. What is your view on the ongoing views that

there is no bad cholesterol?

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