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Antecedent Hypertension Confers Increased Risk for Adverse Outcomes After Initial Myocardial Infarction

Agha W. Haider, Leway Chen, Martin G. Larson, Jane C. Evans, Ming Hui Chen, Daniel Levy
https://doi.org/10.1161/01.HYP.30.5.1020
Hypertension. 1997;30:1020-1024
Originally published November 1, 1997

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Abstract

Abstract Several studies have examined the association of blood pressure (BP) after myocardial infarction (MI) with a risk for adverse outcome; however, few studies have investigated prognosis after MI as a function of BP before MI. Our goal was to examine the relation of antecedent hypertension to risk of adverse outcomes after initial MI. From 1967 to 1990, 404 subjects followed at the Framingham Heart Study developed an initial MI. These subjects were classified on the basis of preinfarction BP into normotensive (BP<140/90 mm Hg and not receiving antihypertensive treatment; n=118), stage I–untreated hypertension (BP 140 to 159/90 to 99 mm Hg; n=89), and stage II to IV or treated hypertension (BP ≥160/100 mm Hg or treated hypertension; n=197). Cox models were used to adjust for age, sex, smoking, glucose intolerance, total cholesterol, and prior cardiovascular disease. Antecedent hypertension was related to risk of adverse outcome after MI. Compared with normotensive individuals, stage II to IV hypertensives were at increased risk for reinfarction (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.20 to 4.04). A similar but nonsignificant association was seen in stage I hypertensives (HR, 1.91; 95% CI, 0.97 to 3.77). Stage II to IV hypertensives were at increased risk for all-cause mortality compared with normotensive persons (HR, 1.45; 95% CI, 1.07 to 1.98). Thus, even after MI, a history of antecedent hypertension remains predictive of adverse outcome. These findings are consistent with beneficial effects of BP control in primary and secondary prevention settings. Effective BP control may both reduce the risk for an initial MI and improve outcome in the event that an MI occurs.

Hypertension is a highly prevalent condition and a major contributor to atherosclerotic cardiovascular diseases, including heart failure, coronary heart disease, stroke, and peripheral vascular disease.1 Coronary heart disease, including myocardial infarction, is the most common and most lethal cardiovascular sequela of hypertension.1 2 Several clinical studies have examined the association of blood pressure with risk of adverse outcome in patients with myocardial infarction.3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 These studies have reported an adverse association of hypertension documented either before4 5 6 7 8 10 11 12 13 14 15 16 17 or after acute myocardial infarction3 5 9 18 19 20 21 with postinfarction outcome. Most of these studies were carried out in selected patient populations6 7 8 11 12 13 14 15 16 17 18 20 21 and may not be representative of the general population. Furthermore, assessment of blood pressure recorded in the early infarction period may not reflect true hypertension status.22 23 To the best of our knowledge, no study has examined the association of antecedent hypertension with recurrent myocardial infarction, coronary heart disease death, and all-cause mortality, after an initial myocardial infarction.

The purpose of this study was to examine the association of antecedent hypertension with risk for adverse outcomes after initial myocardial infarction in participants in the Framingham Heart Study. This study sample is less fraught with the biases inherent in hospital- or clinic-based reports.

Methods

Study Population

Since 1948, the Framingham Heart Study has followed participants at regular intervals as part of a prospective population-based investigation of cardiovascular disease. Study design and recruitment procedures have been published previously: 5209 men and women 28 to 62 years of age were enrolled.24 Every 2 years a follow-up visit included a medical history, physical examination, blood pressure measurements, 12-lead electrocardiogram, and laboratory tests.

Beginning in 1971, the Framingham Offspring Study enrolled 5124 men and women who were offspring or spouses of offspring of original Framingham Heart Study subjects. Study design and recruitment procedures have been published.25 The second, third, and fourth Framingham Offspring Study examinations were conducted 8, 12, and 16 years, respectively, after the initial examination cycle. To reflect more contemporary experience, Framingham Heart Study clinic examinations 11 through 20 (1967 to 1989) and Framingham Offspring Study visits 1 through 4 (1971 to 1992) were used.

