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Coronary artery disease and myocardial infarction in young people

Coronary artery disease and myocardial infarction in young people
Literature review current through: Jan 2024.
This topic last updated: Nov 03, 2022.

INTRODUCTION — Although coronary artery disease (CAD) primarily occurs in patients over the age of 40, younger people can be affected. Most studies have used an age cut-off of 40 to 45 years to define "young" patients with CAD or acute myocardial infarction (MI). The same age definition will be used in this review.

Although CAD is an uncommon entity in young patients, it constitutes an important problem for the patient and the treating physician because of the devastating effect of this disease on the more active lifestyle of young patients. In addition, these patients have different risk factor profiles, clinical presentations, and prognoses than older patients. All of these factors should be taken into consideration when treating young patients with CAD.

A separate issue, acute MI during pregnancy, is discussed elsewhere. (See "Acute myocardial infarction and pregnancy".)

EPIDEMIOLOGY — The prevalence of CAD in younger people is difficult to establish accurately since it is frequently a silent process. The frequency with which this occurs was examined in an autopsy study of 760 young (age 15 to 34 years) victims of accidents, suicides, or homicides [1]. Advanced coronary atheromata were seen in 2 percent of males and none were found in females aged 15 to 19. An advanced lesion was present in 20 and 8 percent of people aged 30 to 34, respectively, while 19 and 8 percent, respectively, had a ≥40 percent stenosis of the left anterior descending artery.

There are also limited data on the frequency of MI in younger subjects. In the Framingham Heart Study, the incidence of an MI over a 10-year follow-up was 12.9/1000 in males 30 to 34 years old and 5.2/1000 in females 35 to 44 years old [2]. The incidence of MI was eight to nine times greater in people aged 55 to 64 years. In other studies, 4 to 10 percent of patients with MI were ≤40 or 45 years of age [3-5]. In two series of patients with CAD at ≤40 years of age, females comprised 5.6 and 11.4 percent of patients [3,6].

CORONARY RISK FACTORS — The relative importance of risk factors for the development of CAD according to age was evaluated in a report in which 11,016 males aged 18 to 39 years were followed for 20 years [7]. The relative risks associated with the traditional risk factors were of similar magnitude as in a group of 8955 males aged 40 to 59 years. These included:

Age – Relative risk 1.63 per six-year increase

Serum cholesterol – Relative risk 1.92 per 40 mg/dL [1.04 mmol/L] increase

Systolic blood pressure – Relative risk 1.32 per 20 mmHg increase

Cigarette smoking Relative risk 1.36 per 10 cigarette/day increase

Young patients with MI usually have multiple risk factors for CAD. In some studies, for example, as many as 90 to 97 percent had one or more traditional risk factors for atherosclerosis [8-10]. In a prospective study of over 7000 females with an average age of 27 years at baseline who were followed for an average of 31 years, there were 47 CAD deaths [11]. The CAD mortality rates for those with no risk factors, only one risk factor, or two or more risk factors were 0.7, 2.4, and 5.4 per 1000 person-years, respectively. A comparable relationship was seen for cardiovascular disease mortality and for all-cause mortality. (See "Overview of established risk factors for cardiovascular disease".)

Smoking — Cigarette smoking is the most common and most modifiable risk factor in young patients. It has been noted in 65 to 92 percent of young patients with MI, compared to 24 to 56 percent of patients older than 45 years of age [6,9,12-16]. (See "Cardiovascular risk of smoking and benefits of smoking cessation".)

In a registry study that enrolled 6892 patients with acute ST-elevation MI treated by primary percutaneous coronary intervention from 1998 to 2010, smoking rates were highest for those aged 18 to 34 years, at 78 percent, compared with a smoking rate of 24 percent in that age stratum of the general population, with smoking rates notably decreasing with increasing age in the STEMI population [17].

Family history — Younger patients with CAD more often have a family history of premature CAD: 41 compared to 28 and 12 percent in middle aged or older patients, respectively [9]; and 57 versus 43 percent in two series [12]. A higher incidence of a positive family history in young patients (64 percent) was noted in the largest report of 823 patients [6].

In addition, the offspring of patients with premature CAD are more likely to have coronary risk factors than those without such a family history [18]. These include excess body weight and higher levels of serum cholesterol, glucose, and insulin. These offspring are also more likely to have evidence of vascular disease such as endothelial dysfunction and increased carotid artery intima-media thickness [19].

