(23) 17, 535 54 & 23 Nature Publishing Group All rights reserved 95-924/3 $25. www.nature.com/jhh ORIGINAL ARTICLE Increased variance in blood pressure distribution and changing hypertension prevalence in an urban Indian population R Gupta 1, AK Sharma 1, VP Gupta 2, S Bhatnagar 2, S Rastogi 3 and PC Deedwania 4 1 Monilek Hospital and Research Centre, Jaipur, India; 2 Department of Statistics, University of Rajasthan, Jaipur, India; 3 Department of Food and Nutrition, University of Rajasthan, Jaipur, India; 4 University of California San Francisco-VA Medical Center, Fresno, CA, USA The objective of the study was to determine trends in age-specific blood pressure (BP) distribution and hypertension prevalence in an urban Indian population. In successive hypertension epidemiological studies (1995 and 22), randomly selected 2212 subjects (1412 men, 797 women) in the first and 1123 subjects (55 men, 573 women) in the second study were evaluated. BP was measured using World Health Organization guidelines and hypertension diagnosed using the American Joint National Committee-VI report. Age-specific BP levels in the first and the second study were determined and compared. The mean values of systolic and diastolic BP were not significantly different in various age groups in the first and the second studies. There was an increased variance in the second study as denoted by the significant increase in standard deviations and coefficients of variation in systolic as well as diastolic BP levels at age groups X5 years in men and X4 years in women (Po.5). The age-adjusted prevalence of hypertension (known or BP X14/X9 mmhg) in the first study was 29.5% (men) and 33.5% (women), and in the second study was 3.% (men) and 3.3% (women) (P ¼ NS). In the second as compared to the first study, there was decrease in age-adjusted prevalence of stage I hypertension (men 16.8 vs 24.9%, women 15.4 vs 27.5%), and increase in stage II hypertension (men 11.7 vs 2.8%, women 18.8 vs 3.1%), and combined stage II and III hypertension (men 13.5 vs 4.7%, women 16.7 vs 6.%) (Po.1). This change was associated with greater prevalence of obesity in the second study. In conclusion, increased systolic and diastolic BP dispersion over a 7-year period in this urban population is associated with unchanged hypertension prevalence, decline in stage I hypertension and upsurge in more severe grades. Increasing environmental factors, particularly obesity, appear important. (23) 17, 535 54. doi:1.138/sj.jhh.11588 Keywords: epidemiology; risk factors; environmental factors Introduction Hypertension has emerged as a major public health problem in India and many developing countries. 1 There is sufficient clinical and epidemiological evidence that hypertension is increasing in India. It has been reported that hypertension prevalence in India quadrupled in urban as well as rural populations over a 5-year period from early 195s to late 199s. 2,3 The prevalence of hypertension (blood pressure X16/X95 mmhg) in urban populations increased from 2 4% in mid-195s to 1 15% at the end of 2th century. In rural populations, the Correspondence: Dr R Gupta, Department of Medicine, Monilek Hospital and Research Centre, Jawahar Nagar, Jaipur 324, India. E-mail: rajeevg@satyam.net.in Received 23 November 22; revised 2 April 23; accepted 2 May 23 prevalence increased from 1 2% to 4 8%. The Global Burden of Diseases study has reported that by the year 225, cardiovascular diseases would be the major cause of death all over the world including the developing countries. 4 In India, cardiovascular diseases would result in a loss of 18.4 million disability adjusted life years (DALY s), which is comparable to established market economies (19.4), former socialist economies (26.1), China (16.3), other Asian countries (15.6), Latin America (13.2), and the middle eastern crescent (17.7). High blood pressure (BP) is directly related to about 4% of this cardiovascular disease burden. 5 Increasing hypertension in India and other developing countries has been related to sedentary lifestyle, excess dietary salt, calorie and alcohol intake, increasing generalized and central obesity, and stress of migration and urbanization. 1,2 It has also been proposed that hypertensive individuals are genetically predisposed and that hypertension
536 occurs in only those with a strong genetic contribution. 6,7 Studies on monozygotic and dizygotic twins have reported a strong genetic component in hypertension. 8,9 The role of environmental influences has been reported as being relatively minor by some 6,7 and important by others. 1 14 If hypertension was predominantly genetic, increase in mean BP in populations over time would be associated with unchanged measures of dispersion (variance, standard deviations, coefficient of variation, etc). 11 The proportion of subjects with different subtypes of hypertension would remain constant and the increasing prevalence of hypertension would translate into increases in less severe forms of hypertension, that is, high normal BP (13 139 systolic mmhg and/or diastolic 85 89 mmhg) or stage I hypertension (14 159/9 99 mmhg). 15 Epidemiological studies provide a useful tool to assess the changing patterns of BP distribution in a population. 16,17 Studies from developed countries have reported that increase in mean BP resulted in a higher prevalence of hypertension. 18 An increasing positive skew in BP distribution curves was associated with escalating hypertension prevalence and vice versa. Studies did not report the influence of increasing variance of BP distribution. We performed serial hypertension epidemiological studies in urban subjects in India (first study 1995, 19 second study 22 2 ) to determine change in hypertension prevalence and the influence of age-specific BP statistics on the prevalence of hypertension and subtypes. Methods BP trends in urban Indian subjects The institution ethics committee approved the studies. A proforma was prepared that incorporated information regarding demographic, anthropometric and clinical variables. Details of major cardiovascular risk factors such as smoking, alcohol intake, amount of physical activity, diabetes and hypertension were inquired. The physical examination emphasized measurement of height, weight, waist hip ratio and BP. Height was measured in centimetres and weight in kilograms using a calibrated spring-balance. Supine waist girth was measured at the level of umbilicus with the person breathing silently and standing hip girth was measured at the inter-trochanteric level. BP was measured using a standard mercury manometer. At least two readings at 5 min intervals as per World Health Organization guidelines were recorded. If a high BP (X14/ 9 mmhg) was noted, a third reading was taken after 3 min. 21 The lowest of the three readings was taken as BP as reported earlier. 