Cardiovascular Diseases - Comprehensive Overview

Cardiovascular diseases (CVD) encompass a broad range of disorders affecting the heart and blood vessels. They represent the leading cause of death globally, accounting for approximately 17.9 million deaths annually. This article provides a comprehensive overview of major cardiovascular conditions, their pathophysiology, clinical presentation, diagnostic approaches, and treatment strategies.

Atherosclerosis

Atherosclerosis is a chronic inflammatory disease characterized by the buildup of plaques within arterial walls. It serves as the underlying pathology for most cardiovascular events.

Pathophysiology

Stage	Description	Key Cells/Mediators
Endothelial injury	Dysfunction of vascular endothelium due to shear stress, toxins (smoking), hypertension, hyperglycemia, or hyperlipidemia	Endothelial cells
LDL infiltration	Apolipoprotein B-containing lipoproteins penetrate the endothelium and become trapped in the intima	LDL, VLDL
Oxidation and modification	LDL undergoes oxidative modification by reactive oxygen species	ROS, myeloperoxidase
Monocyte recruitment	Endothelial cells express adhesion molecules (VCAM-1, ICAM-1) promoting monocyte adhesion and diapedesis	Monocytes, MCP-1, selectins
Foam cell formation	Macrophages engulf oxidized LDL via scavenger receptors (SR-A, CD36) becoming foam cells	Macrophages, scavenger receptors
Fatty streak formation	Accumulation of foam cells in the intima — earliest visible lesion	Foam cells, T-lymphocytes
Fibrous plaque development	Smooth muscle cells migrate from media to intima, proliferate, and produce extracellular matrix (collagen, elastin) forming a fibrous cap	Smooth muscle cells, PDGF, TGF-beta
Complicated plaque	Plaque rupture or erosion leading to thrombus formation	Platelets, tissue factor, fibrin

Risk Factors

Modifiable Risk Factors	Non-Modifiable Risk Factors
Hypertension	Age (>45 men, >55 women)
Hyperlipidemia	Male sex
Smoking	Family history of premature CVD
Diabetes mellitus	Genetic predisposition
Obesity (BMI >30)
Physical inactivity
Unhealthy diet (high saturated fat, trans fat, sodium)
Excessive alcohol consumption
Chronic kidney disease
Psychosocial stress

Clinical Manifestations by Vascular Territory

Vascular Territory	Resulting Condition
Coronary arteries	Stable angina, acute coronary syndrome (UA/NSTEMI/STEMI)
Carotid/cerebral arteries	Transient ischemic attack, ischemic stroke
Aorta	Aortic aneurysm, aortic dissection
Renal arteries	Renovascular hypertension, renal ischemia
Mesenteric arteries	Chronic mesenteric ischemia, acute mesenteric ischemia
Peripheral arteries (lower extremities)	Peripheral artery disease (claudication, critical limb ischemia)

Coronary Artery Disease (CAD)

CAD results from atherosclerotic obstruction of coronary arteries, leading to myocardial ischemia.

Grading of Angina

Class (CCS)	Description
I	Ordinary physical activity does not cause angina; angina with strenuous, rapid, or prolonged exertion
II	Slight limitation; angina with walking >2 blocks or climbing >1 flight of stairs
III	Marked limitation; angina with walking 1-2 blocks or climbing 1 flight of stairs
IV	Inability to perform any physical activity without discomfort; angina may be present at rest

Myocardial Infarction (MI)

MI occurs when acute myocardial ischemia leads to cardiomyocyte necrosis. It is classified by ECG findings into STEMI and NSTEMI.

STEMI vs NSTEMI Comparison

Feature	STEMI	NSTEMI
ECG finding	ST-segment elevation in contiguous leads	ST-segment depression, T-wave inversion, or non-specific changes
Extent of infarction	Transmural (full thickness)	Subendocardial (partial thickness)
Occlusion type	Complete (usually thrombotic)	Subtotal or intermittent
Biomarker elevation	Significant rise (troponin, CK-MB)	Elevated but may be lower
Time to peak troponin	12-24 hours	Variable
Urgency of revascularization	Emergent (door-to-balloon <90 min)	Urgent (within 24-48 hours typically)
Typical causative artery	LAD, RCA, or circumflex with near-100% occlusion	Same arteries but with subtotal occlusion
Complications	More arrhythmias, mechanical complications	Recurrent ischemia, progression to STEMI

Universal Definition of MI (Fourth Universal Definition)

Type	Description
Type 1	Spontaneous MI related to atherosclerotic plaque rupture, fissure, or erosion
Type 2	MI secondary to supply-demand mismatch (e.g., hypotension, tachycardia, anemia, hypertension)
Type 3	Sudden cardiac death with symptoms suggestive of MI but no biomarkers available
Type 4a	MI associated with PCI
Type 4b	MI associated with stent thrombosis
Type 5	MI associated with CABG

