(Circulation. 1996;94:3138-3145.)
© 1996 American Heart Association, Inc.
Articles |
Effect of Hypertension and Cardiac Hypertrophy on Coronary Artery Morphology in Sudden Cardiac Death
the Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC.
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Abstract |
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Background Epidemiological studies have shown that hypertension and left ventricular hypertrophy (LVH) increase the risk of sudden cardiac death (SCD) in patients with severe coronary artery disease (CAD). However, autopsy studies comparing the morphological substrates for SCD in normotensives and hypertensives are lacking.
Methods and Results Heart weight and coronary plaque morphology were prospectively compared in SCD in 36 hypertensive and 63 normotensive individuals. The frequency of CAD was similar in hypertensives (69%, n=25) and normotensives (73%, n=46). In 71 hearts with CAD, acute coronary thrombi were present in 76% of normotensives versus 36% of hypertensives (P=.002), LVH was present in 64% of hypertensives versus 33% of normotensives (P=.01) and in 72% of hypertensives with one-vessel disease versus 17% of normotensives with one-vessel disease (P=.0005), and a healed or acute infarct without acute thrombus was present in 36% of hypertensives versus 9% of normotensives (P=.007). Heart weight was higher in all cases of plaque rupture (519±109 g) than eroded plaque (381±92 g, P=.0002). In contrast to hypertensives, normotensive hearts with severe CAD showed a stepwise increase in heart weight with one-, two-, and three-vessel disease (P=.01).
Conclusions Severe CAD is present in most SCD in hypertensive and normotensive individuals, but acute thrombi are more common in normotensives. LVH is an important contributing mechanism of SCD in hypertensives, especially in cases of one-vessel disease. LVH is associated with plaque rupture and extent of disease in SCD in normotensives with severe CAD.
Key Words: hypertension • death, sudden • hypertrophy • coronary disease
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Introduction |
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The frequency of coronary thrombosis in SCD secondary to atherosclerosis varies from 20% to 70%.1 This large range is primarily due to the population studied. The time interval between onset of symptoms and death, the presence of acute myocardial infarction, and the type of prodromal symptom (stable angina, unstable angina, or no apparent symptoms) all affect the incidence of thrombi in SCD.2 3 4
Systemic hypertension increases the risk for acute coronary events in patients with CAD.5 6 7 SCD in patients with coexistent hypertension and CAD probably involves mechanisms other than coronary thrombosis.5 In hypertensive patients, both LVH and CAD are independent predictors of ventricular arrhythmias.8 LVH, as diagnosed by ECG, has an adverse impact on survival in patients with and without coronary disease.9 Antihypertensive treatment with ß-blockers or calcium channel blockers may be more effective in reducing SCD in hypertensives than diuretics alone, which do not decrease LV mass.10 11 12 13
The goals of the present study were to define the pathological findings in a prospective series of SCD in patients with and without hypertension. The major focus of this study was to define the pathological substrates of SCD, comparing ratios of heart weight to body mass, LV wall thickness, extent of epicardial disease, substrates for thrombosis, and incidence of thrombosis between hypertensives and normotensives. These data may increase our understanding of the morphological substrates for SCD in patients with systemic hypertension.
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Methods |
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Selection of Cases for Hypertension Evaluation
One hundred eighteen cases of sudden unexplained death were reviewed in consultation at the Office of the Chief Medical Examiner, State of Maryland, including examination of hearts and bilateral kidney sections. Cases of ruptured acute myocardial infarction were excluded at the time of autopsy. Investigators' reports were reviewed for a history of hypertension, medication usage, cigarette smoking, diabetes, and previous cardiovascular illness. Cases were separated into known cases of hypertension, cases in which a physician related an absence of hypertension, and cases in which a previous medical history was unknown or inconclusive.
