Heart Disease

TL;DR. The heart is a pump with its own small dedicated blood supply, the coronary arteries. Over decades, cholesterol-carrying particles lodge in the walls of those arteries and provoke an inflammatory response that builds a plaque. A plaque that narrows the artery causes chest pain on exertion (angina). A plaque that cracks open triggers a clot that blocks the artery completely, and the heart muscle downstream begins dying within minutes: a heart attack. Muscle that dies becomes scar, and enough scar produces heart failure, a pump that can no longer keep up. This chain is the single largest cause of death in the world, and nine modifiable factors account for about 90 percent of the risk of a first heart attack.

Key takeaways

• Ischaemic heart disease is the world's leading cause of death, responsible for roughly 13 percent of all deaths.
• Atherosclerosis is not passive clogging. It is an inflammatory disease of the artery wall in which LDL particles get trapped, are engulfed by immune cells, and build a lipid core under a fibrous cap.
• Most heart attacks come from moderate-sized plaques that rupture, not from the tightest narrowings. That is why a "clean stress test" is not a guarantee and why drugs that stabilise plaques save lives.
• A heart attack and a cardiac arrest are different events. One is a plumbing problem, the other an electrical one. The treatments share nothing.
• Time is muscle. Opening a blocked artery within the first hour or two saves most of the territory; after about 12 hours, the muscle is largely gone.
• Nine factors (lipids, smoking, hypertension, diabetes, abdominal obesity, stress, diet, exercise, alcohol) accounted for about 90 percent of population-attributable risk of first heart attack across 52 countries in the INTERHEART study.

What it is

In short: One label covering stable angina, acute coronary syndromes, heart failure, and atrial fibrillation, which interlock but are not the same thing.

"Heart disease" covers several distinct conditions that interlock.

Coronary artery disease (CAD), also called ischaemic heart disease, is narrowing of the arteries that supply the heart muscle. Its manifestations:

• Stable angina: chest pressure, tightness, or heaviness on exertion, relieved by rest within minutes. The artery supplies enough blood at rest and not enough under load.
• Acute coronary syndrome: a plaque ruptures and a clot forms. This includes unstable angina (pain at rest, no muscle death yet), NSTEMI (partial blockage, some muscle death), and STEMI (complete blockage, a characteristic ECG pattern, the classic full-thickness heart attack).
• Myocardial infarction (heart attack) is diagnosed by a rise in blood troponin, a protein released by dying heart muscle, together with evidence of ischaemia.

Heart failure is the pump failing to meet the body's demands, whether from scar after infarction, long-standing high blood pressure, valve disease, or damaged muscle.

Arrhythmias are electrical disorders, most importantly atrial fibrillation.

Don't be confused: a heart attack is not a cardiac arrest. A heart attack is a blocked coronary artery starving muscle of oxygen; the person is usually conscious, in pain, and needs the artery opened. A cardiac arrest is the heart's electrical activity collapsing into a rhythm that pumps no blood; the person is unconscious, not breathing normally, and needs CPR and a defibrillator within minutes. A heart attack can cause a cardiac arrest, which is the main way heart attacks kill people before they reach hospital. Chest compressions are useless for a conscious person with chest pain and are the only thing that matters for someone in arrest.

The history

In short: The disease became understandable in 1912, survivable in the 1960s with coronary care units, and largely preventable once statins and risk factor control arrived.

Chest pain on exertion was described precisely by William Heberden in 1768, who named it angina pectoris without knowing its cause. The connection to blocked coronary arteries was suspected through the 1800s and established for clinical purposes by James Herrick in 1912, who described the syndrome of coronary thrombosis in living patients rather than at autopsy. For decades the treatment was bed rest for six weeks.

The modern picture assembled in the second half of the twentieth century:

Age-adjusted death rates from coronary disease in high-income countries have fallen by more than half since the 1970s. Roughly half of that fall is attributed to risk factor change (mostly smoking and cholesterol) and roughly half to treatments.

What actually goes wrong

In short: LDL particles get trapped in the artery wall and provoke an inflammatory plaque, and most heart attacks come from moderate plaques that rupture rather than from the tightest narrowings.