Diagnostic Criteria for MI

Acute MI is diagnosed with: Rise and/or fall of cardiac troponin with at least one value >99th percentile URL AND at least one of:

• Symptoms of myocardial ischemia
• New ischemic ECG changes (ST-T changes, new LBBB, Q waves)
• Imaging evidence of new loss of viable myocardium or new wall motion abnormality
• Intracoronary thrombus on angiography

Cardiac Biomarkers

Biomarker	Onset	Peak	Return to Normal	Specificity
High-sensitivity troponin (hs-cTnI/T)	2-4 hours	12-24 hours	5-14 days	High (cardiac-specific)
Conventional troponin	3-6 hours	12-24 hours	5-14 days	High
CK-MB	3-6 hours	12-24 hours	48-72 hours	Moderate
Myoglobin	1-3 hours	6-12 hours	24-36 hours	Low

Treatment of STEMI

Phase	Interventions
Pre-hospital	Aspirin 324 mg chewed, nitroglycerin, oxygen if saturations <90%, pain management (morphine)
Reperfusion (primary PCI)	Door-to-balloon time <90 minutes; dual antiplatelet therapy (aspirin + P2Y12 inhibitor), anticoagulation (heparin/bivalirudin)
Reperfusion (fibrinolysis)	When PCI not available within 120 minutes; tenecteplase, alteplase, reteplase
Adjunctive pharmacotherapy	Beta-blockers, ACE inhibitors/ARBs, statins (high-intensity), aldosterone antagonists (if EF <40%)
Long-term management	Dual antiplatelet therapy (3-12 months), then aspirin indefinitely; high-intensity statin; beta-blocker; ACE inhibitor/ARB; cardiac rehabilitation

Heart Failure

Heart failure is a complex syndrome in which the heart cannot pump sufficient blood to meet metabolic demands.

HFrEF vs HFpEF

Parameter	HFrEF (Heart Failure with Reduced Ejection Fraction)	HFpEF (Heart Failure with Preserved Ejection Fraction)
Left ventricular ejection fraction (LVEF)	<40%	>=50% (HFmrEF: 41-49%)
Ventricular size	Dilated (eccentric remodeling)	Normal or mildly increased (concentric remodeling)
Wall thickness	Normal or decreased	Increased
Diastolic function	Impaired (usually)	Impaired (primary abnormality)
Systolic function	Impaired	Preserved
Primary pathophysiology	Loss of contractile function	Impaired relaxation, increased stiffness
Typical patient	Younger, male, prior MI	Older, female, hypertension, obesity, diabetes
Neurohormonal activation	Prominent	Variable
Response to neurohormonal antagonists	Well-established benefit	Limited evidence
Hospitalization rate	High	High
Mortality	High (declining with treatment)	High (similar to HFrEF)

NYHA Functional Classification

Class	Description
I	No limitation of physical activity; ordinary activity does not cause symptoms
II	Slight limitation; comfortable at rest but ordinary physical activity results in fatigue, dyspnea, or palpitations
III	Marked limitation; comfortable at rest but less than ordinary activity causes symptoms
IV	Unable to carry out any physical activity without discomfort; symptoms at rest

ACC/AHA Staging

Stage	Description
A	High risk for HF but no structural disease or symptoms (hypertension, diabetes, CAD, cardiotoxic exposure)
B	Structural heart disease but no signs or symptoms (LV hypertrophy, prior MI, valvular disease)
C	Structural heart disease with prior or current symptoms (dyspnea, fatigue, edema)
D	Refractory HF requiring specialized interventions (LVAD, transplant, continuous inotropes)

Pharmacotherapy for HFrEF

Drug Class	Examples	Mechanism	Mortality Benefit
ACE inhibitors	Enalapril, lisinopril, ramipril	Block angiotensin II production	Yes
ARBs	Losartan, valsartan, candesartan	Block angiotensin II receptor	Yes
Beta-blockers	Carvedilol, metoprolol succinate, bisoprolol	Block sympathetic activation	Yes
Aldosterone antagonists	Spironolactone, eplerenone	Block aldosterone receptor	Yes
ARNI (neprilysin inhibitor + ARB)	Sacubitril/valsartan	Enhance natriuretic peptides + block AT1	Yes (superior to ACE)
SGLT2 inhibitors	Dapagliflozin, empagliflozin	Block renal glucose reabsorption	Yes
Ivabradine	Ivabradine	Inhibits If current in SA node	Yes (certain patients)
Digoxin	Digoxin	Na/K-ATPase inhibitor	No mortality benefit; reduces hospitalization
Diuretics	Furosemide, torsemide	Loop diuretics	Symptom relief only

