Cardiovascular disease

Ischaemic heart disease and stroke account for most of the burden. In 2019, ischaemic heart disease caused 9.14 million deaths and affected 197 million people worldwide, and stroke caused 6.55 million deaths and affected 101 million people [1]. The same analysis tracked 13 underlying causes of cardiovascular death in all, and found that the number of years lived with disability from cardiovascular disease doubled between 1990 and 2019 [1].

Heart failure is a state in which the heart cannot pump enough blood to meet the body's needs; it is usually the end result of another cardiovascular condition such as a previous heart attack or long-standing high blood pressure. Peripheral artery disease is the narrowing of arteries outside the heart and brain, most often in the legs, by the same process that narrows the coronary arteries. Although the forms differ in the organ affected, most share atherosclerosis as the underlying cause and a common set of risk factors.

Atherosclerosis is the gradual build-up of plaque, a deposit of cholesterol, immune cells and scar tissue, inside the walls of arteries. Cholesterol enters the artery wall only inside lipoprotein particles that carry apolipoprotein B (apoB), mainly LDL; once trapped in the wall, these particles set off an inflammatory response that enlarges the plaque. The number of apoB particles in the blood largely determines how many enter and are retained in the artery wall [7]. A heart attack or ischaemic stroke usually occurs when a plaque ruptures and a blood clot forms on it, blocking the artery.

A 2017 consensus statement of the European Atherosclerosis Society reviewed genetic studies, more than 200 prospective studies, Mendelian randomisation studies (which use naturally occurring gene variants as a natural experiment) and randomised trials, together covering more than 2 million participants and more than 150,000 cardiovascular events. It concluded that LDL causes atherosclerotic cardiovascular disease and that risk rises with both the level of LDL cholesterol and the length of time the arteries are exposed to it [8]. The process is described in more detail under cholesterol.

High blood pressure damages the inner lining of arteries and accelerates plaque formation, and smoking promotes both plaque growth and clotting. Inflammation also contributes. In the CANTOS trial of 10,061 patients with a previous heart attack, the anti-inflammatory antibody canakinumab at 150 mg every three months lowered the rate of recurrent heart attack, stroke or cardiovascular death (hazard ratio 0.85) without changing cholesterol levels, but it increased fatal infections and did not change overall mortality [9]. The role of chronic inflammation in aging is covered under inflammation.

The INTERHEART study compared 15,152 people with a first heart attack with 14,820 controls in 52 countries on every inhabited continent. It reported odds ratios (how much more common an exposure was among patients than among controls, after adjustment) and the population attributable risk of each factor. A raised ratio of apoB to apoA1 (a measure of harmful relative to protective lipoproteins), current smoking, diabetes, psychosocial stress and a history of hypertension showed the strongest associations, while daily fruit and vegetables, regular physical activity and regular alcohol intake were associated with lower risk. The associations held in men and women, at all ages and in every region [2].

The American Heart Association's Life's Essential 8 score combines eight components into one measure of cardiovascular health: diet, physical activity, nicotine exposure, sleep duration, body mass index, non-HDL cholesterol, blood glucose and blood pressure. Among 23,003 US adults followed for a median of 7.8 years, estimated life expectancy at age 50 was 27.3 years with a low score, 32.9 years with a moderate score and 36.2 years with a high score. About 42.6% of the gain from a high score was attributed to fewer cardiovascular deaths, and the rest to fewer deaths from other causes. The association was significant in White and Black participants but not in Mexican American participants [3].

Blood pressure and cholesterol act together over a lifetime. Among 438,952 UK Biobank participants, those with gene variants giving both lower LDL cholesterol and lower systolic blood pressure had an odds ratio of 0.61 for major coronary events. Extrapolated to a combined lifelong difference of 38.67 mg/dL of LDL cholesterol and 10 mm Hg of systolic pressure, the odds ratio was 0.22 for major coronary events and 0.32 for cardiovascular death [4]. The individual factors are described under blood pressure, cholesterol, smoking, metabolic health and type 2 diabetes and body weight.