Selection of SCD Cases and Definition of Severe Coronary Disease
After subsequent review of results of full autopsy and toxicological reports, 10 cases from the original 118 were excluded because of noncardiac causes of death; an additional 9 were excluded because of inconclusive determination of hypertension (see below). Therefore, a total of 99 SCDs with determination of hypertensive status remained for study. SCD was defined as witnessed sudden unexpected death within 6 hours of the onset of symptoms from a stable medical condition or death of an individual who had been seen in stable condition <24 hours antemortem after exclusion of any other potentially lethal noncardiac or toxicological cause of death. Coronary artery findings in 56 of the hearts in this study were previously reported in the absence of data concerning hypertension history or kidney morphology.1
Of the 99 cases of SCD, 71 had severe coronary disease (one or more epicardial arteries narrowed by 
75% in cross-sectional luminal area). Although critical narrowing of one coronary artery is an incidental finding at autopsy in up to 10% of adult males,14 75% to 80% cross-sectional luminal narrowing is typically used as a critical cutoff point at which coronary vascular dilatory reserve is exhausted,15 and it corresponds to critical stenosis as defined at angiography.
Tissue Handling and Processing
In conjunction with the forensic pathologist, all hearts were examined fresh and uncut. Coronary artery perfusion fixation was performed on the day of autopsy. Hearts were dissected as previously described.1 Coronary arteries were perfusion-fixed at physiological pressures (100 mm Hg) with buffered formalin and studied by postmortem angiography. Epicardial arteries were cut transversely at 2- to 3-mm intervals and decalcified before sectioning if necessary. Sections were submitted for histological examination if arteries demonstrated 50% cross-sectional luminal narrowing by gross examination.
Definitions and Measurements
The presence of acute and healed myocardial infarction was determined as previously described.1 Atherosclerotic CAD denoted one or more major coronary arteries with luminal thrombus or narrowing by plaque of 75% in cross-sectional area. Heart weight was recorded to the nearest gram before fixation after removal of all but 4 cm of pulmonary trunk and ascending aorta above the semilunar valves on a Sartorius digital scale. Heart weight was expressed both in grams and as a ratio of heart weight to body weight. LV thickness was measured at the level of the papillary muscles, excluding the papillary muscle itself, in four quadrants: septum and anterior, lateral, and posterior walls. The mean dimension was tabulated, excluding areas with gross infarcts. Cardiac hypertrophy was considered present if heart weight exceeded the 95% CIs of population-based tables based on sex, age, and body weight.16
Evaluation of Kidney Sections and Determination of Hypertensive Status
One section of each kidney was sectioned at 4 µm and stained for elastin by the Movat pentachrome method. Arterial thickening was measured with an ocular reticule as previously described.17 18 Approximately 20 arteries 150 to 500 µm in diameter were analyzed from each kidney, and the kidney changes were scored as 1, arteries and arterioles essentially free of intimal thickening; 2, focal mild intimal thickening; 3, concentric intimal thickening less than or equal to the thickness of the media; 4, concentric intimal thickening greater than the thickness of the media without concentric elastic duplication; and 5, concentric intimal thickening greater than the thickness of the media with concentric elastic duplication in 3 or more vessels examined.15
The mean arterial score was assessed without knowledge of the history for all 118 hearts initially studied. In patients with a known history, a score of 3 had a positive predictive value of 60%, and a score of 
2 had a negative predictive value of 93%. Because of the relatively poor positive predictive value, a proportionately large number of normotensives would be misclassified as hypertensive, given the low prevalence (33%) of hypertensives in the group with a medical history. Among cases with a known history, excluding a score of 3, a score of 4 was a 93% predictor of hypertension (positive predictive value), and a score of 2 remained 93% (negative predictive value). Therefore, to minimize false assignment of hypertension in cases without history, those cases with a kidney score of 3 were excluded from the study in the absence of history, resulting in the exclusion of nine cases.
