Coronary heart disease and myocardial infarction in young men and women

Coronary heart disease and myocardial infarction in young men and women
Emad Eldin Omar
assistant prof. of critical care medicin, cairo university
consultant of international cardiology
member of european society of cardiology
INTRODUCTION — Although coronary heart disease (CHD) primarily occurs in patients over the age of 40, younger men and women can be affected.
The prevalence of CHD in younger subjects 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 . Advanced coronary atheromata were seen in 2 percent of men and no women aged 15 to 19. An advanced lesion was present in 20 and 8 percent of men and women 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 men 30 to 34 years old and 5.2/1000 in women 35 to 44 years old. The incidence of MI was eight to nine times greater in men and women aged 55 to 64 years. In other studies, 4 to 10 percent of patients with MI were ≤40 or 45 years of age. In two series of patients with CHD at ≤40 years of age, women comprised 5.6 and 11.4 percent of patients.
CORONARY RISK FACTORS — The relative importance of risk factors for the development of CHD according to age was evaluated in a report in which 11,016 men aged 18 to 39 years were followed for 20 years. The relative risks associated with the traditional risk factors were of similar magnitude as in a group of 8955 men 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
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.
Family history — Younger patients with CHD more often have a family history of premature CHD: 41 compared to 28 and 12 percent in middle aged or elderly patients, respectively; and 57 versus 43 percent in two series. A higher incidence of a positive family history in young patients (64 percent) was noted in the largest report of 823 patients.
In addition, the offspring of patients with premature CHD are more likely to have coronary risk factors than those without such a family history. 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.
The association between family history and premature CHD 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. Missense variants of several thrombospondin genes were significantly associated with MI and CHD.
Lipid abnormalitites — Hypercholesterolemia is common in young patients with CHD, 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]) .
Hypertriglyceridemia was, in one series, the most common lipid abnormality in young patients with MI. It may be associated with glucose intolerance and a predominance of small atherogenic LDL particles, both of which predispose to atherosclerosis.
Diabetes and hypertension
Two other important coronary risk factors, diabetes mellitus and hypertension, appear to be less common in young patients with CHD than in older patients. However, young patients frequently have subtle problems with glucose metabolism.
Obesity — Obesity appears to be an independent risk factor for coronary atherosclerosis, at least in young men. This was illustrated in an autopsy study of approximately 3000 persons between the ages of 15 and 34 who died from noncardiac causes. 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 women. 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.
Paradoxical embolism
Paradoxical embolism, primarily through a patent foramen ovale, is a rare of myocardial infarction in younger patients.
Other factors — A variety oother possible contributing factors have been identified in young patients with MI. These include:
Oral contraceptive use in young women, primarily when combined with heavy smoking.
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.
Smoking marijuana may be a rare trigger of MI.
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) . At least in young women, the increase in risk with factor V Leiden may be confined to smokers.
Psychosocial factors, such as anger, may be important in the development of premature CHD.
In women, acute MI may be more common during the follicular phase of the menstrual cycle, a time of relative hypoestrogenemia.
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. 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.
CLINICAL PRESENTATION
The clinical presentation of CHD 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 (most often an ST elevation MI) if left untreated is the first manifestation of CHD.
Establishing the diagnosis of an acute MI is based upon the typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) in biochemical markers of myocardial necrosis with at least one of the following: ischemic symptoms; development of pathologic Q waves on the electrocardiogram (ECG); or ECG changes indicative of ischemia (ST segment elevation or depression).
A potential diagnostic problem that is most common in younger subjects is that myocarditis can mimic an acute MI. This disorder should be particularly considered
in young patients with a clinical presentation of an acute coronary syndrome who have a normal coronary angiogram.
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 .
One of the largest reports of angiographic findings in young patients with CHD comes from a substudy of the CASS trial, which compared the results of coronary angiography in 504 young men (≤35 years of age) and women (≤45 years of age) with a history of an MI to those in over 8300 older patients . The following significant differences were noted:
Normal coronary arteries were more common in the young patients (18 versus 3 percent). Young women had a higher frequency of angiographically normal coronary arteries than young men, 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, this was not found in the CASS substudy.
