The role of systolic blood pressure (SBP) as an independent risk factor for sudden cardiac death (SCD) is not well defined in a general population. Thus, we assessed the association between BP at rest and risk of SCD. BP and other risk factors were measured in a representative population-based sample of 2,666 Finnish men (42 to 61 years of age). During an average follow-up period of 18.9 years (interquartile range 17.9 to 22.6), 213 SCDs occurred. Each increment 10-mm Hg of SBP at rest was associated with an increased risk of SCD (relative hazard 1.15, 95% confidence interval 1.07 to 1.25, p <0.001) after adjustment for age, alcohol consumption, cigarette smoking, serum low-density lipoprotein cholesterol, type 2 diabetes, body mass index, left ventricular hypertrophy, previous myocardial infarction, family history of coronary heart disease, and use of antihypertensive medications. Men with increased SBP of >145 mm Hg had a 2.04-fold (95% confidence interval 1.23 to 2.52, p = 0.003) adjusted risk for SCD compared to those with SBP <123 mm Hg. In conclusion, this study emphasizes the importance of the definition of SBP at rest because it provides a valuable prognostic measurement for SCD.
There is very limited information on the relation between the conventional assessment of systemic blood pressure (BP) and risk of sudden cardiac death (SCD) in the general population. Because increased BP is related to an increased risk of arrhythmias, left ventricular hypertrophy, and other cardiovascular outcomes, a relation between BP and SCD might be expected. Predictors of SCD are particularly important because SCD typically occurs shortly after the onset of symptoms, leaving little time for effective medical interventions. Therefore, clinically useful markers of increased risk for SCD assume importance because prevention appears to be the most viable approach to decrease substantially the risk of SCD at the population level. The value of a clinically useful and common measurement such as BP would be clear if an increased systolic BP (SBP) or diastolic BP (DBP) were shown to be important risk markers for sudden cardiac arrest. The present study was designed to show the prognostic significance and discriminative power of BP at rest with regard to risk of future SCD in a representative population-based sample of men.
Methods
This study was designed to investigate risk predictors for atherosclerotic cardiovascular outcomes in a population-based sample of men from eastern Finland. The focus of the present prospective study was on risk markers for SCD in a general population. The study population was a representative sample of men living in the city of Kuopio and its surrounding rural communities who were 42 to 60 years of age at baseline examinations performed from March 1984 through December 1989. Of 3,235 potentially eligible men, 2,682 (83%) participated in this study. The Kuopio Ischemic Heart Disease (KIHD) risk factor study was approved by the research ethics committee of the University of Eastern Finland, and each participant gave written informed consent. The present study is based on data obtained in 2,666 participants who had complete data on BP.
BP at rest was measured by an experienced nurse using a sphygmomanometer (Hawsksley, United Kingdom) after 5 and 10 minutes of rest in a seated position in a quiet room from 8:00 to 10:00 a.m. The BP measurement protocol on the first examination day was 15 minutes of supine rest with BP measured at minutes 5, 10, and 15; standing at rest with 1 BP reading taken after 1 minute; and 10 minutes of seated rest with BP measured at minutes 5 and 10. The mean of these 6 values was used as mean BP at rest. Hypertension at rest was defined as hypertension confirmed by current use of antihypertensive medication and/or SBP >140 mm Hg and/or DBP >90 mm Hg.
The collection of blood specimens and measurement of fasting levels of serum lipids and assessment of smoking, alcohol consumption and the definition of diabetes mellitus are described elsewhere. Body mass index was computed as weight in kilograms divided by the square of height in meters. Baseline diseases, family histories, and use of medications were assessed by self-administered questionnaires. Information about chronic diseases was checked during a medical examination. Coronary intervention (n = 391) was defined as percutaneous coronary intervention and/or coronary artery bypass surgery during follow-up. All deaths that occurred by the end of 2008 were derived from hospital documents, wards of health centers, and death certificates. Sources of information were interviews, hospital documents, death certificates, autopsy reports, and medicolegal reports. There were no losses to follow-up.
A death was determined a SCD when it occurred within 1 hour of the onset of an abrupt change in symptoms (witnessed cardiac arrest) or within 24 hours of the time that the patient was last seen alive in his normal state of health when autopsy data did not reveal a noncardiac cause of sudden death. Subjects who were successfully resuscitated from ventricular tachycardia (VT) and/or ventricular fibrillation (VF) were also defined as having SCD (n = 15). Deaths from aortic aneurysm rupture, cardiac rupture or tamponade and pulmonary embolism, cancer, or other noncardiac co-morbidities were not included as SCDs. Diagnostic classification of events was based on symptoms, electrocardiographic findings, cardiac enzyme elevations, autopsy findings (80%), and history of coronary heart disease together with clinical and electrocardiographic findings of the paramedic staff. Thus, we had available all hospital documents including medical records and laboratory and electrocardiographic findings from hospital and paramedical staff and use of medications and defibrillator. Suspected SCD cases were checked from deaths from cardiovascular causes with the help of all documents. Other cardiac-related deaths were defined as non-SCDs. Documents related to deaths were cross checked in detail by 2 physicians. The independent events committee that performed classification of deaths was blinded to clinical data.
