Cardiovascular Disease

Hypertension
Dr.Ahsan Ayub
Assocciate Professor of Medicine
Islam Medical & Dental College
Introduction
Elevated blood pressure: HYPERTENSION
Optimum BP w.r.t cardiovascular risk:
 Systolic BP <120 mmHg
 Diastolic BP <80 mmHg

Isolated Systolic Hypertension

 SBP >140; DBP <90
Presence/ absence of ‘end-organ’ disease
 Brain, eye, heart, kidney
 Classification of BP (>18yr)
Category Systolic Diastolic
Normal <130 <85
High Normal 130-139 85-89
Hypertension
Stage 1 (mild) 140-159 90-99
Stage 2 (moderate) 160-179 100-109
Stage 3 (severe) 180-209 110-119
Stage 4 (very severe) >210 >120
When systolic and diastolic fall in different categories, the higher category is selected
Epidemiology
Proportion of people with HTN  with age

Blacks > whites

Causes
Primary (essential) HTN – 90%
Renal HTN – 5%
 Renal parenchymal 3%
 Renovascular HTN <2%
Endocrine – 4-5%
 Oral contraceptives 4%
 Primary aldosteronism 0.5%
 Pheochromocytoma 0.2%
 Cushing’s syndrome 0.2%
Coarctation of aorta – 0.2%
Primary Hypertension
No cause established
95% of cases of hypertension
10-15% of all whites
20-30% of all blacks
Onset ages 25 to 55yr
 Uncommon <20yr
Mutifactorial
 Genetic
  salt intake
  sympathetic nervous system hyperactivity
 …..
Clinical Features - Symptoms
Asymptomatic
Sub-occipital pulsating headache
 Early morning; subsiding during the day
Accelerated HTN: encephalopathy
 Somnolence; confusion; visual disturbance; nausea;
vomiting
Exertional dyspnea; PND
 Early – diastolic dysfunction
 Later – systolic dysfunction
Chronic HTN
 Symptoms related to end organ damage
Clinical Features - Signs
Elevated blood pressure
Keith-Wagner retinal changes
Loud A2; early systolic murmur
LV heave; S4 common (LV
compliance)
Radioradial delay – aortic dissection
Radiofemoral delay – coarctation
How to measure BP
Well calibrated sphygmomanometer
Proper cuff size (80% of circumference)
Resting comfortably for 5 minutes
Supported back or supine; relaxed arm
At least 30min after smoking or caffeine
Check both arms; arm with pressure used
subsequently
Apparatus, cuff and heart at same level
Diagnose after three elevated readings at
various times
 Unless severe elevation or symptomatic
Transient elevation of BP
 Anxiety
 Excitement
White coat hypertension
 Ambulatory 24hr monitoring
 BP but no end –organ damage (LVH)
 Treatment-related hypotensive symptoms
 HTN resistant to treatment
Investigations
Labs: Recommended tests include
 Hemoglobin
 Urinalysis (hematuria, proteinuria, casts)
 BUN, creatinine (renal function tests)
 Serum potassium ( K in hyper-aldosteronism)
 Fasting blood sugar ( glucose in diabetes &
pheochromocytoma)
 Plasma lipids (risk factor for atherosclerosis)
 Serum uric acid ( = relative contraindication to
diuretics)
CXR:
 Not recommended in routine HTN
 No additional information
ECG: very specific;  sensitivity
 LV hypertrophy
 Strain pattern – poor prognosis
Echo:
 LV hypertrophy
 Evaluate HTN with cardiac disease; no routine use
Other studies: for secondary HTN
 Additional blood/ urine tests
 Renal USG (polycystic kidney, obstructive uropathy)
 Renograms, renal arteriography, CT, MRI
Secondary Hypertension
5% of all patients with HTN
HTN at an early age with no family
history
HTN diagnosis >50yr
Well-controlled HTN which becomes
refarctory to treatment
Numerous causes
Causes
Estrogen use
Renal disease
Renal vascular hypertension
Primary hyperaldosteronism
Cushing’s syndrome
Pheochromocytoma
Coarctation of aorta
Others: pregnancy, Ca, acromegaly, /
thyroid, medicines (cyclosporine, NSAID)
Estrogen use
5% females on chronic OCP have BP >140/90
(twice expected prevalance)
 Females >35yr; OCP use >5yr, obese
Volume expansion from  renin-angiotensin–
aldosterone system
 hepatic synthesis of renin
Reversible by discontinuing OCP
  over several weeks
Less common with low dose estrogen tabs
No evidence of HTN in postmenopausal OCP
Renal causes
Most common cause of secondary HTN
Any disease of renal parenchyma
 Glomerular disease
 Tubular interstitial disease
 Polycystic kidneys
 Diabetic nephropathy