The association between family history and premature CAD can be due to both genetic and environmental factors. This was addressed in a study of 398 families in which 62 vascular biology genes were evaluated [20]. Missense variants of several thrombospondin genes were significantly associated with MI and CAD.

Lipid abnormalities — Hypercholesterolemia is common in young patients with CAD, but its prevalence is similar to that in older patients. However, when compared to older patients, young patients have lower mean serum high density lipoprotein (HDL) concentrations (35 versus 43 mg/dL [0.9 versus 1.1 mmol/L]) and higher serum triglycerides (239 versus 186 mg/dL [2.7 versus 2.1 mmol/L]) [15]. (See "HDL cholesterol: Clinical aspects of abnormal values".)

Hypertriglyceridemia was, in one series, the most common lipid abnormality in young patients with MI [21]. It may be associated with glucose intolerance and a predominance of small atherogenic LDL particles, both of which predispose to atherosclerosis. (See "Hypertriglyceridemia in adults: Management".)

Diabetes and hypertension — Two other important coronary risk factors, diabetes mellitus and hypertension, appear to be less common in young patients with CAD than in older patients [6,12]. However, young patients frequently have subtle problems with glucose metabolism. In one study of 108 patients without a history of diabetes mellitus who had an MI before the age of 45, 65 percent had decreased oral glucose tolerance and a hyperinsulinemic response to oral glucose challenge [21]. This finding is consistent with other observations that impaired glucose tolerance in the absence of overt diabetes is a risk factor for coronary disease. (See "Prevalence of and risk factors for coronary heart disease in patients with diabetes mellitus", section on 'CHD before diabetes'.)

Obesity — Obesity appears to be an independent risk factor for coronary atherosclerosis, at least in young males. This was illustrated in an autopsy study of approximately 3000 persons between the ages of 15 and 34 who died from noncardiac causes [22]. Increasing body mass index was associated with both fatty streaks and raised atherosclerotic lesions in the right coronary and left anterior descending coronary arteries in young men, but not young females. The effect of obesity on other risk factors (eg, lipid abnormalities, hypertension, glucose intolerance) accounted for only about 15 percent of the relationship between obesity and coronary atherosclerosis.

How this might occur is not known, but other studies have noted an apparently independent effect of obesity as an important coronary risk factor. A report from the Framingham Heart Study suggested that obesity in middle-aged subjects could account for as much as 23 percent of cases of CAD in males and 15 percent in females [23]. (See "Overweight and obesity in adults: Health consequences".)

Paradoxical embolism — Paradoxical embolism, primarily through a patent foramen ovale, is a rare cause of myocardial infarction in younger patients [24,25]. (See "Patent foramen ovale".)

Other factors — A variety of other possible contributing factors have been identified in young patients with MI. These include:

Oral contraceptive use in young females, primarily when combined with heavy smoking [26]. (See "Combined estrogen-progestin contraception: Side effects and health concerns".)

Frequent cocaine use, which, in the Third National Health and Nutrition Examination Survey of 10,085 adults between the ages of 18 and 45, accounted for 25 percent of nonfatal MIs [27]. (See "Clinical manifestations, diagnosis, and management of the cardiovascular complications of cocaine abuse", section on 'Myocardial ischemia/infarction'.)

Smoking marijuana may be a rare trigger of MI [28]. (See "Cannabis use disorder: Clinical features, screening, diagnosis, and treatment".)

Factor V Leiden, which is inactivated less efficiently by activated protein C than wild-type factor V, leads to a procoagulant state by increasing thrombin generation. In a report of 107 patients with premature MI but no significant coronary artery stenosis (average age 44), the prevalence of carriers for factor V Leiden was significantly higher in these patients compared to 244 with an MI and significant stenoses and 400 healthy controls (12 versus 4.5 and 5 percent) [29]. At least in young females, the increase in risk with factor V Leiden may be confined to smokers [30]. (See "Factor V Leiden and activated protein C resistance".)

Psychosocial factors, such as anger, may be important in the development of premature CAD [31]. (See "Psychosocial factors in coronary and cerebral vascular disease".)