Descriptive data are presented as mean and percentage. Correlations between BPs at rest were analyzed using Pearson correlations. To demonstrate the prognostic value of BP, it was entered into forced Cox proportional hazards models (SPSS, Inc., Chicago, Illinois). Cox models were adjusted for age and other covariates that were selected based on their previously established role as well-defined predictive factors from overall evidence and available data. After analysis of categorized BP values, subjects were divided into 4 groups based on the distribution of BPs observed in the study sample. Quartiles were slightly uneven because SBP and DBP were measured to the nearest BP value.
Relative hazards, adjusted for risk factors, were estimated as antilogarithms of coefficients from multivariable models. Fit of proportional hazards models was examined by plotting hazard functions in different categories of risk factors over time. Proportional hazards assumption was verified for all variables by the inspection of plots of Schoenfeld residuals for covariates. Cumulative survival from SCD according to groups of SBP was calculated using the Kaplan–Meier method. A p value <0.05 was considered statistically significant. These statistical analyses were performed using SPSS 18.0 for Windows.
C-statistics was calculated to assess model discrimination, i.e., the ability of the model to correctly identify subjects with respect to SCD. The Harrell C-index was the primary measurement of discrimination. From c-statistics, the incremental value of SBP in addition to previously documented risk factors and diseases were evaluated.
Results
At beginning of the study, the subjects’ mean age was 53 years. An average SBP at rest was 134 mm Hg, whereas mean DBP at rest was 88 mm Hg. Other baseline characteristics are listed in Table 1 . Mean SBP at rest had a positive correlation with mean DBP (r = 0.751, p <0.001), and SBP and DBP measured while sitting correlated significantly (r = 0.739, p <0.001).
| Age (years) | 53.0 ± 5.1 |
| Body mass index (kg/m 2 ) | 26.9 ± 3.5 |
| Waist-to-hip ratio | 0.95 ± 0.06 |
| Smokers | 31.9% |
| Cigarette smoking (pack-years) ⁎ | 8.4 ± 16.5 |
| Alcohol consumption (g/week) | 74.2 ± 121.4 |
| Serum total cholesterol | |
| mmol/L | 5.91 ± 1.07 |
| mg/dl | 228.5 ± 41.4 |
| Serum low-density lipoprotein | |
| mmol/L | 4.04 ± 1.01 |
| mg/dl | 156.2 ± 39.1 |
| Serum high-density lipoprotein | |
| mmol/L | 1.29 ± 0.30 |
| mg/dl | 49.9 ± 11.6 |
| Serum triglycerides | |
| mmol/L | 1.28 ± 0.82 |
| mg/dl | 113.4 ± 24.6 |
| Systolic blood pressure (mm Hg) | 134.0 ± 16.8 |
| Diastolic blood pressure (mm Hg) | 88.4 ± 10.5 |
| Blood glucose (mmol/L) | 4.77 ± 1.18 |
| Serum insulin (mU/L) | 11.6 ± 7.0 |
| Cardiorespiratory fitness (ml/kg/min) | 30.2 ± 8.0 |
| High-sensitivity C-reactive protein (mmol/L) | 2.28 ± 3.35 |
| Coronary heart disease | 23.8% |
| Previous myocardial infarction | 7.4% |
| Family history of coronary heart disease | 49.3% |
| Coronary interventions | 0.6% |
| History of hypertension | 30.1% |
| Family history of hypertension | 47.4% |
| Cardiac insufficiency † | 6.6% |
| Cardiomyopathy † | 2.1% |
| Cerebrovascular disease | 2.4% |
| Claudication | 3.8% |
| Arrhythmias ‡ | 15.8% |
| Pulmonary disease § | 12.5% |
| Cancer | 1.6% |
| Type 2 diabetes | 5.1% |
| Regular use of medications | |
| Antihypertensive medication | 22.4% |
| Medication for dyslipidemia | 8.6% |
| β Blocker | 18.2% |
| Acetyl salicylic acid | 6.9% |
⁎ Pack-years denotes lifelong exposure to smoking, which was estimated as the product of years smoked and number of tobacco products smoked daily at time of examination.
† Diagnoses of cardiac insufficiency and cardiomyopathy were based on clinical findings and symptoms and/or echocardiographic findings.
