Published online before print June 5, 2006, doi: 10.1161/01.HYP.0000227507.69230.fc
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(Hypertension. 2006;48:254.)
© 2006 American Heart Association, Inc.
Original Articles |
Prevalence of Prehypertension and Associated Cardiovascular Risk Profiles Among Young Israeli Adults
From the Department of Epidemiology (I.G.), Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Hypertension Unit, C. Sheba Medical Center and Periodic Examination Center (E.G., Y.S.) and Army Health Branch (M.H.), IDF Medical Corps, Tel Hashomer, Israel (affiliated with Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel).
Correspondence to Yehonaytan Sharabi, Hypertension Unit, C. Sheba Medical Center, Tel Hashomer, 52621, Israel. E-mail sharabiy{at}sheba.health.gov.il
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Abstract |
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Recently the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure introduced the term "prehypertension" for systolic blood pressure levels of 120 to 139 mm Hg and diastolic BP levels of 80 to 89 mm Hg. Little is known about the prevalence of this entity and the cardiovascular risk factors associated with it. We aimed to determine the prevalence of prehypertension and the cardiovascular risk factors associated with it in a large population-based sample of young Israeli adults. We studied 36 424 Israel Defense Forces employees during the years 1991 to 1999. Subjects completed a detailed questionnaire and underwent physical examination, and blood samples were drawn after a 14-hour fast. Prehypertension was defined as a systolic blood pressure of 120 to 139 mm Hg, and/or a diastolic blood pressure of 80 to 89 mm Hg. We calculated the age- and sex-specific prevalence of prehypertension and other cardiovascular risk factors associated with this condition. Prehypertension was observed among 50.6% of men and 35.9% of women. The prehypertensive group had higher levels of blood glucose, total cholesterol, low-density lipoprotein cholesterol, and triglycerides, higher body mass index, and lower levels of high-density lipoprotein cholesterol than did the normotensive group. Multivariate logistic regression analysis showed that body mass index was the strongest predictor of prehypertension among both males and females (odds ratio, 1.100; 95% CI, 1.078 to 1.122 and odds ratio, 1.152; 95% CI, 1.097 to 1.21, respectively, for every 1 kg/m2 increase). Our findings support the recommendation of lifestyle modification for prehypertensive patients. Further prospective studies are required to determine the role of pharmacotherapy in prehypertension.
Key Words: cardiovascular diseases • young adults • hypertension, borderline
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Introduction |
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Hypertension is likely the most common disease on Earth.1 It is associated with an increased risk of morbidity and mortality from cardiovascular disease (CVD) and represents the single greatest preventable cause of death in humans. The standard definition of hypertension as blood pressure (BP)
140/90 mm Hg is based on the observation that the risk of CVD increases sharply above this level. However, recent data have shown that an increased risk of CVD is present in persons with BP levels as low as 115/70 mm Hg and that this risk increases steadily with rising BP.2 The incremental association between BP and CVD risk has been reflected recently in the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7).3 In its report, the JNC7 introduced a new BP category, "prehypertension," defined as a systolic BP (SBP) of 120 to 139 mm Hg and/or a diastolic BP (DBP) of 80 to 89 mm Hg. Since the publication of the JNC7 report, several studies have assessed the prevalence and significance of prehypertension. Still, the importance of this entity in regard to global CVD risk and the preferred approach to its treatment are still a matter of debate, and the term prehypertension has yet to be widely adopted.
Evidence supporting a prehypertensive state has been demonstrated in several studies,4–11 chief among them the longitudinal Framingham Heart Study, which showed that BP in the prehypertensive range preceded the diagnosis of hypertension in 90% of subjects aged 55 years.12 In another longitudinal study, Winegarden11 showed that, relative to normotensive subjects, the risk of hypertension was substantially higher among subjects with "high normal" BP (130 to 139/85 to 89 mm Hg). However, whereas several reports have documented an increased risk of CVD among prehypertensive subjects,5,6,8,12,13 others suggest that prehypertension increases the risk of CVD only modestly or that this risk increases only when prehypertension is associated with additional risk factors.4,7
Data on prehypertension in young adults are lacking, and little is known on the risk factors for prehypertension and their association with other CVD risk factors. It is presently unclear whether the increased risk of CVD among prehypertensive subjects is wholly related to increased BP or whether it can be attributed to a deleterious CVD risk factor profile. The purpose of this study was to determine the prevalence of prehypertension among the young Israeli adult population and to characterize the CVD risk profiles and CVD risk scores of prehypertensive subjects within this population.