Histological Classification of Coronary Plaques
Coronary plaques were classified on the basis of the "culprit plaque," which was defined as the area of greatest luminal narrowing or area of acute thrombosis. All active coronary lesions (those with thrombi) and the most severely narrowed inactive coronary lesions from each major coronary artery were magnified and digitized. The following computerized morphometric measurements were performed on histological sections (IPLab image analysis software, version 2.5): arterial size (defined by the area within the internal elastic lamina), lumen area, and percent arterial stenosis [100x(1-lumen area/arterial size)]. In cases of thrombi, luminal narrowing was measured excluding area of fibrin, red cells, and platelet thrombus.
Active plaques were classified as eroded plaque (Fig 1
, without plaque rupture or connection of luminal thrombus with necrotic core) and ruptured plaque (Fig 2, with connection of necrotic core and artery lumen). Thrombi in active plaques were characterized as nonocclusive or occlusive. To establish an absence of connection of luminal thrombus with necrotic core and to establish the presence of luminal thrombus in cases of ruptured plaque, serial sections were sometimes required. Segments that demonstrated luminal thrombus but no rupture into a lipid core underwent serial step-sectioning and staining at every 40 µm for at least 1 to 2 cm to determine whether rupture of a fibrous cap was present deeper in the section. In the absence of active plaques, culprit plaques represented the stable plaque with the greatest degree of narrowing 75% of the cross-sectional lumen as determined by morphometry. The degree of calcification in the culprit plaque was graded as 0 to 4+, corresponding to the numbers of quadrants of plaque with calcification present histologically.
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75% cross-sectional luminal narrowing of vessel diameter. Multiple levels failed to demonstrate connection with necrotic core. Section was taken from mid left anterior descending coronary artery of a 46-year-old man with no history of hypertension and normal kidneys; heart weight was 365 g. Movat pentachrome, magnification x30. B, Higher magnification of eroded plaque. Superficial disruption of plaque with organizing thrombus at base and fibrin-platelet thrombus projecting into lumen (hematoxylin-eosin, x90).
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Statistical Analysis
Numerical data are presented as mean±SD. Categorical variables were compared by Fisher's exact test or 
2 test, and continuous variables by Student's t test for unpaired data. For determination of independent effect of variables on plaque morphology, logistic regression was used.
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Results |
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Causes of SCD
In 25 of 36 hypertensives (69%), there was severe CAD (
75% cross-sectional luminal narrowing of one or more epicardial arteries). Other causes of death in hypertensives were concentric LVH (n=6, 17%), dilated cardiomyopathy (n=2, 6%), hypertrophic cardiomyopathy (n=1, 3%), and cardiac arrhythmia with no gross or microscopic abnormalities (n=2, 6%). Causes of death in normotensives were severe CAD (n=46, 73%), dilated cardiomyopathy (n=5, 8%), idiopathic LV scarring (n=2, 3%), rheumatic valve disease (n=2, 3%), myocarditis (n=2, 3%), right ventricular dysplasia (n=1, 2%), hypertrophic cardiomyopathy (n=1, 2%), and coronary artery dissection (n=1, 2%); in 5 cases (8%), the cause of death was presumed cardiac arrhythmias in the absence of structural or microscopic abnormalities. There was a weakly significant correlation between heart weight and hypertension (R2=.059, P=.03). There was a stronger correlation between heart weight and hypertension when body weight was considered (R2=.17, P=.0005).
SCD With Severe Coronary Disease: Age, Race, Hypertensive History, and Circumstances of Arrest
The mean age of these 71 subjects was 50.4±10.4 years; there were 57 men and 14 women, 50 whites and 21 blacks. A positive history of hypertension or a kidney score of 4 was present in 25 subjects (hypertensive group); the remaining 46 subjects were considered normotensive. The mean age of hypertensives was greater than that of normotensives (P=.001) (Table 1).
