ORIGINAL ARTICLE. F Hadaegh 1, R Mohebi 1, D Khalili 1,2, M Hasheminia 1, F Sheikholeslami 1 and F Azizi 3

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1 Journal of Human Hypertension (2013) 27, All rights reserved /13 ORIGINAL ARTICLE for cardiovascular disease among middle-aged but not in elderly populations: 9-year results of a population-based study F Hadaegh 1, R Mohebi 1, D Khalili 1,2, M Hasheminia 1, F Sheikholeslami 1 and F Azizi 3 Data are conflicting and sparse regarding the impact of high normal blood pressure (BP) (systolic BP (SBP) of mm Hg or diastolic BP (DBP) of mm Hg) on incident cardiovascular disease (CVD) among middle-aged vs elderly population. We examined the risk of BP categories among 6273 participantsx30 years, free of CVD at baseline, during more than 9.3 years follow-up. Cox regression analysis was used to estimate the hazard ratio (HR) of CVD for normal BP group (SBP between mm Hg or DBP between mm Hg), high normal BP group and hypertension group (SBPX140 mm Hg or DBPX90 mm Hg or taking antihypertensive drugs), considering those with optimal BP (SBPo120 mm Hg and DBPo80 mm Hg) as reference. During follow-up, 512 CVD events occurred. There was significant interaction between age and BP categories (P ¼ 0.028) in prediction of CVD. In multivariate analysis, HRs (95% CIs) of CVD were 1.62 ( ) and 2.20 ( ) for middle aged with high normal and hypertensive BP groups, respectively. Among elderly (X60 years), HR was 2.09 ( ) only for hypertensive ones. High normal BP is a risk factor for incident of CVD only among middle-aged population. Furthermore, the effect of hypertension on incident CVD was stronger among younger population. Journal of Human Hypertension (2013) 27, ; doi: /jhh ; published online 5 January 2012 Keywords: prehypertension; cardiovascular disease; middle age; elderly INTRODUCTION It was first in 1939 that a study showed an association between a sharp increase in cardiovascular disease (CVD) mortality and blood pressure (BP) higher than 140/90 mm Hg. 1 Since then many prospective cohort studies have demonstrated a strong, graded and positive association between BP categories and risk of CVD. 2 In 2003,the Joint National Committee 7 (JNC7) from the United States introduced the concept of prehypertension into guidelines categorizing the individuals with systolic BP (SBP) between mm Hg or diastolic BP (DBP) between mm Hg as prehypertension groups. 3 However, the European guidelines divided this population into two groups; those with SBP between mm Hg or DBP between mm Hg are classified as normal, whereas those with SBP between mm Hg or DBP between mm Hg are classified as high normal. 4 Western and Japanese studies have shown that those with prehypertension are at higher risk of developing CVD compared with normotensive ones. 5,6 However, some other studies have found that prehypertension increased the rate of CVD only when accompanied with other risk factors. 7,8 Considering the different results about the effect of prehypertension on incident CVD, the role of ethnicity in assessment of CVD risk factors should be taken into consideration. Also the definition for preclinical stage of hypertension is still a matter of controversy. To best of our knowledge, there is no study documented on the association between BP categories and incidence of CVD in Middle Eastern populations where there is high prevalence of CVD and hypertension. 9,10 The aim of this study is to assess the independent risk of CVD according to BP categories among middle age and elderly populations in a Middle Eastern community-based cohort of the Tehran Lipid and Glucose Study (TLGS). METHODS Study population The TLGS, a prospective study aimed at determining the risk factors and outcomes for non-communicable disease was performing on a representative sample of residents of district-13 of Tehran, aged 3 years and over who were residence of district no. 13 of Tehran and were under the coverage of three medical health centers, were selected using multistage cluster random sampling method. Then, all the members of each family, including those not having risk factors, were invited for baseline measurements. 11,12 Subjects were categorized into the cohort and intervention groups, the latter to be educated for implementation of life style changes. From this group, 8071 subjects, aged X30 years were examined in a cross-sectional phase of TLGS (1999 to 2001), we excluded those with history of prior CVD (n ¼ 521). After that, those with missing data on SBP, DBP and all of the covariates were excluded, leaving 7010 subjects, of whom 6273 subjects (2694 males and 3579 females) were monitored until March 2009 for a median follow-up of 9.3 years (response rate: 6273/( ) E83.1%) (Figure 1). Written informed consent was obtained from all subjects, and the ethical committee of Research Institute for Endocrine Sciences approved this study. 1 Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran; 2 Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran and 3 Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran. Correspondence: Dr F Hadaegh, Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Science, PO Box , Tehran, Islamic Republic of Iran. fzhadaegh@endocrine.ac.ir Received 12 September 2011; revised 19 October 2011; accepted 7 November 2011; published online 5 January 2012