Full deep dive: heart health.

Cardiorespiratory fitness (the capacity of the heart, lungs and muscles to supply and use oxygen during sustained exercise, measured as VO2 max or in METs) is among the strongest predictors of cardiovascular and all-cause mortality. Among 122,007 patients who had a treadmill test at a US medical centre, followed for a median of 8.4 years, elite performers had 80% lower mortality than the least fit quarter (hazard ratio 0.20). Below-average fitness carried a hazard ratio of 1.41 compared with above-average fitness, equal to that of smoking (1.41) and similar to diabetes (1.40) and coronary artery disease (1.29) in the same patients, and no upper limit of benefit was seen [10]. Among 750,302 US veterans, being unfit carried a greater risk than any of the cardiac risk factors examined [6].

Everyday movement is associated with lower risk as well. In a 2025 pooled analysis of step-count studies, 7,000 steps a day compared with 2,000 was associated with 47% lower all-cause mortality, 25% lower incidence of cardiovascular disease and 47% lower cardiovascular mortality, the last graded as low-certainty evidence [11]. Muscle-strengthening activity was associated with 10 to 17% lower all-cause mortality and cardiovascular disease, independent of aerobic activity, with the largest reduction at about 30 to 60 minutes a week [12]. In more than one million adults, about 60 to 75 minutes a day of moderate activity appeared to remove the higher mortality associated with sitting more than eight hours a day [13]. These subjects are covered under exercise and longevity, walking and daily steps, resistance training and sedentary time.

Resting heart rate falls as fitness improves and is used as a marker of cardiovascular risk. In a pooled analysis of 46 studies with 1.25 million participants, each 10 beats per minute higher resting heart rate was associated with a relative risk of 1.09 for all-cause mortality and 1.08 for cardiovascular mortality [14]. A larger review of 87 studies reported a relative risk of 1.17 for all-cause mortality and 1.15 for cardiovascular disease per 10 beats per minute [15].

The PREDIMED trial in Spain assigned 7,447 adults aged 55 to 80 at high cardiovascular risk to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet with advice to reduce fat. After a median of 4.8 years, the hazard ratio for heart attack, stroke or cardiovascular death was 0.69 with olive oil and 0.72 with nuts compared with the control diet. The original 2013 report was withdrawn after protocol deviations in randomisation were found, and the 2018 reanalysis, which did not rely on all participants having been randomly assigned, gave similar results [16]. Eating patterns are described under dietary patterns.

Smoking is one of the largest single causes of cardiovascular death. In a US survey linked to death records covering 202,248 adults, current smokers aged 25 to 79 died at about three times the rate of never-smokers, mostly from cancer, vascular and respiratory disease, and lost more than 10 years of life expectancy. Stopping at ages 25 to 34, 35 to 44 or 45 to 54 gained about 10, 9 and 6 years of life respectively, compared with continuing [17]. A 2024 review of the cardiovascular effects of smoking found that many harms are reduced or reversed after quitting, within a period short relative to the length of smoking history [18]. See smoking.

Most evidence on individual risk factors is observational. Differences in fitness, diet or activity between people are linked with income, education, genetics and undiagnosed illness, and statistical adjustment removes only the part of this that is measured. The step-count and resting heart rate analyses both reported substantial differences between studies, and residual confounding (bias from factors not accounted for) was named as a limitation [11, 14].

Genetic studies avoid some of these biases, but their authors note that lifelong genetic differences in LDL cholesterol and blood pressure cannot be assumed to show the size of benefit achievable by treating the same factors later in life [4]. INTERHEART was a case-control study, which measures exposures after the heart attack has occurred [2], and the Life's Essential 8 findings did not reach significance in every ethnic group [3].

Randomised trials give firmer evidence for specific treatments but carry their own limits. SPRINT excluded people with diabetes, and its intensive-treatment group had more serious episodes of low blood pressure, fainting, electrolyte disturbances and acute kidney injury [5]. PREDIMED had irregularities in randomisation at some sites [16].