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Of the 25 hypertensives, 14 had a history of hypertension, and 11 were diagnosed on the basis of kidney scores 4. Of the 14 with a history, 3 refused medications, and in 2 the specific medications were not known; remaining drug histories included clonidine (n=2), diuretics (n=2), ß-blockers (n=3), and captopril (n=2). In addition to hypertension, known medical conditions in the hypertensive group included previous myocardial infarction (n=2), diabetes mellitus (n=3), cerebrovascular accident (n=1), ethanol abuse (n=3), and carcinoma of the prostate (n=1). Known medical conditions in the 46 normotensives included drug abuse (n=3), ethanol abuse (n=4), seizure disorder (n=1), atherosclerotic heart disease (n=2), duodenal ulcer (n=1), schizophrenia (n=1), and diabetes mellitus (n=2).
There was no difference in the proportion of witnessed arrests among hypertensives (12 of 25) versus normotensives (23 of 46) (P>.9). Of 25 hypertensives, 7 (28%) were cigarette smokers, compared with 17 of 46 normotensives (37%) (P>.4). None of the hypertensive coronary deaths occurred during physical exertion, and 8 of 46 normotensive deaths (17%) occurred during physical exertion (P=.04). Four of 25 hypertensives (16%) had an episode of chest pain before the arrest, compared with 14 of 46 normotensives (30%) (P=.3).
SCD With Severe Coronary Disease: Morphological Substrates of Arrhythmias, Hypertensives Versus Normotensives
Acute thrombi were present in 9 of 25 hypertensives (36%) versus 35 of 46 normotensives (76%) (P=.002). By logistic regression, hypertension was negatively associated with acute thrombus independent of the effect of the covariates age, sex, race, and heart weight (P=.01). The mechanism of thrombosis in hypertensives was plaque rupture in 78% and plaque erosion in 22% versus 60% plaque rupture and 40% plaque erosion in normotensives (P>.3). The frequencies of acute infarcts associated with acute thrombi were similar in the two groups (22% versus 20%, respectively). Cardiac hypertrophy defined as heart weight exceeding the 95% CI on the basis of age and body weight18 was present more frequently in hypertensives with acute thrombi than in normotensives with acute thrombi (89% versus 31%, P=.003).
There was no difference in the frequency of healed infarcts (70% of normotensives versus 56% of hypertensives) or acute infarcts (15% of normotensives versus 16% of hypertensives). In cases without acute thrombi, a healed or acute infarct was more frequent in hypertensives (36%) than normotensives (9%) (P=.007) (Table 2).
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Among the hypertensive patients (n=25) with severe atherosclerotic coronary disease, the culprit plaque was present in 11 left anterior descending/diagonal arteries (44%), 8 right coronary arteries (32%), 4 circumflex/obtuse marginal arteries (16%), and 1 left main artery (4%). Among normotensives, the culprit artery was left anterior descending/diagonal in 24 (52%), right coronary in 11 (24%), left circumflex/obtuse marginal in 10 (22%), and left main in 1 (2%). There was no difference in these distributions (P=.8).
In areas of acute thrombus, the mean percent cross-sectional luminal narrowing was 74±15% in normotensives and 76±14% in hypertensives (P>.5), the mean internal elastic area 10.2±4.3 mm2 for normotensives versus 16.8±7.5 mm2 for hypertensives (P=.002), and the mean residual lumen 2.6±1.8 mm2 for normotensives versus 4.0±1.7 mm2 for hypertensives (P=.08). Corrected for heart weight (in kilograms), the mean internal elastic area was 24±22 mm2/kg for normotensives versus 30±11 mm2/kg for hypertensives (P=.2). Calcified culprit plaques were present in 24 of 45 normotensives (53%) (12 grade 1, 8 grade 2, 3 grade 3, 1 grade 4) and 16 of 25 hypertensives (64%) (3 grade 1, 9 grade 2, 4 grade 3); the distribution was not significantly different in the two groups (P=.3).