Atherosclerosis, step by step

1. Injury and entry. The artery lining (endothelium) is damaged by high blood pressure, smoke chemicals, high glucose, or turbulent flow at branch points. Injury makes it permeable and sticky.
2. Retention. LDL particles carrying cholesterol pass into the artery wall. The key event is that they are retained there, bound to the wall matrix. The more LDL particles in the blood, the more get trapped, which is why particle count (measured as apolipoprotein B, one per particle) predicts risk slightly better than cholesterol concentration.
3. Oxidation and alarm. Trapped LDL is chemically modified and the immune system treats it as damage.
4. Foam cells. Monocytes enter the wall, become macrophages, engulf the modified LDL, and become lipid-stuffed foam cells. Enough of them form a visible fatty streak, present in the arteries of many teenagers.
5. Plaque. Smooth muscle cells migrate over the lesion and lay down a fibrous cap over a soft core of lipid and dead cells. This is a mature atherosclerotic plaque.
6. Rupture. Inflammation inside the plaque thins the cap. When it tears, the thrombogenic core is exposed to flowing blood, platelets pile on, and a clot forms in minutes.

Step 6 explains the most counterintuitive fact in cardiology. Most heart attacks arise from plaques that were narrowing the artery by less than 70 percent, because soft-cored, thin-capped plaques are more rupture-prone than old, calcified, tight ones. That is why treating a tight narrowing with a stent relieves symptoms without necessarily preventing future heart attacks, and why drugs that lower LDL and calm inflammation across the whole arterial tree do prevent them.

Cholesterol, briefly and correctly

Cholesterol is essential: it is a component of every cell membrane and the precursor of steroid hormones and vitamin D. It is not water-soluble, so it travels in lipoprotein particles.

The causal role of LDL is one of the best-established facts in medicine, supported by randomised drug trials, by inherited conditions with very high LDL (familial hypercholesterolaemia, causing heart attacks in the thirties and forties), and by inherited variants that lower LDL for life and confer large reductions in heart disease.

Heart failure

When muscle dies or is chronically overloaded, the heart pumps less effectively. The body responds as though to blood loss: the sympathetic nervous system and the RAAS activate, retaining salt and water and constricting vessels. In the short term this maintains blood pressure. Sustained, it makes everything worse, driving fluid overload and further remodelling of the heart. This neurohormonal insight is why the drugs that improve survival in heart failure are ones that block those systems, not ones that stimulate the heart to beat harder.

Two forms:

• HFrEF (reduced ejection fraction): the ventricle is weak and dilated, ejecting under 40 percent of its volume per beat. Best treated, with four drug classes proven to extend life.
• HFpEF (preserved ejection fraction): the ventricle is stiff and fills poorly, often from hypertension, obesity, diabetes, and ageing. Roughly half of all heart failure, more common in women and older patients, and until recently without proven treatments.

Symptoms of both: breathlessness on exertion and lying flat, ankle swelling, fatigue, waking at night short of breath.

Atrial fibrillation

The atria (the heart's upper chambers) lose coordinated contraction and quiver at 300 to 600 impulses per minute, of which the ventricle receives an irregular subset. Two consequences. The pulse becomes irregular and often fast, which can cause palpitations, breathlessness, and, over time, a weakened heart. And blood pools in the left atrial appendage, forms a clot, and that clot can travel to the brain. Atrial fibrillation increases stroke risk roughly fivefold, and the strokes it causes are more severe than average.

What it does to the body

In short: Muscle starts dying within half an hour, becomes scar, and leaves both a weaker pump and an electrically unstable region.

• Angina limits activity, sometimes severely, without necessarily damaging muscle.
• A heart attack kills muscle at a rate that depends on collateral supply. Irreversible damage begins within about 20 to 30 minutes and is largely complete within 6 to 12 hours. The dead area becomes fibrous scar over weeks.
• Scar produces two long-term problems: a weaker pump (heart failure) and an electrically unstable region that can generate lethal arrhythmias.
• Sudden cardiac death is often the first presentation of coronary disease. A substantial share of people who die of a heart attack die before reaching hospital.
• The same disease elsewhere: the identical process in leg arteries causes peripheral artery disease (pain on walking, poor healing, gangrene in the extreme); in the neck and brain arteries it causes stroke (Chapter 22); in the kidney arteries it causes renal impairment. This is why a patient with one is screened for the others.