‡ Arrhythmias included extrasystole, regular or paroxysmal atrial fibrillation, and supraventricular tachycardia.
§ Pulmonary diseases included bronchial asthma, chronic obstructive pulmonary disease, and pulmonary tuberculosis.
There were 213 SCDs including subjects who were successfully resuscitated from VT/VF during an average follow-up period of 18.9 years (interquartile range 17.9 to 22.6). In total 161 SCDs (75% of all events) occurred in out-of-hospital conditions, and most of these cases were from documented VT, VF, or death with autopsy examination revealing no other reason for death. The number of those with an implantable defibrillator was 7.
As a continuous variable, a 10-mm Hg increment in SBP was related to a 1.15-fold risk of SCD after adjustment for age, alcohol consumption, cigarette smoking, serum low-density lipoprotein cholesterol, type 2 diabetes, left ventricular hypertrophy, body mass index, previous myocardial infarction, family history of coronary heart disease, and use of antihypertensive medications ( Table 2 ). Further adjustment for corrected QT interval on electrocardiogram, family history of hypertension, and cardiorespiratory fitness did not attenuate the significance of the relation between SBP or DBP and risk of SCD. As presented in Table 2 , assessments of SBP and DBP were associated with SCD whether BP was measured in the sitting or supine position, although standing DBP was not related to SCD.
| RR ⁎ | 95% CI | p Value | |
|---|---|---|---|
| Systolic blood pressure at rest † | 1.15 | 1.07–1.25 | <0.001 |
| Sitting | 1.13 | 1.05–1.21 | <0.001 |
| Supine | 1.16 | 1.07–1.26 | <0.001 |
| Standing | 1.09 | 1.01–1.18 | 0.027 |
| Diastolic blood pressure at rest † | 1.17 | 1.02–1.35 | 0.021 |
| Sitting | 1.14 | 1.01–1.30 | 0.048 |
| Supine | 1.22 | 1.06–1.42 | 0.006 |
| Standing | 1.08 | 0.95–1.24 | 0.229 |
⁎ Relative risks (95% confidence intervals) were adjusted for age, alcohol consumption, cigarette smoking, serum low-density lipoprotein cholesterol, type 2 diabetes, body mass index, left ventricular hypertrophy, previous myocardial infarction, family history of coronary heart disease, and use of antihypertensive medications.
† The mean of 6 assessments was used as mean blood pressure at rest. Blood pressure as a continuous variable was included in the model.
In addition to continuous variable analyses, SBP and DBP were significant predictors of SCD as classified in quartiles. SBP and DBP in quartiles were directly related to risk of SCD ( Table 3 ). When all coronary interventions owing to obstructive coronary artery disease during follow-up were taken into account, risk of SCD was 2.12-fold (95% confidence interval [CI] 1.42 to 3.17, p <0.001) in men with SBP of >145 mm Hg compared to men with SBP of <123 mm Hg. The respective risk was 1.97 (95% CI 1.32 to 2.94, p = 0.001) after additional adjustment for corrected QT interval, family history of hypertension, and cardiorespiratory fitness. Kaplan–Meier curves for SCD according to quartiles of SBP diverged as the follow-up continued ( Figure 1 ) .
| SCD | All-Cause Death | |||
|---|---|---|---|---|
| RR (95% CI) † | p Value | RR (95% CI) † | p Value | |
| Systolic blood pressure | ||||
| First quartile <123 mm Hg (n = 660) | 1.00 (reference) | 1.00 (reference) | ||
| Second quartile 123–132 mm Hg (n = 677) | 0.96 (0.61–1.50) | 0.841 | 1.09 (0.88–1.36) | 0.432 |
| Third quartile 133–145 mm Hg (n = 666) | 1.25 (0.82–1.92) | 0.304 | 1.14 (0.92–1.42) | 0.242 |
| Fourth quartile >145 mm Hg (n = 663) | 2.04 (1.37–3.03) | <0.001 | 1.49 (1.21–1.84) | <0.001 |
| Diastolic blood pressure | ||||
| First quartile <82 mm Hg (n = 659) | 1.00 (reference) | 1.00 (reference) | ||
| Second quartile 82–88 mm Hg (n = 675) | 1.03 (0.68–1.56) | 0.898 | 0.85 (0.69–1.05) | 0.140 |
| Third quartile 88–95 mm Hg (n = 662) | 1.24 (0.82–1.85) | 0.308 | 0.88 (0.71–1.08) | 0.219 |
| Fourth quartile >95 mm Hg (n = 670) | 1.60 (1.06–2.41) | 0.025 | 1.16 (0.94–1.42) | 0.177 |
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