2 Figure participants aged 30 years (Baseline examination ) 7550 participants free from CVD at baseline 7010 participants with complete data 6273 were followed for median 9.3 years (End of follow up: March 2009) Study population. Clinical and laboratory measurements Excluded those with history of CVD at baseline (n=521) Exclude those with missing data on SBP, DBP and all of the other covariates (n=540) Exclude those who loss to follow up (n=737) At baseline, a trained interviewer collected information that included demographic data, medical history, family history of CVD, medication use and smoking habits using a validated questionnaire. Weight was measured, while subjects were minimally clothed without shoes, using digital scales (Seca 707, Seca Corp., Hanover, MA, USA; range kg) and recorded to the nearest 100 g. Height was measured in a standing position without shoes, using a stadiometer with shoulders in normal alignment. Body mass index (BMI) was calculated as weight (kg) divided by square of height (m 2 ). Using a standardized mercury sphygmomanometer (calibrated by the Iranian Institute of Standards and Industrial Researches) two measurements of SBP and DBP were taken on the right arm, after a 15- min rest in a sitting position and the mean of the two measurements was considered as subject s BP. From all study participants after h overnight fasting, a blood sample was drawn between 0700 and 0900 h. Plasma glucose was measured using an enzymatic colorimetric method with glucose oxidase. Total cholesterol (TC) was assayed using enzymatic colorimetric method with cholesterol esterase and cholesterol oxidase. All the blood analyses were done at the TLGS research laboratory on the day of blood collection using commercial kits (Pars Azmoon Inc., Tehran, Iran) and a Selectra 2 auto analyzer (Vital Scientific, Spankeren, the Netherlands). 11,12 CVD outcome Details of the collection of cardiovascular outcomes data have been published earlier. 13 To summarize, each participant was followed up annually for any medical event, by phone calls (at least one to the maximum of four calls with intervals of 1 week). A trained nurse asked them regarding any medical condition and then a trained physician collected complementary data about that event, during a home visit and by acquisition of data from medical files. The collected data were then evaluated by an outcome committee consisting of an internist, an endocrinologist, a cardiologist, an epidemiologist and other experts when needed, to assign a specific outcome for every event according to ICD-10 criteria 14 and American Heart Association classification for cardiovascular events. 15 The ischemic heart disease (ICD10 rubric I20-I25) and cerebrovascular diseases (ICD10 rubric I60-I69) were used to define CVD outcomes. In the current study, a diagnostic ECG and biomarkers were referred to as definite myocardial infarction. Probable myocardial infarction was also defined as positive ECG findings plus cardiac symptoms or signs plus missing biomarkers or positive ECG findings plus equivocal biomarkers. Stroke was classified as a new neurological deficit that lasted more than 24 h. Angiographically proven coronary heart disease (CHD) was confirmed by review of hospital records. The angiograms were defined as to the number of vessels involved (0, 1, 2 or 3) and to the severity of lesions, that is, greater or smaller than 50% lumen obstruction. For the purpose of this study any angiograms with more than 50% in at least one coronary artery was defined as angiographic proven CHD. 16 Unstable angina pectoris was defined by new cardiac symptoms or changing symptom patterns and positive ECG findings with normal biomarkers. Death from CHD or stroke was confirmed by reviewing by the death certificate and reconfirmation by medical records. Definition of terms Diabetes mellitus was defined as fasting plasma glucose (FPG) level X7 mmol l 1 and the current use of anti-diabetic drugs. Family history of premature CVD reflected any prior diagnosis of CVD in female first-degree relatives, aged less than 65 years or male first-degree relatives under the