In females, acute MI may be more common during the follicular phase of the menstrual cycle, a time of relative hypoestrogenemia [32,33]. (See "Normal menstrual cycle".)

Risk factors in childhood — A separate issue is the influence of cardiovascular risk factors in childhood on the development of CAD in later life. The limited data supporting such a correlation are discussed elsewhere. (See "Overview of established risk factors for cardiovascular disease", section on 'Risk factors in childhood'.)

Children who develop Kawasaki disease (KD) in childhood (usually before the age of five) are at risk of developing coronary artery aneurysms and stenoses. (See 'Kawasaki disease' below.) It is not known whether KD is a risk factor for the development of atherosclerotic coronary disease, although intimal abnormalities have been found in sites remote from the coronary aneurysms in some patients [34,35].

CLINICAL MANIFESTATIONS — The clinical presentation of CAD in younger patients is different from that in older patients. A higher proportion of young patients do not experience angina [4], and, in the majority of cases, an acute coronary syndrome that progresses rapidly to MI (most often an ST elevation MI) if left untreated is the first manifestation of CAD [3,15,36]. These relationships were illustrated in a series of 200 patients with CAD documented by angiography [15]. Patients ≤45 years of age had a lower prevalence of stable angina than patients ≥60 years of age (24 versus 51 percent) and a higher incidence of acute coronary syndromes (76 versus 49 percent). A greater likelihood of complex lesions on arteriography may have contributed to the development of an acute coronary syndrome. (See "Mechanisms of acute coronary syndromes related to atherosclerosis".)

Similar findings were noted in another report of 85 patients less than 40 years of age who were referred for cardiac catheterization and angiography [36]. The first manifestation of CAD was angina in 14 percent and acute MI in 69 percent, two-thirds of whom denied chest pain prior to the infarct. Among those who have preceding chest pain, the first episodes often occur only in the week prior to MI [3].

Establishing the diagnosis of an acute MI in young patients is identical to the diagnosis in other patients and is discussed separately. (See "Diagnosis of acute myocardial infarction".)

ANGIOGRAPHIC FINDINGS — In the majority of patients younger than 45 years of age, angiographic studies were performed because of a history of MI. As expected, major differences were found when compared to older patients.

Coronary disease severity — Younger patients have a higher incidence of normal coronary arteries, mild luminal irregularities, and single vessel coronary artery disease than do older patients [10,12,13,15,37].

One of the largest reports of angiographic findings in young patients with CAD comes from a substudy of the CASS trial, which compared the results of coronary angiography in 504 young males (≤35 years of age) and females (≤45 years of age) with a history of an MI to those in over 8300 older patients [12]. The following significant differences were noted:

Normal coronary arteries were more common in the young patients (18 versus 3 percent). Young females had a higher frequency of angiographically normal coronary arteries than young males, despite a 10 year age difference in the definition of "young."

Single vessel coronary disease was more common (38 versus 24 percent) and three vessel disease was less common (14 versus 39 percent) in the younger patients.

Although some series have shown a predilection for involvement of the left anterior descending artery in young patients [13,37], this was not found in the CASS substudy.

In another large series of 823 young patients with CAD, single vessel disease was present in 55 to 60 percent [6].

Spontaneous coronary dissection — Spontaneous coronary artery dissection is a rare cause of acute MI that is more common in younger patients (under age 50) and in females. In females, the risk of spontaneous coronary dissection appears to be increased during the peripartum period. This disorder is discussed in detail separately. (See "Clinical features and diagnosis of coronary heart disease in women", section on 'Role of coronary angiography'.)

Kawasaki disease — Kawasaki disease (KD) is a vasculitis of infancy and early childhood. It typically presents as an acute febrile illness in children under the age of five; the incidence is higher in Asian and Asian-American populations than in other groups [38]. The etiology of KD is unknown, although an inflammatory response precipitated by an infectious agent is suggested by some epidemiologic data. (See "Kawasaki disease: Epidemiology and etiology".)

The most important complication of KD is coronary vasculitis, leading to coronary aneurysm formation in 20 to 25 percent of untreated patients during the acute stage of the disease. Nearly half of acute aneurysms regress, but approximately 20 percent lead to the development of coronary stenosis in the long term. Patients can present with MI or SCD. (See "Cardiovascular sequelae of Kawasaki disease: Clinical features and evaluation".)