 Renin-angiotensin-aldosterone system
HTN  renal insufficiency – target BP
<139/85
Renal Vascular HTN
Renal artery stenosis (RAS)
 Fibromuscular hyperplasia (females <50yr)
 Atherosclerotic stenoses of proximal renal
arteries
 Renin causes  renal blood flow &
perfusion pressure
25% bilateral
75% single branch stenosis
Suspected if:
 HTN in patients <20yr or >50yr
 Epigastric/ renal bruits

 Atherosclerotic disease of aorta/ peripheral

artery (15-25% symptomatic lower limb PVD
have RAS)
 Abrupt  of renal function after ACE-inhibiter
administration
 HTN which is difficult to control
Investigation:
 High suspicion- Renal arteriography
 Low-Mod suspicion- Renal captopril test
(radioisotope renography)
Treatment:
 Young patients; good risk pts (any age)
-percutaneous transluminal angioplasty
with stent
 Older patients- medical management
 ACE-I contraindicated in bilateral stenosis
Primary Aldosteronism
0.5% of hypertensives
 Aldosterone
Causes
 Adrenal adenoma
 Bilateral adrenal hyperplasia
Suspected when a patient with HTN has:
  S/K; U/K loss(>40 on spot specimen); plasma
renin; S/Na >140
 aldosterone in blood & urine
Investigation: CT; MRI
Others
Cushing’s syndrome:
  glucocorticoids
 HTN as initial presentation is less common

Pheochromocytoma:
 <0.1% of HTN
 Episodic HTN; sustained in some
 Orthostatic falls in BP; converse of
essential HTN
 Glucose intolerance
Complications
Complications caused by
  pressure on vasculature and heart
 Atherosclerosis that accompanies and is  with long
standing HTN
Risk of complications doubles for every 6mmHg  in
diastolic BP
Patients >50yr, SBP better predictor of complications
 SBP 140-159 associated with 42%  in stroke; 56%  in
cardiovascular death
Untreated HTN: rapid end-organ damage
Complications
Brain:
 TIA/ stroke
Eyes:
 Hemorrhages, exudates +/- papilledema
Heart and aorta:
 Evidence of CAD
 LVH or strain pattern on ECG, Echo
 LV dysfunction, heart failure
 Aortic dissection
Kidneys:
 Serum creatinine >1.5 mg/dl
 Microalbuminuria; proteinuria (=>1+)
Mortality rates
 Stroke & CHD  by >60%
 ESRD & heart failure continues to rise
Recommendations for follow-up
Initial Blood Pressure Recommended Follow-
Screening up
Systolic Diastolic
<130 <85 Recheck in 2 yr
130-139 85-89 Recheck in 1 yr
140-159 90-99 Confirm within 2 months
160-179 100-109 Evaluate within 1 month
180-209 110-119 Evaluate within 1 week
>210 >120 Evaluate immediately
Treatment
Objective of treatment:
 Prevent morbidity & mortality related to high blood
pressure
Drug Rx of stage II & III HTN  incidence of:
 Stroke by 30-50%
 CHF by 40-50%
 Fatal/ non-fatal MI by 10-15%
 Progression to accelerated HTN syndromes
Treatment options:
 General Measures
 Medications
When to initiate drug therapy
Consider two factors before deciding
whether medications should be started:
Assess overall CV risk
 Major risk factors
 End-organ disease/clinical CV disease

Level of BP
Cardiovascular Risk Stratification
Major risk factors:
 Smoking
 Dyslipidemia
 Diabetes mellitus
 Age >60yr
 Sex (men & postmenopausal women)
 Family h/o CAD (male <55yr; female <65yr)