Methodology for assessing risk factors has been published previously.26 Briefly, data for selected risk factors were obtained from the most recently attended clinic examination preceding an initial myocardial infarction. Risk factors including age, sex, height and weight, blood pressure, antihypertensive medication use, total serum cholesterol, glucose intolerance, and cigarette smoking were documented for each participant. Body mass index (kg/m2) was used as a measure of obesity. Sitting systolic and diastolic blood pressures were measured twice by a physician using a mercury column sphygmomanometer and averaged. Glucose intolerance was present if any of the following conditions were met: (1) if diabetes mellitus was diagnosed at clinic examination, (2) if glucose was present in the urine sample at the clinic examination, or (3) if a random nonfasting blood glucose value was 7.8 mmol/L (140 mg/dL) or greater. Serum total cholesterol mmol/L (mg/100 mL) was measured by the Abell-Kendal method. Participants were categorized as smokers if they currently smoked cigarettes or if they had quit within 1 year before the clinic examination.

Clinical Data and Outcomes

Subjects were classified into three categories on the basis of blood pressure at the examination before their first myocardial infarction. Normotensive subjects had systolic blood pressures less than 140 mm Hg and diastolic blood pressures less than 90 mm Hg and were not current users of antihypertensive therapy. Hypertensive subjects were categorized into stage I, defined as systolic blood pressure 140 to 159 mm Hg or diastolic blood pressure 90 to 99 mm Hg in subjects not receiving antihypertensive treatment, and stage II to IV, defined as systolic blood pressure 160 mm Hg or more or diastolic blood pressure 100 mm Hg or more, or current use of antihypertensive therapy.27

The following outcomes were evaluated: (1) recurrent myocardial infarction; (2) death from coronary heart disease; and (3) all-cause mortality. A secondary analysis excluding the first 30 days of follow up after myocardial infarction also was performed.

Criteria for myocardial infarction have been described previously.26 At each clinic examination a history of interim hospitalizations and symptoms of heart disease were recorded. Outside medical records of participants who did not attend an examination were obtained and evaluated for interim myocardial infarction. All suspected interim events were evaluated by a panel of three physicians who reviewed relevant Framingham Heart Study clinic notes, hospitalization records, and pathology reports. Myocardial infarction was diagnosed when at least two of the following criteria were fulfilled: (1) symptoms consistent with myocardial infarction; (2) electrocardiographic changes of acute myocardial infarction; and (3) diagnostic elevation of cardiac enzymes. To minimize selection bias and to ensure precision in the dating of infarctions, unrecognized myocardial infarctions28 were excluded from this study. The electrocardiographic definition of left ventricular hypertrophy has been published.29 30 Left ventricular hypertrophy was present when increased voltage was associated with major ST-T repolarization changes (“strain” pattern).

Death was documented by a death certificate. Additional information was obtained from records supplied by hospital attending physician, pathologist, medical examiner, or family. A panel of three physicians reviewed all evidence to arrive at the cause of death. Death from cardiovascular disease was designated when any disease of the heart or blood vessels was considered responsible.26

Statistical Analysis

Descriptive data are presented as percentages or mean±SD. Statistical analysis was performed using SAS software (SAS Institute Inc).31 Proportional hazards regression models were used to examine the relations of antecedent hypertension status to outcomes after myocardial infarction.32 Analyses were adjusted for age, sex, cigarette smoking, electrocardiographic left ventricular hypertrophy, glucose intolerance, total serum cholesterol, and prior cerebrovascular disease, intermittent claudication or congestive heart failure. Hazard ratios (HR) and 95% confidence intervals (CI) were computed.

Results

From 1967 to 1990 a total of 404 subjects developed an initial myocardial infarction (266 men and 138 women). Mean age at the time of infarction was 66.5 years (range, 40 to 91 years). Of the 404 initial infarctions, 303 were Q-wave myocardial infarction and 101 were non–Q wave. Characteristics of study subjects, according to hypertension status before myocardial infarction, are presented in the Table⇓. One hundred forty-two (72%) subjects with stage III to V hypertension were on antihypertensive therapy. Mean age increased progressively with increasing blood pressure levels, and there was a higher proportion of women in the stage II to IV hypertension group. Prevalence of left ventricular hypertrophy and other cardiovascular disease was higher in stage II to IV hypertensive subjects.

View this table:
Table 1.

Risk Factors Before Initial Myocardial Infarction According to Hypertension Classification

Median survival after initial myocardial infarction was 7.85 years. During follow-up (range, 1 day to 26.6 years), 86 subjects experienced a recurrent myocardial infarction, 142 died from coronary heart disease, and 144 died from other causes. A total of 63 individuals did not survive more than 30 days after myocardial infarction (Fig 1⇓).

Figure 1.
Figure 1.

Outcomes after initial myocardial infarction (MI). End points shown are not mutually exclusive. CHD indicates coronary heart disease.