age of 55 years old. Smoking status was defined on the basis of response to the smoking behavior questions: those who have never smoked, former smokers and current smokers. According to 2007 European guidelines 4 for the management of arterial hypertension, we categorized subjects into four groups. The optimal BP group: those with SBP lower than 120 mm Hg and DBP lower than 80 mm Hg; the normal BP group: those with BP between 120 and 129 mm Hg or DBP between 80 and 84 mm Hg; the high normal BP group: those with SBP between 130 and 139 mm Hg or DBP between 85 and 89 mm Hg; and the hypertensive group: those with SBP higher than 140 mm Hg or DBP higher than 90 mm Hg or taking antihypertensive medications. If systolic and diastolic pressures fell into different categories, participants were assigned to the higher category. Since there is no standard age to distinguish middle age from elder population, but age 60 years is the most frequently used guideline in studies, 17 we stratified the study population by age into two groups: middle aged (30pageo60) and elderly (agex60). Statistical analysis Baseline characteristics including age, SBP, DBP, TC, BMI, intervention, lipid drug, diabetes, smoking behavior and family history of CVD were expressed in mean (standard deviation) and frequency (percentage) for continuous and categorical variables. Comparisons between groups were made by ANOVA test for continuous variables and w 2 test for categorical variables. Interactions between BP classifications and age categories and sex with incident CVD were tested by log-likelihood ratio test, in multivariate analysis. Since we had no interaction between BP groups and sex, we performed our analysis in a pooled population. We found a significant interaction, however, between age groups (that is, middle-aged and elder group) and BP categories (P ¼ for high normal BP and P ¼ for hypertensive group) regarding CVD/CHD events; hence, the analysis was performed separately among middle-aged and elder group. Cox regression analysis was used to estimate the hazard ratios (HR) of CVD and CHD events for normal BP, high normal and hypertensive groups, given the optimal group as the reference in middle-aged and elderly subjects separately. We did adjustment for age as continuous variable in different age groups, sex, TC, BMI, lipid drug, diabetes, smoking and family history of premature CVD as the main confounders. Follow-up duration was defined as the period between entrance to study and the end point in each analysis. End points were considered as the first CVD or CHD events and censoring was defined as leaving the residence area, non-cvd death, lost to follow-up or until the end of follow-up. The proportional hazards assumption in the Cox model was checked graphically and with the 19

3 20 Schoenfeld residual test. 18 All proportionality assumptions were generally appropriate. A P-valueo0.05 was considered significant. Statistical analyses were performed using SPSS version 15 and STATA version 10.0 (Stata Corp. LP, College Station, TX, USA). RESULTS There was no difference in the baseline characteristics of participants versus non-participants; however, the included individuals (n ¼ 6273) had lower prevalence of smoking (14.4 vs 19.6%, P ¼ 0.00) and diabetes (9.5 vs 14.3%, P ¼ 0.00) than nonparticipants (n ¼ 1277). The study sample consisted of 6273 subjects (5064 middle age and 1209 elderly with mean ages 42.5 and 66.3, respectively) and prehypertension (normal and high normal BP) was observed in 34.5%of the population. Table 1 shows the baseline characteristics of participants according to BP categories. Generally, participants with hypertensive BP were older, had higher TC, BMI and higher rates of lipid drug use, in both the middle aged and elderly; family history of premature CVD and diabetes were more common among these. Also the hypertensive group tended to be nonsmokers. Only for intervention, differences between the groups were not meaningful. During 9.3 years of follow-up, 512 CVD (444 CHD) events occurred. The incidence rate of CVD was 6.2 and 24.7 per 1000 person-years for the middle aged and elderly, respectively. The mean (s.d.) and prevalence of baseline characteristics according to CVD outcomes are given in Table 2. In both the middle aged and elderly, when compared with those who had no CVD events, those who did had higher SBP and DBP; also, diabetes and smoking were more common in this group. Age and multivariable models were used to estimate the HR for cardiovascular events according to BP categories; results are shown in Table 3. In the age-adjusted model, HRs (95% CIs) of CVD events were 1.75 ( ), 2.38 ( ) for the middle aged with high normal and hypertensive BP, respectively; those