HFpEF Treatment Challenges

• No therapy has definitively reduced mortality in HFpEF
• Diuretics for volume management
• Treat underlying conditions: hypertension, diabetes, obesity, atrial fibrillation
• SGLT2 inhibitors show promise (EMPEROR-Preserved, DELIVER trials)
• Exercise training improves functional capacity

Arrhythmias

Classification of Arrhythmias

Category	Examples
Supraventricular tachyarrhythmias	Sinus tachycardia, atrial fibrillation, atrial flutter, AV nodal reentrant tachycardia (AVNRT), AV reentrant tachycardia (AVRT, WPW), atrial tachycardia
Ventricular tachyarrhythmias	Ventricular tachycardia (monomorphic, polymorphic), ventricular fibrillation, torsades de pointes
Bradyarrhythmias	Sinus bradycardia, sick sinus syndrome, AV block (1st, 2nd, 3rd degree)
Conduction abnormalities	Bundle branch block (LBBB, RBBB), fascicular block

Atrial Fibrillation (AFib)

Parameter	Detail
Definition	Rapid, irregular atrial activation with loss of coordinated atrial contraction
ECG characteristics	Absent P waves, irregularly irregular ventricular rate, fibrillatory baseline
Prevalence	~2-3% of general population; increases with age (>10% in those >80 years)
Risk factors	Hypertension, valvular disease, HF, CAD, obesity, OSA, alcohol, hyperthyroidism
Classification	Paroxysmal (<7 days, self-terminating), Persistent (>7 days, requiring cardioversion), Long-standing persistent (>12 months), Permanent (accepted)
Complications	Ischemic stroke (5-fold increase), HF, cognitive decline
Stroke risk assessment	CHA2DS2-VASc score
Bleeding risk assessment	HAS-BLED score

CHA2DS2-VASc Score

Risk Factor	Points
C - Congestive heart failure	1
H - Hypertension	1
A2 - Age >=75 years	2
D - Diabetes mellitus	1
S2 - Stroke/TIA/thromboembolism	2
V - Vascular disease (CAD, PAD, aortic plaque)	1
A - Age 65-74 years	1
Sc - Sex category (female)	1

Anticoagulation recommendation: If CHA2DS2-VASc >=2 in men or >=3 in women, recommend long-term anticoagulation.

Ventricular Tachycardia (VT) and Ventricular Fibrillation (VF)

Feature	Monomorphic VT	Polymorphic VT	VF
ECG	Wide QRS (>120ms), uniform morphology, rate >100/min	Wide QRS, changing morphology, rate >100/min	Chaotic, irregular rhythm with no identifiable QRS complexes
Mechanism	Reentry (usually around scar)	Reentry (ischemia, channelopathy)	Multiple reentrant wavelets
Hemodynamic stability	May be stable or unstable	Usually unstable	Always unstable (no cardiac output)
Causes	Old MI scar, cardiomyopathy, channelopathies	Acute ischemia, electrolyte abnormalities, long QT syndrome	Acute MI, ischemia, cardiomyopathy
Treatment (stable)	Antiarrhythmics (amiodarone, procainamide), ablation	Correct ischemia/electrolytes, magnesium, beta-blockers	Immediate defibrillation
Treatment (unstable)	Synchronized cardioversion	Synchronized cardioversion	Defibrillation (unsynchronized)

Valvular Heart Disease

Valve	Stenosis	Regurgitation
Aortic	Aortic stenosis (AS): Pressure overload, LV hypertrophy, angina, syncope, HF; most common valvular disease in developed countries	Aortic regurgitation (AR): Volume overload, LV dilation, bounding pulses, wide pulse pressure
Mitral	Mitral stenosis (MS): Usually rheumatic, left atrial enlargement, AFib, pulmonary hypertension	Mitral regurgitation (MR): Most common cause is mitral valve prolapse; volume overload, left atrial and LV enlargement
Tricuspid	Tricuspid stenosis: Rare, usually rheumatic	Tricuspid regurgitation: Usually functional from right ventricular dilation; peripheral edema, ascites
Pulmonary	Pulmonary stenosis: Usually congenital	Pulmonary regurgitation: Usually from pulmonary hypertension

Severity Grading (Aortic Stenosis Example)

Parameter	Mild	Moderate	Severe
Peak velocity (m/s)	2.0-2.9	3.0-3.9	>=4.0
Mean gradient (mmHg)	<20	20-39	>=40
Aortic valve area (cm2)	>1.5	1.0-1.5	<1.0
Indexed AVA (cm2/m2)	>0.85	0.60-0.85	<0.6