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Methods |
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Study Population
The Israel Defense Force (IDF) employs career service personnel in a wide array of occupations, ranging from highly educated professionals and trained technicians to skilled and unskilled workers. Personnel education levels vary widely, and occupational environments include white-collar office-based surroundings, blue-collar factory-like conditions, and unskilled field-based laboring conditions. Most career personnel enter the IDF workforce at the age of 21 and end their service at the compulsory military retirement age of 50. The workforce includes both combatants and noncombatants, but the proportion of combatants is small. All career employees are required to undergo periodic medical examination, which includes a thorough medical history, physical examination, and laboratory tests. We analyzed the periodic examination data of subjects aged 20 to 50. This group represents the overall Israeli working population and provides a basis for comparison with data collected previously in Israel and elsewhere.
Data Collection
Between January 1991 and December 1999, 36 424 healthy subjects (32 024 males and 4400 females) underwent periodic medical evaluation. Subjects were examined at 3- to 5-year intervals starting at the age of 20 and were summoned automatically for examination by our computerized queuing system. Compliance with examination was high, and 93% of the summoned population presented at the testing center and underwent testing. Subjects completed a detailed medical questionnaire, which included items on smoking habits and physical activity. Questions regarding physical activity included the following: whether the subject performed any physical activity on a regular basis, the type of activity performed, and the weekly frequency of the activity. Physical activity was defined in the questionnaire as an aerobic activity of >30 minutes’ duration. The questionnaire listed examples (walking, cycling, jogging, etc) for the purpose of clarity. Blood samples were drawn after a 14-hour fast and were analyzed for levels of glucose, triglycerides, total cholesterol, and, from 1996, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. Total cholesterol was measured by means of oxidation and peroxidation reactions, and LDL cholesterol was calculated using the Freidewald formula.
SBP and DBP were measured according to American Heart Association guidelines using a mercury column sphygmomanometer and a cuff suitable to the subject’s arm circumference. BP was measured twice by skilled, trained physicians after 5 minutes of rest in the sitting position, and the average of the measurements was recorded. Physical examination included measurement of height (centimeters) and weight (kilograms), and a resting 12-lead ECG was recorded. Results were entered into the computerized Young Adult Periodic Examinations in Israel (YAPEIS) database.14 For subjects examined more than once, results of the latest examination were used for analysis.
Data Analysis
We analyzed the physical, metabolic, and lifestyle parameters of our subjects. Physical parameters included body mass index (BMI) and BP. BMI was calculated by dividing weight (in kilograms) by the square of the height (in meters). Subjects were defined as overweight and obese when BMI was 25 to 29.99 and 30 kg/m2, respectively. Normotension was defined as SBP <120 mm Hg and DBP <80 mm Hg. Prehypertension was defined as SBP 120 to 139 mm Hg and/or DBP 80 to 89 mm Hg. We further divided the prehypertension group into 2 categories15,16: "low prehypertension" (SBP, 120 to 129 mm Hg and/or DBP, 80 to 84 mm Hg) and "high prehypertension" (SBP, 130 to 139 mm Hg and/or DBP, 85 to 89 mm Hg). Hypertension was defined as SBP 140 mm Hg and/or DBP 90 mm Hg or by the use of antihypertensive medications.
Metabolic parameters included fasting glucose, triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. Subjects were considered hyperglycemic if their fasting blood glucose level was 126 mg/dL or if they used hypoglycemic medications. Subjects were considered hypercholesterolemic if their total cholesterol was 200 mg/dL or if they used lipid-lowering medication. A high LDL cholesterol level was defined as a concentration >129 mg/dL.
Lifestyle parameters included cigarette smoking and physical activity habits. The reported number of cigarettes smoked per day was recorded, and subjects were defined as smokers if they smoked 1 cigarette per day. Sedentary lifestyle was defined by the routine performance of <1 physical activity per week.
Because we did not measure waist circumference, we modified the National Cholesterol Education Programme (NCEP) criteria for the definition of the metabolic syndrome and used BMI 25 kg/m2 as a substitute criterion for waist circumference. Metabolic syndrome was, therefore, defined by the presence of 3 of the following criteria: fasting blood glucose level of 110 to 125 mg/dL; triglyceride level 150 mg/dL; HDL cholesterol 
40 mg/dL for men or 50 mg/dL for women; BMI 25 kg/m2; and SBP 130 mm Hg or DBP 85 mm Hg.17 The Framingham–Anderson Heart Study Coronary Heart Disease prediction model was used to define the probability of developing coronary heart disease within the next 10 years.18 The calculation, which was sex stratified, took into account the status of 7 risk factors: age, total cholesterol level, HDL cholesterol level, SBP, smoking status, and the presence or absence of diabetes mellitus and left ventricular hypertrophy. This calculation was completed only for data collected after 1996, because HDL cholesterol was not routinely tested before this time.