with normal BP did not have higher risk for incident CVD compared with those in optimal group. In the elderly, HRs of CVD incidence were 1.77 ( ) for hypertensive population and other groups did not have higher risks of developing CVD than the optimal group. In multivariable adjusted model, HRs (95% CIs) of CVD were 1.62 ( ) and 2.20 ( ) for the middle aged with high normal and hypertensive BP, respectively. In elderly participants, the HR was 2.09 ( ) for hypertensive ones. Overall, after further adjustment for other risk factors, the HRs decreased but were still significant. Among elderly participants, the ones with prehypertension (normal and high normal BP ones) did not have a higher risk for CVD. Similar results were achieved for CHD events in age and multivariate adjusted analysis. However, among elderly Table 1. Baseline characteristics of study subjects according to blood pressure category Variable Blood pressure category P-value Optimal Normal High normal Hypertensive Middle aged (30pageo60 years) No. of subjects Male/female 974/ / / / Age, years 40.2 (7.7) 42.0 (8.2) 44.4 (8.4) 47.6 (7.7) SBP, mm Hg (7.8) (6.9) (8.2) (18.3) DBP, mm Hg 70.5 (5.7) 79.6 (4.2) 84.8 (4.2) 92.3 (9.3) TC, mmol l (1.1) 5.5 (1.1) 5.7 (1.1) 5.9 (1.3) Body mass index, kg m (4.1) 28.0 (4.3) 28.3 (4.3) 29.9 (4.7) Intervention (%) Lipid drug (%) Diabetes (%) Smoking Current smokers (%) Past smokers (%) Non-smokers (%) FH premature CVD (%) Elderly (agex60 years) No. of subjects Male/female 130/66 105/90 103/78 281/ Age, years 65.8 (5.2) 65.6 (4.5) 66.5 (5.1) 66.6 (5.4) SBP, mm Hg (7.4) (4.8) (5.6) (19.7) DBP, mm Hg 67.7 (6.6) 75.8 (6.7) 78.5 (7.4) 87.6 (11.7) TC, mmol l (1.1) 5.8 (1.2) 5.7 (1.1) 6.1 (1.2) Body mass index, kg m (4.1) 26.6 (3.9) 27.0 (3.6) 28.3 (4.5) Intervention (%) Lipid drug (%) Diabetes (%) Smoking Current smokers (%) Past smokers (%) Non-smokers (%) FH premature CVD (%) Abbreviations: CVD, cardiovascular disease; DBP, diastolic blood pressure; FH, family history; SBP, systolic blood pressure; TC, total cholesterol. Mean±s.d. are shown for continuous variables and % for categorical variables. Comparisons between groups were done with ANOVA test and w 2. Difference among categories was significant (Po0.05 according to ANOVA or w 2 test). Middle aged: 30pageo60, elderly: agex60.

4 Table 2. Baseline characteristics of study subjects according to outcome category Groups and variables Outcome category P-value Non-CVD event CVD events Middle aged (30pageo60 years) No. of subjects Male/female 1925/ / Age, years 42.1 (8.3) 49.5 (7.1) SBP, mm Hg (16.1) (22.6) DBP, mm Hg 78.3 (10.2) 84.1 (13.2) TC, mmol l (1.1) 6.2 (1.3) Body mass index, kg m (4.5) 28.7 (4.7) Intervention (%) Lipid drug (%) Diabetes (%) Smoking Current smokers (%) Past smokers (%) Non-smokers (%) FH premature CVD (%) Elderly (agex60 years) No. of subjects Male/female (476/496) (143/94) Age, years 66.2 (5.2) 66.7 (5.3) SBP, mm Hg (22.0) (24.1) DBP, mm Hg 80.4 (11.9) 84.0 (13.5) TC, mmol l (1.2) 6.0 (1.3) Body mass index, kg m (4.5) 27.4 (4.2) Intervention (%) Lipid drug (%) Diabetes (%) Smoking Current smokers (%) Past smokers (%) Non-smokers (%) FH premature CVD (%) Abbreviations: CVD, cardiovascular disease; DBP, diastolic blood pressure; FH, family history; SBP, systolic blood pressure; TC, total cholesterol. Mean±s.d. are shown for continuous variables and % for categorical variables. Comparisons between groups were done with ANOVA test and w 2. Difference among categories was significant (Po0.05 according to ANOVA or w 2 test); Middle aged: 30pageo60, elderly: agex60. participants, the hypertensive group had a marginally significant risk of getting CHD compared with the optimal group (HR: 1.52 ( ), P-value: 0.054) in age-adjusted analysis. During follow-up, we had 78 cases of stroke (23 and 55 cases of stroke among middle-aged and elderly people, respectively). In both age and multivariable adjusted analysis, high normal BP and hypertension did not remain as a predictor of incident stroke among middle-aged group. Among elder ones, however, hypertension remained as an independent predictor of incident stroke (HR: 7.3, CI: , P-value ¼ 0.007). Additionally among elder population, high normal BP highlighted a marginally significant risk for prediction of incident stroke in both age and multivariate adjusted analysis (multivariate adjusted HR: 4.1, CI: , P-value ¼ 0.07). DISCUSSION During more than 9 years follow-up of a Middle Eastern population, we showed that the effect of BP categories on CVD event differs as age increased. Despite higher incidence rate of CVD among the elderly, high normal BP was independently associated with an increased risk of CVD only in the middle-aged population. Furthermore, after controlling