SCD With Severe Coronary Disease: Heart Weight, Hypertension, and Extent of Disease
Heart weight and ratio of heart weight to body weight were significantly increased in hypertensives versus normotensives (P=.0007). Cardiac hypertrophy was present in 16 of 25 hypertensives (64%) and 15 of 46 normotensives (33%) (P=.01). Among the 25 hypertensives, one-vessel disease was present in 18 (72%), two-vessel disease in 4 (16%), and three-vessel disease in 3 (12%). Among 46 normotensives, one-vessel disease was present in 23 (51%), two-vessel disease in 15 (33%), and three-vessel disease in 7 (16%). The proportion of cases with disease in two or more vessels was lower in hypertensives (28%) than in normotensives (50%), with borderline statistical significance (P=.06).
In normotensives, heart weight in the three-vessel disease group was significantly greater than in the one-vessel disease group (P=.008). The mean heart weight among hypertensives was greatest in the one-vessel disease group (Table 3). The frequency of LVH in one-vessel hypertensives was higher than one-vessel normotensives (P=.0005) but was not significantly different in hearts with disease in two or more vessels (43% versus 48%, respectively). The frequency of acute thrombi was lower in hypertensives in both the one-vessel group (P=.005, Table 3) and the two or more–vessel group (14% versus 65%, P=.03).
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The mean heart weight increased with the presence of healed infarct (P=.004, normotensives; P=.04, hypertensives; Table 3
). For all hearts with severe atherosclerosis, the mean heart weight in patients with healed infarcts was 544±148 versus 441±107 g in those without healed infarcts (P=.001).
SCD With Severe Coronary Disease: Effect of Heart Weight on Plaque Morphology
Hearts with ruptured plaques and stable plaques were significantly heavier than those with eroded plaques. Only 1 heart with eroded plaque weighed >500 g, versus 15 of 28 hearts with plaque rupture (P=.003). The mean LV wall thickness was greater in hearts with plaque rupture than in hearts with plaque erosion (P=.003). Hearts with ruptured plaques were significantly heavier than hearts with eroded plaques in normotensives (P=.002), hypertensives (P=.06), and all cases combined (P=.0002) (Table 4). In contrast, the ratio of heart weight to body weight was increased in hearts with inactive plaques compared with both eroded and ruptured plaques (Table 4). By logistic regression analysis, increased heart weight (P=.006) and the ratio of heart weight to body weight (P=.02) were positively associated with plaque rupture independent of the covariates of age, sex, race, and smoking history.
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Discussion |
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Effect of Hypertension on Incidence of Thrombi in SCD With Severe CAD
The incidence of coronary thrombi in SCD is controversial and varies by study design and patient population. Thrombi are quite common in SCD associated with myocardial necrosis; the incidence of thrombi in SCD with acute infarcts is generally accepted to be
80%.1 2 4 19 The incidence of coronary thrombi in patients with unstable angina and SCD is the subject of controversy4 19 ; the preponderance of evidence, however, suggests a major role for acute thrombi in unstable plaques.4 20 The incidence of coronary thrombi in "instantaneous" SCD occurring in the absence of any chest pain or clinical prodrome ranges from negligible to 50%,21 22 23 24 25 suggesting that the terminal arrhythmias in such cases are not often precipitated by sudden changes in plaque morphology. All autopsies in the present study were performed by a forensic pathologist, and the deaths were almost exclusively out-of-hospital, half of them unwitnessed; only 25% of subjects had acute myocardial infarcts or known prodromal chest pain. The data in the present study demonstrate that systemic hypertension significantly affects the frequency of thrombi in SCD with severe coronary disease. The frequency of thrombi in coronary sudden death was 36% in hypertensives versus 76% in normotensives (P=.002), and systemic hypertension was negatively associated with coronary thrombosis, even when the covariates of age, sex, race, and heart weight were considered. Hypertension should be added to the list of factors (myocardial necrosis, presence and duration of chest pain) that are known to affect the incidence of thrombi in SCD with severe coronary disease.