Is it deadly?

In short: The world's single leading cause of death, though survival after a heart attack has improved several-fold since the pre-coronary-care era.

Ischaemic heart disease is the leading single cause of death worldwide, responsible for around 13 percent of all deaths, roughly 9 million a year. Cardiovascular disease as a whole (heart disease plus stroke plus the rest) accounts for approximately 17 to 20 million deaths annually, about a third of all deaths.

The individual picture is better than those numbers suggest, and improving:

• In-hospital mortality after a STEMI has fallen from roughly 30 percent in the pre-coronary-care era to under 5 to 7 percent where primary angioplasty is available promptly.
• Out-of-hospital cardiac arrest survival to discharge remains poor, roughly 8 to 12 percent overall, and is several times higher when a bystander performs CPR and a defibrillator is used quickly.
• Heart failure carries a prognosis comparable to many cancers: roughly half of patients die within five years of diagnosis, though modern four-drug therapy has changed that trajectory substantially for HFrEF.

Is it contagious?

No. Atherosclerosis cannot be caught.

Three genuine connections to infection are worth knowing, because they get garbled. Rheumatic heart disease is caused by an infection: untreated streptococcal throat infection can trigger an autoimmune attack on heart valves, and it remains a major cause of valve disease in low-income countries, entirely preventable with antibiotics. Infective endocarditis is a bacterial infection of the heart valves themselves. And acute infections trigger heart attacks: influenza and COVID-19 measurably raise the risk of myocardial infarction in the weeks after infection, through inflammation and increased clotting. That last point is why influenza vaccination is recommended for people with heart disease and reduces cardiovascular events in trials.

Who gets it

In short: Nine modifiable factors account for roughly 90 percent of first heart attacks worldwide, and women are systematically diagnosed later than men.

Age and sex. Risk rises steeply with age. Men develop coronary disease roughly 7 to 10 years earlier than women on average, and the gap narrows after menopause. Women's heart disease is systematically underdiagnosed: symptoms more often include breathlessness, nausea, fatigue, and jaw or back discomfort rather than crushing central chest pain, and women are less likely to receive prompt angiography and guideline treatment. Heart disease kills more women than all cancers combined in most high-income countries.

The nine factors. The INTERHEART case-control study across 52 countries found that abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial stress, low fruit and vegetable intake, physical inactivity, and alcohol together accounted for about 90 percent of the population-attributable risk of a first heart attack, consistently across regions, ethnicities, and both sexes. The pattern is not a Western phenomenon.

Genetics. Family history of early heart disease is a real independent risk factor. Specific high-impact conditions: familial hypercholesterolaemia, affecting roughly 1 in 250 people, causing lifelong very high LDL and premature heart disease, badly underdiagnosed. Elevated lipoprotein(a), affecting about 1 in 5, genetically fixed, and only now becoming treatable.

Geography. Age-standardised cardiovascular mortality has fallen substantially in Western Europe, North America, Japan, and Australasia, and is high and in some places rising in Eastern Europe, Central Asia, South Asia, and parts of sub-Saharan Africa. South Asian populations develop coronary disease earlier and at lower BMI. Over three quarters of cardiovascular deaths now occur in low- and middle-income countries.

Treatment, and how it works

In short: Open the blocked artery as fast as possible, then lower LDL, blood pressure, and clotting for life, with four specific drug classes for heart failure.

The acute heart attack

The objective is to restore flow as fast as possible.

• Aspirin, chewed immediately, irreversibly blocks platelet COX-1 and reduces further clotting. ISIS-2 showed aspirin alone cut deaths by about 23 percent.
• A second antiplatelet drug (ticagrelor, clopidogrel, prasugrel) blocks a different platelet activation pathway.
• Primary percutaneous coronary intervention (PCI): a catheter is passed from the wrist or groin to the blocked artery, a balloon opens it, and a stent (a metal mesh tube, usually coated with a drug that prevents scar tissue regrowth) holds it open. This is the preferred treatment when it can be delivered quickly.
• Thrombolysis: clot-dissolving drugs, used where PCI cannot be reached in time. Effective, with a small risk of causing bleeding including in the brain.
• Oxygen only if oxygen levels are low, morphine for pain, and beta blockers and nitrates as appropriate.