Peripheral Artery Disease (PAD)

Feature	Detail
Definition	Atherosclerotic occlusion of arteries supplying the lower extremities
Prevalence	~8-10% of population >60 years
Classic symptom	Intermittent claudication (cramping pain in calves/ thighs with walking, relieved by rest)
Atypical presentations	Leg pain with walking that does not force stop, leg pain at rest, numbness, weakness
Critical limb ischemia	Rest pain, non-healing ulcers, gangrene
Ankle-brachial index (ABI)	Normal: 1.0-1.4; PAD: <0.9; Severe PAD: <0.5
Treatment	Exercise therapy, smoking cessation, antiplatelet therapy (aspirin/clopidogrel), statins, cilostazol, revascularization (angioplasty/stenting, bypass)

Hypertension

Category	Systolic (mmHg)	Diastolic (mmHg)
Normal	<120	and <80
Elevated	120-129	and <80
Hypertension Stage 1	130-139	or 80-89
Hypertension Stage 2	>=140	or >=90
Hypertensive crisis	>=180	and/or >=120

Antihypertensive Drug Classes

Class	Examples	Key Indications	Side Effects
Thiazide diuretics	Chlorthalidone, HCTZ	First-line (African American, elderly)	Hypokalemia, hyponatremia, hyperglycemia, hyperuricemia
ACE inhibitors	Lisinopril, enalapril, ramipril	First-line (diabetes, CKD, HF, post-MI)	Cough, angioedema, hyperkalemia, renal impairment
ARBs	Losartan, valsartan, candesartan	First-line (intolerant to ACE)	Hyperkalemia, renal impairment (less cough)
Calcium channel blockers (dihydropyridine)	Amlodipine, nifedipine	First-line (African American, elderly)	Peripheral edema, headache, reflex tachycardia
Calcium channel blockers (non-dihydropyridine)	Verapamil, diltiazem	Rate control in AFib, angina	Bradycardia, constipation (verapamil)
Beta-blockers	Metoprolol, atenolol, carvedilol	Post-MI, HF, angina	Bradycardia, fatigue, bronchospasm
Aldosterone antagonists	Spironolactone, eplerenone	Resistant HTN, HF	Hyperkalemia, gynecomastia (spironolactone)
Alpha-blockers	Doxazosin, terazosin	BPH (adjunct for HTN)	Orthostatic hypotension
Direct vasodilators	Hydralazine, minoxidil	Resistant HTN (3rd/4th line)	Reflex tachycardia, lupus-like (hydralazine), hirsutism (minoxidil)

Stroke

Ischemic vs Hemorrhagic Stroke

Feature	Ischemic Stroke	Hemorrhagic Stroke
Frequency	~87% of all strokes	~13% of all strokes
Cause	Thrombotic or embolic occlusion of cerebral artery	Rupture of cerebral blood vessel
Subtypes	Large artery atherosclerosis, cardioembolic (AFib), small vessel (lacunar), cryptogenic, other (dissection, vasculitis)	Intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH)
Pathophysiology	Sudden loss of blood flow leads to ischemic core (irreversibly damaged) and penumbra (salvageable tissue)	Blood in brain parenchyma or subarachnoid space causes mass effect, increased ICP, neurotoxicity
Peak incidence	Older age (increases >65)	Similar but ICH more common in Asian/African populations
Acute management	IV tPA (within 4.5 hours), mechanical thrombectomy (within 6-24 hours depending on selection criteria)	Blood pressure control, reversal of anticoagulation, surgical evacuation (if indicated), aneurysm clipping/coiling (for SAH)

Stroke Symptoms (FAST mnemonic)

Sign	Description
F - Facial drooping	One side of face droops or is numb; ask person to smile
A - Arm weakness	One arm drifts downward when both are raised
S - Speech difficulty	Slurred speech or inability to speak/understand
T - Time to call emergency	Note time of onset, call emergency services immediately

Stroke Prevention Strategies

Strategy	Detail
Primary prevention	BP control, statin therapy, glycemic control, smoking cessation, exercise, healthy diet
Secondary prevention (antiplatelet)	Aspirin, clopidogrel, or aspirin + dipyridamole (for non-cardioembolic ischemic stroke)
Secondary prevention (anticoagulation)	Warfarin, DOACs (apixaban, rivaroxaban, edoxaban, dabigatran) for AFib-related stroke
Carotid revascularization	CEA or CAS for symptomatic carotid stenosis >50% or asymptomatic >70-80%
Lifestyle	Mediterranean diet, regular exercise, weight management, limited alcohol