While patients with known KD are followed for the development of coronary artery stenoses, some patients who were not previously diagnosed are recognized only after presenting with sequelae of CAD, including MI, heart failure, and SCD [39,40]. Thus, young patients with MI should be asked about a possible childhood history of KD.

Normal coronary arteries — The prevalence of significant coronary disease is lower in females presenting with chest pain than in males [41,42]. This was illustrated in a report of 886 patients referred for angiographic evaluation of presumed angina, 23 percent of whom were females [41]. Normal coronary arteries were much more common in females (41 versus 8 percent in males). Myocardial ischemia is present in a minority of the females with normal coronary arteries (20 percent in two reports), perhaps due to microvascular disease [43,44]. (See "Microvascular angina: Angina pectoris with normal coronary arteries".)

MANAGEMENT OF ACUTE MI — Management of young patients with acute MI is similar to older patients with MI. The overall approach to therapy is not dependent on age and is discussed elsewhere. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes".)

PROGNOSIS AFTER MI — MI occurring at an early age raises the potential of a malignant atherosclerotic diathesis and an adverse prognosis. However, as noted above, many such patients do not have severe coronary disease [12,45], and most series have noted both a favorable short- and long-term prognosis in such patients.

In-hospital mortality — The in-hospital mortality in young patients has ranged from 0 to 4 percent, a value lower than that in older patients [3,9,46,47]. This was illustrated in a review of 2643 patients with an acute MI: the in-hospital mortality for those aged ≤45 years, 46 to 70 years, and >70 years was 2.5, 9, and 21 percent, respectively [9]. Virtually identical rates were noted in a review from the GISSI-2 database of patients with an ST elevation MI treated with thrombolytic therapy [46].

Long-term outcome — Young patients also have a good long-term outcome after MI [6,12,48]. In the large CASS trial substudy mentioned above, survival rates at seven years after an MI were 84 versus 75 percent for young and older males and 90 versus 77 percent for young and older females [12]. The cause of death was cardiovascular in 84 percent of patients, a finding that was not affected by age or sex. After adjusting for more favorable baseline characteristics in younger patients, there was no difference in the rate of reinfarction between younger and older males (18 versus 20 percent) or younger and older females (15 versus 21 percent).

Longer-term data were provided by a second study of 823 patients with CAD, 55 percent of whom had a prior MI and 10 percent of whom had diabetes [6]. Mortality at 15 years was 30 percent overall, but markedly increased in those with prior MI (45 percent), diabetes (65 percent), and left ventricular ejection fraction less than 30 percent (83 percent). The number of diseased vessels in this and another report [48] was not predictive of outcome, because patients with more severe disease were more likely to undergo revascularization. In the latter study, 17-year mortality was only 9 percent in patients with normal coronary arteries [48].

In addition to the mortality risk, recurrent coronary events are not uncommon. This was illustrated in a report of 108 nondiabetic males ≤45 years of age followed for six to nine years after an acute MI; the event rate (death, acute MI, coronary revascularization) of 50 percent [21].

In multivariable models, predictors of long-term mortality or reinfarction in addition to prior MI, diabetes, and low ejection fraction have included atrial fibrillation, use of antiarrhythmic drugs, continued smoking, and the plasma PAI-1 concentration [6,9,21].

The issue of whether there are differences in prognosis between the young females and males within the first year after MI was evaluated in an observational study of 3501 patients 18 to 55 years of age [49]. Health status, as measured using health status instruments (eg, the Seattle Angina Questionnaire), was assessed at baseline and 1 and 12 months after MI. At all time points, females had worse health status outcomes than males of a similar age.

MANAGEMENT OF CHRONIC CAD — The management of stable angina, including the indications for revascularization, is similar in younger and older patients. Routine coronary angiography is not recommended in young patients who have stable CAD. However, when indicated, both PCI and CABG are effective and are associated with lower risks in younger compared to older patients. (See "Chronic coronary syndrome: Overview of care" and "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)

Management should also include intensive risk factor reduction including smoking cessation, initiation of an exercise program, aggressive lipid lowering, screening for depression, and, in appropriate patients, treatment of diabetes and hypertension. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Percutaneous intervention — The long-term outcome of young patients undergoing percutaneous coronary intervention (PCI) is quite good [6,50,51]. In a study that assessed the outcome of PCI in 140 consecutive patients ≤40 years of age, the acute success rate was 93 percent with a 28 percent rate of angiographic restenosis [50]. Ten-year overall and event-free survival (without MI, elective CABG, or repeat PCI) following PCI were 96 and 58 percent, respectively. Among survivors, 88 percent were free of angina, 93 percent had returned to work, and 19 percent underwent a repeat revascularization procedure because of disease progression at other sites or restenosis.