Role of Hypertension in SCD
Although it is believed that CAD is the major cause of death in patients with hypertension and LVH,7 detailed autopsy studies on a series of hypertensive patients who died suddenly have not been performed. The present study demonstrated that patients with hypertension who died suddenly had severe coronary atherosclerosis in 69% of cases, slightly lower than normotensive patients. It is well known that hypertension accelerates the development of atherosclerotic plaque, possibly because of an interplay with other risk factors, such as diabetes and hypercholesterolemia,26 as well as hemodynamic effects of increased shear stress on the endothelial surface of epicardial arteries.27 Therefore, one might expect that, in a population who died suddenly, there would be an increased frequency and extent of severe CAD compared with a normotensive population, which is not the case. Indeed, although of borderline statistical significance, the extent of disease in our hypertensive group with severe coronary disease was less than that of normotensives, 72% of hypertensives having one-vessel disease versus 50% of normotensives. In addition, hypertensives were significantly older than normotensives; the reverse might be expected if hypertension accelerated atherosclerotic SCD.
The lower degree of epicardial coronary disease and the decreased frequency of acute coronary thrombus in hypertensives suggest other mechanisms of SCD in hypertensives. In this study, the high incidence of LVH in hypertensives compared with normotensives (64% versus 33%), especially in those with one-vessel disease (72% versus 17%), is evidence that cardiomegaly played a role in SCD in hypertensive individuals. The high prevalence of one-vessel disease (up to 10%) found at autopsies in individuals who died of noncardiac causes, compared with 4% for two- and three-vessel disease,24 indicates that one-vessel disease in the absence of thrombosis is often not causatory in SCD and may be an incidental finding. The high incidence of LVH in hypertensive SCD in this study corroborates data indicating that LVH increases the risk of ventricular arrhythmias in patients with severe CAD.5 6 7 8 9
In addition to LVH and epicardial coronary atherosclerosis, other myocardial processes may cause myocardial ischemia and arrhythmias in hypertensive patients. Hypertension is associated with interstitial and perivascular fibrosis28 29 as well as a coronary microangiopathy, even in the absence of LVH.30 31 Iriarte et al30 demonstrated that of 18 hypertensive patients with LVH and angina, only 7 (38%) had epicardial disease by angiography, the remaining patients suffering from presumed microvascular angina. Reduced coronary vasodilator reserve in hypertensive patients appears to be a function of arteriolar thickening and periarteriolar fibrosis29 31 32 and may occur in the absence of LVH.33 Reduced coronary reserve may make hypertensives more susceptible to the ischemic effects of severe epicardial coronary narrowing. In the present study, a larger proportion of hypertensive SCD with severe CAD was associated with infarcts (acute or healed) in the absence of thrombi (36% versus 9%). These data suggest that the myocardium of hypertensives is more susceptible to arrhythmias, which probably lead to sudden death in the setting of severe CAD, compared with normotensives.
Nitenberg and Antony27 did not find a significant increase in epicardial coronary luminal diameter by quantitative angiography diameter as a compensatory mechanism in hypertensives. In the present study, however, at the site of thrombosis, the area enclosed by the internal elastic lamina was greater in hypertensives than normotensives, although the lumen size was similar. The finding of increased area enclosed by the internal elastic lamina in hypertensives suggests that acute thrombi may not be as lethal in hypertensives as in normotensives.
Cardiac Hypertrophy and Morphology of Coronary Artery Plaque
Previous studies of SCD have not consistently demonstrated increased heart weight in hearts lacking thrombi compared with those with thrombi.1 The present study demonstrated that, expressed as heart weight/body weight percent, hearts with stable plaques were heavier than those with thrombi originating in both eroded and ruptured plaques. This finding is consistent with the negative correlation between hypertension and acute thrombi as discussed above. The present study also demonstrates that the effect of heart weight on acute thrombi in SCD is influenced by the type of thrombus. Increased heart weight was an independent predictor of plaque rupture with superimposed thrombus in the present study. Eroded plaques with thrombi occurred in smaller hearts, expressed both as heart weight and ratio of heart weight to body weight, compared with hearts with plaque rupture.