We calculated the prevalence of normotension, prehypertension, and hypertension among males and females in 3 age groups: 21 to 30 years, 31 to 40 years, and 41 to 50 years. Differences in the means and prevalence of study variables between the prehypertensive group and the 2 remaining BP groups, as well as between the low and high prehypertension groups, were compared using Student t tests for continuous variables and 
2 tests for categorical variables. Comparisons between men and women in each BP group were carried out using Student t test. For each BP group, we also calculated the sex-specific prevalence of hyperglycemia, hypercholesterolemia, high LDL cholesterol, overweight, obesity, metabolic syndrome, smoking, and sedentary lifestyle and calculated the proportion of subjects with a >15% risk of developing coronary heart disease within the following 10 years. Logistic regression analyses were used to test significant determinants of prehypertension status, with prehypertension serving as the dichotomous outcome variable (prehypertension versus normal hypertension) and age, sex, presence of metabolic syndrome, lifestyle parameters, and BMI as the independent predictor variables. Backward selection was used as the method for variable selection, and variables with P>0.05 were eliminated from the model. Data were analyzed using SPSS software (version 12.0; SPSS Inc, Chicago, Ill).
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Results |
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Prehypertension was observed in 48.9% (50.6% among men, 35.9% among women) of the subjects. The prevalence of prehypertension remained constant across age groups among men but increased with age among women (Figure; P for trend in females <0.001). The overall prevalence of hypertension was 19.1% (20.4% among men, 9.8% among women).
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When compared with the normal BP group, the prehypertensive group was older; had higher levels of blood glucose, total cholesterol, LDL cholesterol, triglycerides, and BMI; and had lower levels of HDL cholesterol (Table 1). Prehypertensive subjects were more likely than normotensive subjects to be smokers but less likely to maintain a sedentary lifestyle. Similar but more pronounced differences were apparent in the comparison between the hypertensive and normotensive groups, although fewer hypertensive subjects than normotensive subjects reported smoking (Table 1).
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In all of the BP groups, men were younger than women and had higher mean blood glucose, LDL cholesterol, and triglyceride levels and lower mean HDL cholesterol levels (Table 2). Normotensive and prehypertensive men had higher BMI values than women.
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The prevalence of cardiovascular risk factors was significantly higher in the prehypertension group than in the normotensive group (Table 3). Fewer prehypertensive men reported a sedentary lifestyle than did normotensive men. The prevalence of CVD risk factors was highest among hypertensive subjects, but in this group the prevalence of smoking and sedentary lifestyle was also the lowest. The risk of developing CVD within 10 years, as predicted by the Framingham–Anderson Heart Study Coronary Heart Disease model, was >15% for 8.5%, 19.7%, and 43.1% of normotensive, prehypertensive, and hypertensive men and 0.4%, 3.2%, and 12.6% of women, respectively (Table 3).
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Multivariate logistic regression analysis showed that male gender was the most powerful predictor of prehypertension, with an odds ratio (OR) of 1.930 (95% CI, 1.614 to 2.308). BMI was the strongest modifiable predictor of prehypertension among both men and women (OR, 1.100; 95% CI, 1.078 to 1.122; and OR, 1.152; 95% CI, 1.097 to 1.210, respectively; Table 4). The risk of prehypertension was lower among smokers (Table 4). Within the prehypertension group there was an increment in the risk profile (Table 5). Subjects in the high range of prehypertension were older; had higher levels of blood glucose, total cholesterol, LDL cholesterol, triglycerides, and BMI; had lower levels of HDL; and were more likely to be smokers, as compared with subjects in the low range of prehypertension.
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Discussion |
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The significance of the prehypertension category in the JNC7 report is a matter of controversy. The term was established after the results of longitudinal studies of subjects >55 years of age, which suggested that subjects with BP 120 to 139/80 to 89 mm Hg are at risk for developing hypertension. Moreover, some reports indicated that these subjects are at a greater risk of CVD. Our survey is the first that is based on a standardized and comprehensive medical evaluation of a large young population. We observed Israeli adults between the ages 25 and 45, assessed the prevalence of prehypertension in this population, identified determinants of prehypertension, characterized the CVD risk factor profile of prehypertensive subjects, and calculated the risk among prehypertensive subjects for developing future CVD. Our results show that prehypertension is very common among young adults, that men are affected more often than women at this age, and that the rate in women increases with age. We also found that obesity had the strongest association with prehypertension. Furthermore, the global CVD risk profile among prehypertensive subjects, as manifested by the Framingham risk score, shows that prehypertensive subjects carry more than double the risk of a future CVD event than do normotensive subjects. This is most likely because of the fact that prehypertension is associated with a higher prevalence of the additional CVD risk factors, which collectively result in a risk-heavy profile. This finding probably explains the increased rate of CVD events observed among prehypertensive subjects.5,6,13
The prevalence of prehypertension in our study was higher than that found in National Health and Nutrition Examination Survey (NHANES) data derived from 4805 adults studied between 1999 and 2000.19 In that cross-sectional analysis, prehypertension was found in 31% of the cohort. Similar to our findings, men were affected more often than women (40% versus 23%). A similar rate was found in a survey in Taiwan, where 34% of the adult population was found to be prehypertensive.20 Our findings reinforce these smaller-scale studies. The minor differences observed between studies might be attributable to variations in methodology and population characteristics, because ethnic differences have been shown to play a role in the in the prevalence of prehypertension.21 Our results show that prehypertension is associated with an increased prevalence of other CVD risk factors. Similarly, a further analysis of the NHANES database on a small population sample supports our findings.5 Furthermore, a study of 506 Japanese subjects found that the prevalence of the metabolic syndrome among prehypertensive subjects was higher than that among normotensive subjects but lower than among hypertensive subjects.22 These results are consistent with our findings.