A second report compared the outcome of PCI in 89 patients ≤40 years of age with that of 1916 patients over 40 [51]. Procedural success was similar in the young and older patients (90 versus 86 percent); there were no periprocedural complications in the younger group, while 7 percent of patients in the older group had a cardiac event (death, MI, or urgent CABG). After a mean follow-up of 30 months, there were no deaths; however, 5 percent required elective CABG and 34 percent underwent repeat PCI for restenosis or disease progression.

The applicability of these findings on repeat revascularization, published in 1994, to current practice is uncertain. Advances such as coronary artery stenting, particularly drug-eluting stents and more aggressive antiplatelet therapy have reduced the risk of restenosis, while aggressive lipid lowering with statin therapy may reduce the risk of disease progression. (See "Percutaneous coronary intervention with intracoronary stents: Overview" and "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Bypass surgery — Coronary artery bypass grafting (CABG) is easier to perform in young patients because they are usually in better physical condition than older patients and can better tolerate the stress of surgery and general anesthesia. One report reviewed the data on 138 patients less than 40 years of age who underwent CABG with a saphenous vein graft, primarily for angina [52]. More than one-half had a prior MI, 60 percent had three-vessel coronary artery disease, and 42 percent had serious left ventricular dysfunction. There was no operative mortality, and the rate of perioperative transmural acute MI was 4 percent. Survival rates at five and ten years were 95 and 84 percent, respectively. There was no significant difference between the long-term patency rate of the saphenous vein grafts compared with other series that included older age groups.

Similar results were noted in another study of 107 patients ≤35 years of age in whom the actuarial survival at five and ten years was 94 and 85 percent, respectively, and the actuarial event-free survival was 77 and 53 percent, respectively [53]. Survival was decreased by multivessel disease and impaired left ventricular function, and event-free survival was decreased by a family history of coronary disease and cigarette smoking. The long-term patency was much higher with mammary artery grafts (93 versus 56 percent with saphenous vein grafts).

Better long-term patency with arterial grafts has been noted in other studies in young patients [54] and is well described in older patients. Arterial grafts are now preferred in all patients undergoing CABG. (See "Coronary artery bypass graft surgery: Graft choices".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)" and "Society guideline links: ST-elevation myocardial infarction (STEMI)".)

SUMMARY

Epidemiology – Symptomatic coronary artery disease (CAD) is uncommon in young males and females (age less than 40 to 45 years). (See 'Epidemiology' above.)

Risk factors – Similar to older patients, the risk factors for CAD include:

Family history – Younger patients with CAD more often have a family history of premature CAD. (See 'Family history' above.)

Smoking – Cigarette smoking is the most common and most modifiable risk factor in young patients. (See 'Smoking' above.)

Diabetes and hypertension – Diabetes mellitus and hypertension appear to be less common in young patients with CAD than in older patients. (See 'Diabetes and hypertension' above.)

Other risk factors – Other risk factors such as cocaine use, factor V Leiden, and oral contraceptive use are more common in younger individuals with CAD. (See 'Other factors' above.)

Clinical manifestations – The clinical presentation of CAD in younger patients is different from that in older patients. A higher proportion of young patients do not experience angina, and, in the majority of cases, an acute coronary syndrome that progresses rapidly to MI if left untreated is the first manifestation of CAD. (See 'Clinical manifestations' above.)

Angiographic findings – Younger patients have a higher incidence of normal coronary arteries, mild luminal irregularities, and single vessel coronary artery disease than do older patients. Rarer causes of CAD such as spontaneous coronary dissection or Kawasaki disease occur more commonly in the young. (See 'Angiographic findings' above.)

Management – In general, the management of CAD in the young is similar to that in older individuals. (See 'Management of chronic CAD' above.)

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Topic 50 Version 15.0

References

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