for CVD risk factors, hypertension increased the risk of developing CVD events in both age categories, but this risk was higher in the middle aged as compared with the elderly. The result of current study shows that the overall prevalence of prehypertension (normal and high normal BP) was 34.5%. The corresponding prehypertension prevalence ranged from 47% in China, 31% in the United States, 34% in Taiwan and 40% in Ghana Except for the prevalence in china, these amounts were generally similar to our estimates, indicating that prevalence of prehypertension is high in both developed and developing countries. In recent decades much attention has been given treating disease in preclinical stages, but the concept of prehypertension as a preclinical stage, introduced by JNC7 in is still a matter of controversy. Consistent with some other studies, 23,24 this study indicated that compared with those with optimal BP group, persons categorized as high normal BP were more likely to develop CVD. But those with normal BP did not have any higher risk of developing CVD. Among participants of Women s Health Initiative, however, those with normal BP at baseline had a 40% higher risk for developing CVD events compared with those with optimal BP at baseline. 25 JNC 7 combined these two categories (normal and high normal BP) together as prehypertension, however, due to large differences in cardiovascular risk between these categories and probably need of different kind of treatment strategies toward these categories, separating them seemed to be more reasonable. So, in light with our findings, we agreed with European guidelines that reflect these risk distribution more precisely (that is, normal and high normal BP). 4 On the other hand, several studies have demonstrated a strong, direct, graded and continuous association between BP categories and risk of CVD down into the range of normal BP. The Prospective Studies Collaboration Meta-analysis showed that for each 20 mm Hg increase in SBP or 10 mm Hg in DBP over 115/75 mm Hg, there was twofold increase in risk of CVD mortality. 2 Using multivariate analysis, we recently demonstrated that for each 18 mm Hg increase in SBP, there was 35% increase in risk of CVD mortality, without defining a threshold value of SBP. 26 In line with Vasan et al. 24 in our study, gender did not modify the risk of developing CVD in prehypertensive participants. In a Japanese urban cohort, however, only for men significant risk was found with high normal BP. 6 Comparing the middle aged and elderly with hypertension demonstrated that our middle-aged population is more likely to develop CVD than are the elderly (HR 2.38 vs 1.77 in age adjusted model); additionally, high normal BP remained as an independent predictor only among the younger population. In the Framingham Heart study, the 10 years cumulative incidence of CVD among an elderly population with high normal BP was significantly higher than the younger ones; however, they did not report the multivariate HR in different age groups. 24 Furthermore, in line with our findings, among a Chinese population, prehypertension highlighted higher risk among middle-aged group as compared with the elderly. 27 The lower risk reported for the elderly in getting CVD compared with the middle-aged group in our study can be interpreted in many ways. The first reason could be related to treatment by anti-hypertensive drugs; the elderly took more antihypertensive drugs than the younger population (41.6 vs 25.1%) and the high probability of receiving anti-hypertensive medications during follow-up might decrease the risk of CVD events, as suggested by others. 28,29 The second reason could be attributed to the coexistence of more other comorbidities in the elderly resulting in reduced risk of hypertension and prehypertension for CVD events. Systolic Hypertension in the Elderly Program (SHEP) clinical trial 30 has introduced a paradigm shift for treatment of hypertension in the elderly, showing that increasing BP with advancing age is not harmful as long as it remains asymptomatic. The current study highlighted that an older population with hypertension had generally higher risk for incident CVD rather than CHD events (multivariate HR 2.09 vs 1.63, respectively), as 21