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 women. In women, the risk of spontaneous coronary dissection appears to be increased during the peripartum period. This disorder is discussed in detail separately.
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. The etiology of KD is unknown, although an inflammatory response precipitated by an infectious agent is suggested by some epidemiologic data.
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.
Normal coronary arteries — The prevalence of significant coronary disease is lower in women presenting with chest pain than in men. This was illustrated in a report of 886 patients referred for angiographic evaluation of presumed angina, 23 percent of whom were women. Normal coronary arteries were much more common in women (41 versus 8 percent in men).
MANAGEMENT OF ACUTE MI ST elevation MI — Young patients with an acute ST elevation MI should be treated with primary PCI or, if not available, thrombolytic therapy. Prospective randomized trials assessing primary PCI and thrombolytic therapy for an acute
ST elevation MI have observed that both young and old patients have a better outcome with PCI than thrombolysis. However, young patients do better than older patients regardless of the therapy received. In the GUSTO-IIb trial, for example, the outcome was improved with PCI compared with thrombolytic therapy for each 10-year patient group. Irrespective of treatment, the risk increased with age; after adjusting for baseline characteristics, each increment of 10 years of age increased the risk of death or reinfarction by 1.32.
Although data are limited, young patients also appear to respond well to thrombolytic therapy. In one study, for example, the clinical response to streptokinase, as measured by TIMI II or III flow in the infarct-related artery, was similar in patients ≤35 and ≥55 years of age (74 versus 73 percent) .
Non-ST elevation ACS
Patients with a non-ST elevation acute coronary syndrome (non-ST elevation (non-Q wave) MI or unstable angina) are first stabilized with medical therapy and should undergo early coronary angiography and revascularization, if appropriate.
The efficacy of this early invasive strategy in patients under age 40 is uncertain since few such patients were included in the large clinical trials. Many cardiologists feel obligated to refer these patients for
coronary angiography given their “young age” and the “need to know the coronary anatomy.” However, the observation that some young patients have normal coronary arteries (18 percent in the CASS trial) or nonobstructive coronary disease does not justify the routine use of this approach. An exercise stress test is a simpler and more cost-effective modality to risk stratify young patients with CHD and an MI.
The efficacy of this approach is illustrated by the following observations. One report evaluated 129 patients under 40 years of age who had coronary angiography within 60 days of their first acute MI. Patients without evidence of spontaneous or induced ischemia were compared to those who had ischemia or abnormal stress test after the MI; the two groups were similar with regard to all clinical variables.
In the patients without evidence of ischemia, the coronary arteries were normal in 23 percent, single or multivessel disease was present in 60 and 16 percent, respectively, and no patient had left main disease. None of these patients underwent PCI or CABG and, after a 77 month follow-up, the cardiac mortality was 5 percent.
The patients with documented ischemia were more likely to have extensive CHD (36 percent had multivessel disease, and 4 percent had left main disease) and less likely to have no or one-vessel disease (11 and 49 percent, respectively). The revascularization rate in this group was 41 percent.
PROGNOSIS AFTER MI
Myocardial infarction occurring at an early age raises the disturbing potential of a malignant atherosclerotic diathesis and an adverse prognosis. However, as noted above, many such patients do not have severe coronary disease 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.
Long-term outcome — Young patients also have a good long-term outcome after MI. 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 men and 90 versus 77 percent for young and older women. The cause of death was cardiovascular in 84 percent of patients, a finding that was not affected by age or gender. After adjusting for more favorable baseline characteristics in younger patients, there was no difference in the rate of reinfarction between younger and older men (18 versus 20 percent) or younger and older women (15 versus 21 percent).
In addition to the mortality risk, recurrent coronary events are not uncommon. This was illustrated in a report of 108 nondiabetic men ≤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.
In multivariate 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 .
MANAGEMENT OF CHRONIC CHD — 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 CHD. However, when indicated, both PCI and CABG are effective and are associated with lower risks in younger compared to older patients.
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.
Percutaneous intervention
The long-term outcome of young patients undergoing percutaneous coronary intervention (PCI) is quite good. 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. 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. 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.
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. 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. 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 and is well described in older patients. Arterial grafts are now preferred in all patients undergoing CABG.