The controlling variable is time. "Door-to-balloon" targets of under 90 minutes exist because the amount of muscle saved falls steeply with delay, and most of the delay in practice is the patient's, not the hospital's. This is why public campaigns focus on calling emergency services immediately rather than driving to hospital or waiting to see whether it passes.

Long-term prevention after a diagnosis

Revascularisation for stable disease

For stable angina, the ISCHEMIA trial randomised patients with moderate or severe ischaemia to an invasive strategy (angiography plus stenting or bypass) or optimal medical therapy alone, and found no reduction in death or heart attack from the invasive approach, though it did relieve angina better. The practical conclusion: stents relieve symptoms; drugs and risk factor control prevent events. Bypass surgery retains an advantage in specific anatomies, notably left main disease, multivessel disease with diabetes, and reduced pump function.

Heart failure

The four pillars for HFrEF, each shown to reduce mortality, and used together:

1. ARNI (sacubitril/valsartan) or an ACE inhibitor/ARB: blocks RAAS and, in the ARNI case, also boosts protective natriuretic peptides.
2. Beta blocker (bisoprolol, carvedilol, metoprolol succinate): blocks chronic sympathetic overdrive.
3. Mineralocorticoid receptor antagonist (spironolactone, eplerenone): blocks aldosterone-driven fibrosis and fluid retention.
4. SGLT2 inhibitor (dapagliflozin, empagliflozin): originally a diabetes drug, now proven in heart failure with and without diabetes, through mechanisms still being worked out.

Plus diuretics for symptoms (they relieve fluid overload without extending life), implantable defibrillators for those at high arrhythmic risk, cardiac resynchronisation pacing for specific conduction patterns, and in end-stage disease, left ventricular assist devices and transplantation.

For HFpEF, SGLT2 inhibitors are the first class with clear benefit, and treating the drivers (blood pressure, weight, atrial fibrillation, sleep apnoea) is central.

Atrial fibrillation

Three separate decisions. Anticoagulation to prevent stroke, guided by a risk score (CHA2DS2-VASc); direct oral anticoagulants (apixaban, rivaroxaban, edoxaban, dabigatran) have largely replaced warfarin, with less intracranial bleeding and no routine monitoring. Rate control with beta blockers or diltiazem. Rhythm control with antiarrhythmic drugs or catheter ablation, which burns or freezes the tissue around the pulmonary veins where the abnormal impulses usually originate; early rhythm control improves outcomes compared with delaying it.

Note the logic: anticoagulation is decided by stroke risk, not by how much the fibrillation bothers the patient. Someone whose AF is silent still needs the anticoagulant.

What treatment costs

In short: Every antithrombotic trades clots for bleeding, and most statin muscle symptoms turn out to be nocebo effects under blinded testing.

• Statins. Muscle aches are the common complaint; blinded n-of-1 trials (SAMSON) and randomised re-challenge studies find symptom rates on statin and placebo nearly identical, meaning most attributed symptoms are nocebo effects, though individual intolerance is real. Serious muscle injury (rhabdomyolysis) is rare, roughly 1 to 3 per 100,000 patient-years. A small increase in new type 2 diabetes diagnoses exists and is outweighed by cardiovascular benefit in those at risk.
• Antiplatelets and anticoagulants. All of them trade clot prevention for bleeding risk. That trade is favourable after a heart attack or in atrial fibrillation with meaningful stroke risk, and unfavourable in low-risk people, which is why routine aspirin for primary prevention has been withdrawn from most guidelines.
• Beta blockers. Fatigue, cold extremities, reduced peak exercise capacity.
• PCI. Bleeding at the access site, contrast-induced kidney injury, rare stent thrombosis, and the requirement for months of dual antiplatelet therapy afterwards.
• Bypass surgery. A major operation with a small mortality risk, stroke risk, and measurable cognitive effects in some patients, in exchange for durable revascularisation.

What the person can do

In short: Stopping smoking outperforms any single drug, and cardiac rehabilitation is a treatment rather than an optional extra.