5 22 Table 3. Age- and multivariable-adjusted HRs for CVD (CHD) according to blood pressure category Groups and variables Blood pressure category Optimal Normal High normal Hypertensive Middle aged (30pageo60 years) Cardiovascular disease Case Age-adjusted ( ) 1.75 ( ) 2.38 ( ) P-value Multivariable-adjusted ( ) 1.62 ( ) 2.20 ( ) P-value Coronary heart disease Case Age-adjusted ( ) 1.87 ( ) 2.49 ( ) P-value Multivariable-adjusted ( ) 1.71 ( ) 2.28 ( ) P-value Elderly (agex60 years) Cardiovascular disease Case Age-adjusted ( ) 0.85 ( ) 1.77 ( ) P-value Multivariable-adjusted ( ) 0.89 ( ) ( ) P-value Coronary heart disease Case Age-adjusted ( ) 0.63 ( ) 1.52 ( ) P-value Multivariable-adjusted ( ) 0.64 ( ) 1.63 ( ) P-value Abbreviations: CHD, coronary heart disease; CVD, cardiovascular disease; HR, hazard ratio. Multivariable models were adjusted for age, sex, total cholesterol, body mass index, smoking behavior, diabetes, lipid-lowering drug use and family history of premature CVD. Middle aged: 30pageo60, elderly: agex60. shown previously among general population in different studies. 23,25,27 In a younger population, however, we did not find any difference in risk between the high normal BP and hypertensive groups regarding CHD or CVD events. In our study hypertension was found as an independent risk of incident stroke only among elder population, probably due to very limited number of stroke events among younger ones. The INTERSTROKE study, however, showed that hypertension (as defined by self-reported hypertension or BP 4160/90 mm Hg), was more strongly associated with stroke in individuals younger than 45 years than in those aged 45 years or older. 31 Our study had several limitations. First, two BP measures were obtained on a single visit, which might result in underestimation of the strength of the relation between high-normal BP and the incidence of CVD. 32,33 Furthermore, Rothwell et al. 34 recently highlighted the variability and instability in SBP have important roles in prediction of vascular events independent of mean SBP (that is, themaximumsbpismorepredictivethanismeansbp)anddraws attention to clinical implications and future research. Second, the participants had lower prevalence of diabetes and cigarette smoking leading to underestimation of CVD incidence in the current study; however, the percentage of non-followed population was not different among BP categories (9-11% in each category, P ¼ 0.12), which induces a non-differential selection bias. Third, some important risk factors for CVD such as diet were not measured. Nutrition is important but can be very difficult to measure with adequate precision. Fourth, we did not consider changes in different BP groups during follow-up. However, Vasan et al. 24 highlighted that considering these changes in BP categories during follow-up, high normal BP still remained as an independent risk factor for CVD events. Finally, it must be emphasized that the findings of this study were determined in Middle East Caucasian residents in the capital city of Iran and further studies should be conducted to determine whether our findings are applicable to other populations of this region. Nonetheless, our study has its strengths in having a large representative sample of Iranian urban population with very reliable surveillance for CVD events. Furthermore, we used actual measurements of variables rather than self-reported data, and several CVD risk factors were taken into account in our data analyses. CONCLUSIONS High normal BP is a risk factor for incident CVD only among middle-aged Iranian populations. Furthermore, the effect of hypertension on incident CVD was stronger among younger individuals. Clinical research needs to determine whether lowering high normal BP can reduce the risk of CVD among younger population. What is known about this topic Western and Japanese studies have shown that those with prehypertension are at higher risk of developing cardiovascular disease compared with normotensive ones. Others have found that prehypertension increased the rate of CVD only when accompanied with other risk factors. What this Study adds Among Middle East populations, high normal blood pressure was independently associated with an increased risk of cardiovascular and coronary heart disease only in the middle aged, but not in elder ones. Hypertension increased the risk of developing cardiovascular and coronary heart disease in both age categories, but this risk was higher in the middle aged as compared to the elderly.

6 CONFLICT OF INTEREST The authors declare no conflict of interest. ACKNOWLEDGEMENTS This study was supported by Grant No.121 from the National Research Council of the Islamic Republic of Iran. We express appreciation to the participants of district 13, Tehran, for their enthusiastic support in this study. We would like to thank Ms N Shiva for the English editing of manuscript. REFERENCES 1 Robinson SC, Brucer M. Range of normal blood pressure: a statistical and clinical study of 11,383 persons. Arch Intern Med 1939; 64(3): Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360(9349): Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. 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