These results support distinct mechanisms for plaque rupture and plaque erosion in the genesis of coronary thrombosis in SCD with severe coronary disease.25 Plaque erosions occur in younger patients25 and in smaller hearts than plaque ruptures, suggesting that they may occur earlier and may contribute to early plaque progression. Plaque rupture appears to be more important in later stages of plaque progression, after ischemic cardiomegaly has occurred with increased plaque burden. Alternatively, the hypertrophied heart may be more likely to cause mechanical plaque disruption and rupture, possibly as a result of increased forces generated in systole or through endothelial injury from eddies generated by increased luminal pressure.
Cardiac Hypertrophy and Degree of Epicardial Atherosclerosis in SCD
The present study demonstrates that in SCD with severe coronary disease, hearts with healed infarcts were heavier than those without healed infarcts. These findings corroborate data of Roberts et al34 and Rompannen et al.35 This relationship was seen in hypertensive hearts as well as normotensive hearts, although the difference was more marked in normotensives.
It has been established that patients who die suddenly with one-vessel disease are younger than those with three-vessel disease.36 However, the association between heart weight and degree of epicardial atherosclerosis is controversial.34 35 36 Roberts et al34 found no correlation between number of narrowed coronary arteries and heart weight. In contrast, Warnes and Roberts36 found that hearts weighing >450 g were more likely to have diffuse disease, as expressed by mean percent of severely narrowed segments, than hearts weighing <450 g. Rompannen et al35 found no correlation between heart weight and number of coronary arteries severely narrowed by atherosclerotic plaque, and Dean and Gallagher37 found a significant correlation between cardiac weight and the number of major coronary arteries severely narrowed.
The present study suggests that the discrepancy in the studies may be resolved by considering the effect of systemic hypertension. We demonstrated a correlation between the degree of epicardial atherosclerosis and heart weight in normotensive hearts and not hypertensive hearts, suggesting that the effects of hypertension on heart weight may obscure the association between ischemic hypertrophy and the degree of epicardial disease. The numbers of patients with hypertension were not recorded in the previous studies,34 35 36 indicating that the effect of hypertensive cardiac hypertrophy was not assessed. The findings in the present study indicate that both the degree of epicardial atherosclerosis and the presence of myocardial scarring are associated with increased heart weight, corroborating an association between ischemia and cardiac hypertrophy.
Limitations of the Present Study
Although this study clearly demonstrates that there are different mechanisms in hypertensives versus normotensives in a large proportion of SCD with severe CAD, there are several factors that need further study. The role of other risk factors, especially hyperlipidemia, needs to be addressed in conjunction with the role of hypertension on plaque morphology in SCD. In addition, the role of microvascular disease as well as interstitial fibrosis has yet to be studied at a morphological level in hypertensives who die suddenly, compared with normotensives.
Implications of the Present Study
The interrelations of hypertension, ischemic cardiac hypertrophy, degree of epicardial disease, and type of coronary plaque have two basic implications. First, this study suggests that in the majority of hypertensive SCDs, epicardial coronary disease and myocardial disease probably play a concomitant role in the mechanism of death. To prevent SCD in hypertensive patients, reduction of LV mass and prevention of epicardial coronary stenoses are critical. Second, there is a proportional relationship between the degree of epicardial coronary disease and heart weight in normotensives, suggesting that increases in cardiac mass may serve as a marker for progression of CAD in patients with known coronary atherosclerosis. Further, there appears to be a relationship between mechanism of coronary thrombosis and heart weight. In normotensives, SCD is likely to occur either during plaque erosion, especially in younger patients with normal-sized hearts and one- or two-vessel disease, or in hearts with plaque rupture, especially in older patients with hypertrophied hearts and two- or three-vessel disease.
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Footnotes |
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Reprint requests to Renu Virmani, MD, Chairperson, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000.
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army, the Department of the Air Force, or the Department of Defense.
Received April 11, 1996; revision received July 12, 1996; accepted July 18, 1996.
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