End-organ damage:
 Brain, heart, kidneys, eyes, PVD
 Risk Stratification & Treatment
Risk Group B Risk Group C
Risk Group A
Blood Pressure At least 1 RF EOD/CVD and/or
Stages No Risk Factors; diabetes; +/-
(not diabetes);
No EOD/CVD other RF
No EOD/ CVD
High Normal Lifestyle Lifestyle Drug therapy
(130-139/ 85-89) modification modification
Stage 1 Lifestyle Lifestyle Drug therapy
(140-159/ 80-99) modification modification
(up to 12 mo) (up to 6 mo)
Stage 2 Drug therapy Drug therapy Drug therapy
(>160/ >100)
General Measures
Lifestyle modifications
 Weight reduction
 Regular physical activity (aerobic; 30min 3 to 4 times
per week)
 Reduce salt intake (<2.8g Na, <6g of NaCl per day)
 Adequate potassium (90 mmol/d), Ca, Mg intake
 Smoking cessation
 Diet ( saturated fat & cholesterol;  fruits)
 Moderation of alcohol intake (<1oz ethanol/ day)
Medications
SBP >160; DBP >90 after repeated measurements
– Medications
 Goal <140/90
High risk groups: Treated aggressively
 Diabetics
 Nephropathy
 Heart failure; CAD
High risk treated even though BP in high normal
range
Choice of 1st line therapy depends on co-morbidities
 Indication Drug
Diabetes (1 and 2 with proteinuria) ACE inhibitors
Diabetes (type 2) Low-dose diuretics
Heart Failure ACE inhibitors; diuretics; BB
Post-myocardial infarction BB (non ISA);ACE inhibitors (EF)
Angina BB; CCB
Isolated systolic hypertension (old) Diuretics (preferred); CCB
Preoperative hypertension BB
Atrial tachycardia/ fibrillation BB; CCB (non-dihydrpyridine)
Dyslipidemia Alpha blockers
Hyperthyroidism BB
Migraine BB(noncardioselective); CCB
Prostatism (BPH) Alpha blockers
Osteoporosis Thiazides
Renal insuff. (caution: RAS; Cr >3) ACE inhibitors
 Indication Unfavourable Drugs
Diabetes (1 and 2) BB; high-dose diuretics
Depression BB;central alpha agonists
Bronchospastic disease BB
Heart Failure CCB (except amlodipine)
Post-myocardial infarction CCB
Peripheral vascular disease BB
Dyslipidemia BB (non-ISA); diuretics (high dose)
Gout Diuretics
Liver disease Labetalol; methyldopa
Pregnancy ACE-inhibitors; ARB
Renal insufficiency Potassium-sparing agents
Renovascular disease ACE-inhibitors; ARB
ACE Inhibitors
Captopril; Enalapril; Ramipril; Lisinopril
Mode of Action
 Inhibit renin-angiotensin-aldosterone system
 Inhibit bradykinin degradation
 Stimulate vasodilating prostaglandin synthesis
 Reduce sympathetic nervous system activity
Mild to moderate hypertension
More effective in younger whites
Less effective in blacks, elderly and ISH
Combination of ACEI with diuretic or CCB very potent
Agent of choice in diabetes (1&2) with proteinuria
or renal dysfunction
ACEI (ramipril) CV death, non-fatal MI, non-fatal
stroke and new onset HF
Agent of choice(with diuretics) in patients with HF
or asymptomatic patients with EF
Side-effects:
 First dose hypotension
 Severe hypotension in bilateral RAS
 Chronic dry cough
 Hyperkalemia
 Dizziness
 Rash
 Angioedema
Angiotensin Receptor Blockers
Losartan; Valsartan; Candesartan
Anti-hypertensive effect
 ACEI = ARB (newer generation)
Do not cause cough; skin rashes
Uncertain efficacy in HF, asymptomatic low EF,
diabetic nephropathy
Side-effects:
 Hypotension renal failure in RAS
 Angioedema (rare)
Reserved for patients who cannot tolerate ACEI due to
cough
Alpha blockers
Prazosin; Terazosin; Doxazosin
Mechanism of action:
 Relax post-synaptic alpha receptors & smooth muscle
Side-effects:
 Marked (first dose) hypotension; syncope
 Palpitations; headache; nervousness
No adverse effect on serum lipids
 HDL; total cholesterol
Initial agents only in men with prostatism
Incidence of HF & stroke  when compared to diuretics
Beta blockers
Propranolol; Metoprolol; Atenolol; Labetalol
Mechanism of action:
 Decrease heart rate and Cardiac output
  Renin release
Effective in young white people ( renin)
1st choice in CAD, stable CHF, migraine, anxiety
Pharmacologic properties:
 Cardioselectivity;B1 (B2 bronchi, vasculature)
 Intrinsic sympathetic activity (ISA)
 Lipid solubility
 Combined alpha- & beta blockers
Side-effects:
 Bronchospasm (asthmatics, COPD)
 Depressed SA and AV nodal function
 Worsens LV failure (improves stable CHF)
 Nasal congestion
 Raynaud’s phenomenon
 CNS symptoms- nightmares; excitement; depression;
confusion
 Fatigue; lethargy; impotence
 All BB TG; cardioselective BB HDL; not in ISA
Caution:
 Relative contraindication in DM-I: mask hypoglycemic
symptoms and prolong them ( gluconeogenesis)
 Caution in PVD with rest pain
Calcium channel blockers
Nifedipine; Amlodopine; Verapamil; Diltiazem
Peripheral vasodialtion (>dihydropyridines)
All demographic groups and grades of HTN
Combination of CCB and diuretics is less additive
than with BB or ACEI
Caution with concomitant use of verapamil or
diltiazem with BB  HF, AV blocks
Avoid short acting CCB in patients with LVH
Side-effects:
 HA; flushing; peripheral edema; constipation; HR
 Heart failure (less with amlodipine)
Centrally acting drugs
Methyldopa; Clonidine; Guanfecine
Mechanism of action:
 Central sympatholytic action
 Stimulate alpha-adrenergic receptors in CNS   efferent
sympathetic outflow
2nd or 3rd line because of drug intolerance
Side-effects:
 Fatige; dry mouth; postural hypotension; impotence
 Rebound hypertension when discontinued
 Hepatitis; hemolytic anemia (methyldopa)
Methyldopa useful in pregnancy
Diuretics
Hydrochlorothiazide; Metolazone; Amiloride;
Spironolactone; Furosemide; Bumetanide
Most extensively studied antihypertensive; most
consistently effective in clinical trials
Mechanism of action:
  plasma volume (tubular reabsorption of Na   Na
and water loss)
 Chronic therapy-  peripheral vascular resistance
May be dosed every other day with equal efficacy
More potent in blacks; older patients; obese; 
volume but  renin levels
More effective smokers > non-smokers
 osteoporosis
 Thazides retain calcium
 Loop diuretics lose calcium
Most effective agent in ISH
Useful in combination therapy
Side-effects:
 Metabolic- glucose, LDL, TG, UA (precipitate gout)
 Impotence; rash; photosensitivity
  K (uncommon at recommended dose),  Mg, Na
Potassium sparing diuretics – weak agents;  K
Loops diuretics – short acting;  K
Others
Arteriolar dilators:
 Hydralazine; minoxidil
 Peripheral vasodilationReflex tachycardia 
myocardial contractility  HA, palpitation and
fluid retention
 Given in combination with diuretics and BB