The lifestyle evidence here is stronger than in almost any other chapter.

• Stop smoking. The single highest-yield action. Excess coronary risk falls sharply within the first year and approaches that of a never-smoker over 10 to 15 years. It is more effective than any single drug.
• Cardiac rehabilitation. A structured supervised exercise and education programme after a heart attack reduces cardiovascular mortality and hospitalisation. It is underused everywhere, with participation often under half of eligible patients.
• Exercise. 150 minutes a week of moderate activity, or 75 of vigorous, plus resistance work. Benefit appears well below those targets, and the largest gain is from sedentary to slightly active.
• Diet. The PREDIMED trial randomised people at high cardiovascular risk to a Mediterranean diet supplemented with extra virgin olive oil or nuts, or to a low-fat control, and found roughly 30 percent fewer major cardiovascular events in the Mediterranean groups. The practical core: more olive oil, nuts, vegetables, legumes, fish, and whole grains; less processed meat, refined carbohydrate, and sugary drinks.
• Control blood pressure and diabetes, per their chapters.
• Know the symptoms and act. Chest discomfort lasting more than a few minutes, with or without radiation to arm, jaw, or back, breathlessness, sweating, or nausea: call emergency services. Chew an aspirin unless told otherwise. Do not drive yourself.
• Learn CPR. Bystander CPR roughly doubles to triples survival from out-of-hospital cardiac arrest, and compression-only CPR is effective and easy to learn.

Living with it

After a heart attack, the psychological load is substantial: depression affects roughly a fifth of patients and independently predicts worse outcomes. Fear of exertion is common and usually the opposite of what is needed, which is one of the things supervised rehabilitation exists to correct. Return to work, driving, and sexual activity all have straightforward guidance that patients frequently do not receive unless they ask.

Heart failure imposes a different burden: daily weights, fluid and salt limits, multiple medications, and a fluctuating course punctuated by hospital admissions. Advance care planning has more value here than in most chronic diseases, because the trajectory is unpredictable and the last decline can be rapid.

What's next

• Lipoprotein(a) lowering. Pelacarsen, olpasiran, and related RNA therapies reduce Lp(a) by 80 percent or more; outcome trials are reporting through the mid-2020s and will determine whether this fixed genetic risk factor becomes modifiable.
• Gene editing. A single infusion base-editing the PCSK9 gene in the liver has entered early human trials, aiming at permanent LDL reduction from one treatment.
• Anti-inflammatory therapy. CANTOS showed that an antibody against interleukin-1beta cut cardiovascular events without changing lipids, proving inflammation is an independent target; cheaper agents such as colchicine now carry that idea into practice.
• AI on the ECG, detecting reduced pump function, valve disease, and future atrial fibrillation from an ordinary tracing.
• Polypills and population-level lipid and blood pressure control, which is where the largest global gains remain available.

Sources and notes

Global mortality figures are WHO Global Health Estimates and Global Burden of Disease data; ischaemic heart disease is consistently the leading cause of death at around 13 percent of the global total. INTERHEART: Yusuf et al., The Lancet, 2004. ISIS-2: The Lancet, 1988. Statin effect per 1 mmol/L: Cholesterol Treatment Trialists' Collaboration meta-analyses. ISCHEMIA: Maron et al., NEJM, 2020. PREDIMED: Estruch et al., NEJM, 2013 and 2018 (republished after correction of randomisation irregularities in some sites; the main conclusion was retained). CANTOS: Ridker et al., NEJM, 2017. SAMSON: Howard et al., JACC, 2021. Heart failure four-pillar therapy: PARADIGM-HF, DAPA-HF, EMPEROR-Reduced, RALES, and related trials. Rhabdomyolysis incidence and familial hypercholesterolaemia prevalence (about 1 in 250) are commonly cited literature estimates. Out-of-hospital cardiac arrest survival figures vary widely by registry and region.

Open questions. The optimal LDL target ("how low is too low") has moved steadily downward without a floor being found. Treatment of HFpEF remains far less effective than for HFrEF. Whether Lp(a) lowering translates into event reduction is not yet known.

Next: the same vascular disease, in the organ least able to tolerate it. 👉