Post–myocardial infarction survival differed among the three groups (Fig 2⇓): median survival was 12.19 years, 8.88 years, and 4.18 years among normotensives, stage I, and stage II to IV hypertensives, respectively. Compared with subjects who were normotensive before myocardial infarction, stage I hypertensives were at marginally increased risk for reinfarction (HR, 1.91; 95% CI, 0.97 to 3.77), and stage II to IV hypertensives were at significantly increased risk for reinfarction (HR, 2.20; 95% CI, 1.20 to 4.04). Subjects with stage II to IV hypertension also were at increased risk for all-cause mortality compared with normotensives (HR, 1.45; 95% CI, 1.07 to 1.98). Neither stage I nor stage II to IV hypertension was associated with increased risk for coronary heart disease death (Fig 3⇓).

Figure 2.
Figure 2.

Survival after myocardial infarction according to blood pressure status before infarction. Kaplan-Meier curves for survival after initial myocardial infarction for normotensive individuals (systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg and not receiving antihypertensive therapy), stage I hypertensive individuals (systolic blood pressure 140 to 159 mm Hg or diastolic blood pressure 90 to 99 mm Hg and not receiving antihypertensive treatment), and stage II to IV hypertensive individuals (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg or current use of antihypertensive therapy). Median survival times were 12.19 years, 8.88 years, and 4.18 years, respectively.

Figure 3.
Figure 3.

Comparison of outcomes of interest in stage I (systolic blood pressure 140 to 159 mm Hg or diastolic blood pressure 90 to 99 mm Hg and no antihypertensive therapy) and stage II to IV hypertensive individuals (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg or current use of antihypertensive therapy) vs normotensive individuals. Hazard ratios and 95% confidence limits are presented. Results are based on multivariaate proportional hazards regression adjusting for age, sex, cigarette smoking, electrocardiographic left ventricular hypertrophy, glucose intolerance, total serum cholesterol, and prior cerebrovascular disease, intermittent claudication, or congestive heart failure. MI indicates myocardial infarction; CHD, coronary heart disease; and CI, confidence interval.

Similar results were observed when events occurring within the first 30 days after initial infarction were excluded from analysis (Fig 4⇓). Subjects with stage I and stage II to IV hypertension were at increased risk for recurrent infarction compared with normotensives (HR, 2.75; 95% CI, 1.26 to 6.01 and HR, 2.88; 95% CI, 1.39 to 5.94, respectively). Subjects with stage II to IV hypertension also were at greater risk for all-cause mortality compared with normotensives (HR, 1.69; 95% CI, 1.19 to 2.39).

Figure 4.
Figure 4.

Comparison of outcomes of interest in stage I (systolic blood pressure 140 to 159 mm Hg or diastolic blood pressure 90 to 99 mm Hg and no antihypertensive therapy) and stage II to IV hypertensive individuals (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg or current use of antihypertensive therapy) vs normotensive individuals. Outcomes within 30 days after initial myocardial infarction were excluded. Hazard ratios and 95% confidence limits are presented. Results are based on multivariate proportional hazards regression adjusting for age, sex, cigarette smoking, electrocardiographic left ventricular hypertrophy, glucose intolerance, total serum cholesterol, and prior cerebrovascular disease, intermittent claudication, or congestive heart failure. MI indicates myocardial infarction; CHD, coronary heart disease; and CI, confidence interval.

Discussion

This long-term follow-up study of a carefully monitored cohort supports the hypothesis that antecedent hypertension is a risk factor for adverse outcome after initial myocardial infarction. An association with adverse outcome was particularly strong for recurrent myocardial infarction. In addition, the hazards for adverse outcomes after myocardial infarction increased with increasing stages of hypertension, and the increased risks were more pronounced after excluding early postinfarct events. These findings may provide insight into complications of hypertensive heart disease.

Prior investigations from the Framingham Heart Study reported that the risk of adverse outcomes is increased in persons with elevated blood pressure after myocardial infarction.5 9 Similarly, others have shown that elevated blood pressure after myocardial infarction is associated with adverse outcomes,3 18 19 including increased risk for cardiac death and all-cause mortality.19 In contrast, the Coronary Drug Project investigators did not find an independent association between systolic or diastolic blood pressure recorded 3 months after myocardial infarction and adverse outcomes in men followed for 5 years.20 Similarly, Sanz et al reported that systolic aortic pressure recorded one month after myocardial infarction was not an independent predictor of survival.21