 Hydralazine – Lupus-like syndrome; GI

disturbance
 Minoxidil – Hirsutism; fluid retention
Monitoring of Treated HTN
Pressure controlled on a well-tolerated regimen
Infrequent follow-up and relevant blood tests
Check yearly blood lipids
Repeat ECG q2-4 yr
 More frequent if coronary risk factors present
“Step-down” therapy ( dosing or discontinuing
medications)
 In patients with modified life-style and excellent BP
control
Lack of responsiveness to Rx
Non-compliance
 Cost
 Improper instructions
 Inadequate patient education; memory deficits
 Side-effects
 Inconvenient dosing
Drug-related causes
 Too low dose
 Inappropriate combination
 Rapidly inactivation (hydralazine)
 Drug interac. (nasal decong., OCP, steroids, NSAIDS,
antidepressants, cocaine, cyclosporine, erythropietin)
Volume overload
 Na intake
 Fluid retention
 Inadequate diuretic therapy
 Progressive renal disease
Associated conditions
 Increasing obesity
 Alcohol intake (>1oz / day)
Secondary Hypertension
 Renal HTN; renal insufficiency
 Pheochromocytoma
 Primary aldosteronism
Psudohypertension
Hypertensive Emergency
Malignant HTN = HTN emergency
Potentially life-threatening
Rate of BP rise is critical
Elevated BP
 Without end-organ damage: HTN urgency
May be treated without IV medications;
BP should be reduced within a few hours
 With end-organ damage: HTN emergency
Immediate IV anti-hypertensives required;
BP should be reducd within 1 hour
New or progressive end-organ damage
 Papilledema; retinal hemorrhages
(blurring of vision)
 Acute myocardial ischemia or infarction

(Unstable angina; myocardial infarction)

 New-onset or worsening heart failure (Pulmonary
edema)
 Aortic dissection
 Proteinuria (frothy urine); hematuria; azotemia
 Encephalopathy (HA, irritability, confusion, AMS)
 TIA or stroke (intracranial hemorrhage)
Treatment
Treat immediately
 Minimize end-organ damage
ICU monitoring
IV anti-hypertensive medications
Goal is NOT immediate normotension
Do not lower blood pressure >25% in first 1-2 hr
and then toward 160/100 within 2-6 hr in order to
prevent Coronary, renal, cerebral ischemia
BP lowering medications retain sodium & water –
judicious concomitant use of diuretics
Medications
Nitroprusside
Hydralazine
Labetalol; esmolol
Nicardipine
Nitroglycerin