Obesity was found to be a major determinant of prehypertension even after controlling for other risks, such as age and sedentary lifestyle. Similar findings were found in the NHANES report and in the Taiwanese survey.19 The association between BP and weight is strong and linear, even in the normal range of BP and BMI.23 Therefore, it follows that weight should be a major determinant of prehypertension.
The link among prehypertension, CVD risk factors, and the increased risk of CVD morbidity and mortality may be explained by the proinflammatory nature of prehypertension and the association of this condition with increased C reactive protein levels,24 tumor necrosis factor 
, amyloid A, and homocysteine.25 Moreover, endothelial dysfunction is known to be prevalent at the high end of the normotension spectrum.26 Thus, endothelial dysfunction and a generalized inflammatory state, coupled with a high prevalence of CVD risk factors, together provide a likely explanation for the increased rate of CVD events among prehypertensive subjects.
It is well established that hypertension should be controlled and, when possible, prevented. Some question remains, however, as to the appropriate therapeutic approach to prehypertension. Over the last decade, attention has been drawn to the diagnosis and treatment of disease during the preclinical stages, before the progression to overt clinical manifestations. The true question regarding prehypertension is not the mere method of its progression to overt hypertension but rather the global CVD risk associated with this condition and the potential risk reduction to be gained by early initiation of treatment. A simulation model has shown that elimination of prehypertension results in a substantial public health benefit, thus providing the rationale for an interventional approach to this condition.27 It is important to note that prehypertension, per se, is not associated with an increased risk of CVD, unless accompanied by additional risk factors.7 However, <10% of prehypertensive subjects have this condition alone. Accordingly, subjects with prehypertension are at risk for CVD events, and a global risk reduction is indicated. Current guidelines recommend lifestyle modifications alone, because no studies have evaluated the efficacy of pharmacological interventions on prehypertension. Ongoing studies of thioglitazone in prediabetic patients and statins in patients with LDL <130 mg/dL might encourage similar trials in prehypertension. That said, we believe that the increased prevalence of obesity and sedentary lifestyle observed today would make behavioral changes the most logical and effective choice for modifying the natural history of prehypertension and its progression to overt hypertension.
Our study has several limitations. First, we conducted a cross-sectional study, and the prevalence of the various BP categories is based on single BP measurement. Nevertheless, other reports of the same nature, such as the NHANES, used similar methodology, making it suitable for purposes of comparison. Second, we used BMI 25 kg/m2 as a marker of obesity in place of waist circumference, as described previously.17 Finally, all of the subjects included in this study were IDF employees, which may limit the external validity of the findings.
In conclusion, the association between BP and CVD risk is notable even when BP levels are <140/90 mm Hg. Prehypertension is a risk factor for overt hypertension, and several small-scale studies have demonstrated its association with increased CVD morbidity. Our study shows that this condition is very common among young adults and is associated with a poor CVD risk factor profile. Collectively, prehypertension doubles the risk for future CVD events. Currently there are no clinical studies on specific interventions to regress prehypertension or prevent its progression to hypertension. However, current JNC7 recommendations indicate lifestyle modification for prehypertensive patients. Our findings, mainly that obesity is a major determinant of prehypertension and that a lack of physical activity is common in these patients, indicate that such an approach would probably be the most effective strategy. This recommendation, however, remains to be validated in a clinical study, as does the need for antihypertensive therapy in high-risk prehypertensive patients.
Perspectives
Our study demonstrates that among a large group of young, healthy, working adults, prehypertension is prevalent and is associated with multiple cardiovascular risk factors. These results further underline the need for routine BP measurements in young adults to identify subjects with prehypertension who should be the target of lifestyle modification. Further studies should be designed to assess the role of prehypertension as an independent cardiovascular risk factor and to assess the effect of lifestyle modification and therapeutic interventions on the progression to hypertension, as well as on cardiovascular morbidity and mortality.
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Acknowledgments |
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Disclosures
None.
Received February 12, 2006; first decision February 23, 2006; accepted May 8, 2006.
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