Previous studies of the influence of antecedent hypertension on prognosis after myocardial infarction do not provide consistent results.4 5 6 7 8 10 11 12 13 14 15 16 17 Herlitz et al reported that a history of prior hypertension remained an independent indicator of reinfarction during 5-year follow-up in patients admitted with acute myocardial infarction.13 Tofler and coworkers reported that in elderly patients with myocardial infarction a history of antecedent hypertension was a significant predictor of 4-year mortality.14 In contrast, others found no association16 or only a borderline association with adverse outcome after myocardial infarction.17 Prior studies were clinic-based or hospital-based case series, which are prone to selection bias, and the duration of follow-up in these studies was limited. Most of these studies had to rely on a history of prior elevated blood pressure or measurements that were obtained during hospitalization. There have been few population-based studies that measured blood pressure before myocardial infarction. In 2336 men in the Framingham Heart Study cohort, blood pressure status preceding the first myocardial infarction was related to survival.5 That report was based on a smaller number of initial myocardial infarctions (193 versus 404) and did not include women. Furthermore, in the present study mean follow-up was of longer duration (mean of 7.85 versus 5 years) and included evaluation of recurrent myocardial infarction, coronary heart disease death, and all-cause mortality as end points.

Antecedent hypertension may portend adverse outcome after myocardial infarction because of its multiple associations. Hypertensive persons tend to have a higher prevalence of other risk factors1 3 33 that, in addition to their high blood pressure, predisposes them to cardiovascular disease. Furthermore, the adverse effects of hypertension increase across blood pressure levels with no threshold effect.3 Therefore, when they present with myocardial infarction, patients with antecedent hypertension may have more advanced atherosclerosis and a greater burden of risk factors compared with those who have normal blood pressure. Similarly, they are more likely to have a higher prevalence of other comorbid conditions and a greater likelihood of hypertension-related end-organ damage. To account for these concerns, our study adjusted for age, sex, smoking, electrocardiographic left ventricular hypertrophy, glucose intolerance, total cholesterol level, and prior cardiovascular disease.

Blood pressure is one of the major determinants of myocardial oxygen demand; and in patients with elevated blood pressure, coronary occlusion is likely to result in larger infarcts and more extensive myocardial damage. This may be compounded by preexisting coronary artery disease and endothelial dysfunction.34 Larger myocardial infarctions are likely to result in greater left ventricular dysfunction, a major determinant of poor prognosis.35

The Framingham Heart Study provides a large, population-based sample in which hypertension and other risk factors are routinely assessed at periodic examination cycles. The follow up was extensive and is ongoing with consistent application of uniform criteria. The study includes both men and women and consists of a population-based sample in which referral bias is inherently low.

Some limitations of the present study need to be considered. Detailed information on medical treatment and blood pressure at the time of infarction and after myocardial infarction was not available. Distinction was not made regarding the location of myocardial infarction; however, the presence or absence of Q-wave infarction did not appear to influence outcome. This study was underpowered to examine coronary heart disease death; although the point estimates for coronary heart disease death were increased among hypertensive subjects, they were not statistically significant. Finally, due to the racial and ethnic composition of the study sample, these findings may not be generalizable to other groups.

In conclusion, antecedent hypertension is a risk factor for adverse outcome after initial infarction, especially for recurrent myocardial infarction. This risk increases with increasing hypertension stage and is stronger after excluding early events. These findings may have implications for primary and secondary prevention; among hypertensive patients, more effective blood pressure control may reduce the risk for an initial myocardial infarction and improve outcome in the event that a myocardial infarction occurs.

Acknowledgments

This investigation was supported by NIH/NHLBI contract NO1-HC-38038. Dr Haider, MD, PhD, is the recipient of the Sue McCarthy Travel Award of the British Hyperlipidemia Association. We are indebted to Honey Flynn and Sandra Clevesy for library assistance and literature retrieval.

Footnotes

  • Presented in part at the 68th Annual Scientific Sessions of the American Heart Association Anaheim, California, November 13-15, 1995, and published in abstract form (Circulation. 1995;92[suppl I]:I-519).

  • Received March 25, 1997.
  • Revision received April 15, 1997.
  • Accepted June 6, 1997.

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  • Antecedent Hypertension Confers Increased Risk for Adverse Outcomes After Initial Myocardial Infarction
    Agha W. Haider, Leway Chen, Martin G. Larson, Jane C. Evans, Ming Hui Chen and Daniel Levy
    Hypertension. 1997;30:1020-1024, originally published November 1, 1997
    https://doi.org/10.1161/01.HYP.30.5.1020
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