17 Persons with known hypertension on treatment were considered to have stage II hypertension and the BP values were accordingly modified. The study was designed to investigate people at random and to cover large and varied areas of the city of Jaipur with a view to include persons from all walks of urban life. The city is divided into 7 zones according to a publication of the Municipal Council. Randomly chosen zones from different regions of the city were identified so as to cover different socioeconomic groups. Details of the population in these zones were available from the voters lists. The men : women ratio in the adult population (42 years) is 1 : 865 (Census of India, 1991). In the first study in 1992 1994 (Jaipur Heart Watch-1, JHW-1), 19 we randomly selected 5 subjects from each locality (men 268, women 232) and a total of 3 subjects (men 168, women 1392) were invited for participation. In the second study in 1999 21 (Jaipur Heart Watch-2, JHW-2), 2 we invited 3 subjects (24 men, 16 women) from each locality. The total study sample was 18 with a population-proportionate gender ratio and 96 men and 84 women were invited for participation. No effort was made to enroll the same individuals for both the studies as was done in a recent Chinese study. 22 The studies were preceded by meetings with local leaders who cooperated in identifying and ensuring the participation of selected subjects. Diagnostic criteria Similar criteria were used in the first and the second studies. 19,2 All types of tobacco users, present and past smokers, have been included in the smoker category. A person who engaged in 43 min of moderate grade physical activity at least three times/ week was classified as physically active. Hypertension was diagnosed when either a subject was a known hypertensive or systolic BP was X14 mmhg and/or diastolic BP X9 mmhg. Hypertension was subclassified according to the JNC-VI 15 guidelines into stage I (systolic 14 159 and/or diastolic 9 99 mmhg), stage II (known hypertension or systolic 16 179 and/or diastolic 1 19 mmhg) and stage III (known or systolic X18 and/or diastolic X11 mmhg). Prevalence of high normal BP (systolic 12 129 and/or diastolic 85 89 mmhg) was also determined. Body mass index (BMI) (weight in kg)/(height in metres) 2 was calculated and obesity defined as BMI X27 kg/m 2. Statistical analysis The data were pooled and computerized. SPSS V4..1 (SPSS Inc., Chicago, USA) and GB-Stat V7. (Dynamic Microsystems, Silver Spring, USA) programs were used for data analysis. Various numbers are reported as mean 7 1 s.d. Standard normal curves of age-specific systolic and diastolic BP levels were plotted. Skewness of the distribution was determined using absolute systolic BP values by the SPSS package. The prevalence rates are given in percent. There was difference in age distribution in the two studies and risk factor comparison in the
BP trends in urban Indian subjects first and the second study was performed after age adjustment using the direct method. Continuous variables have been compared using t-test and categorical variables by w 2 test. A P-value ofo.5 has been considered significant. 5 Men 15 1 2 Women 1 537 Results The overall response rate in the first study was 73.7% (2212/3): 1415/168 (88.%) in men and 797/1392 (57.3%) in women. In the second study, the overall response rate was 62.4% (1123/18), in men it was 55/96 (57.3%) and in women 573/84 (68.2%). Analysable BP values were available for all these individuals. The age-specific BP levels in the first and second study are reported in Table 1. The mean values of systolic and diastolic BP are not significantly different in different age groups in the first and the second studies. There is an increased variance in the second study as denoted by the significant increase in standard deviations and coefficients of variation in systolic as well as diastolic BP levels especially in age groups 5 59 and 6 69 years in men, and 4 49, 5 59 and 6 69 years in women (Po.5). The standard normal curves for systolic BP in JHW-1 and JHW-2 are shown in Figure 1. There is a positive skew (increased right tail of the standard normal curve) in BP distribution in both JHW-1 and JHW-2. Markers of distribution of systolic BP in JHW-1 were compared with JHW-2. As compared to JHW-1 in JHW-2, the skewness (men 1.22 7.7 vs 2.63 7.1; women.84 7.9 vs 1.15 7.1 units) as well as kurtosis (men 2.56 7.13 vs 33.6 7.21; women.43 7.17 vs 2.6 7.21 units) are significantly greater (Po.5). Prevalence of hypertension in the first and second study is shown in Table 2. Hypertension was present 25 5 Figure 1 Frequency distribution of systolic BP in JHW-1 (solid lines) and JHW-2 (dashed lines) in men and women. The BP distributions show a positive skew. in 417 men (29.5%) and 267 women (33.5%) in the first study (JHW-1). Crude prevalence of hypertension in the second study (JHW-2) is 2 in men (36.4%) and 215 in women (37.5%), but the ageadjusted prevalence rates are not significantly different in the two studies in both men (29.5 vs 3.%, P ¼.87) and women (33.5 vs 3.3%, P ¼.23). The prevalence of hypertension increases with age in both men and women (Mantel Haenzel w 2 for trend Po.5), but there is no significant difference in age-specific prevalence rates in JHW-1 and JHW-2. The overall age-adjusted prevalence of high normal BP 15 in the first and second studies (men 13.9 vs 15.5%, women 11.9 vs 1.9%) is not significantly different. The prevalence of stage I hypertension 15 is significantly greater in JHW-1 as compared to JHW-2 (men 24.9 vs 16.8%, women 27.5 vs 15.4%, Po.1), while the prevalence of stage II hypertension is significantly lower in JHW-1 vs JHW-2 (2.8 vs 11.7%, women 3.1 vs 18.8%, Po.1). There is no significant difference in the 1 5 Table 1 Age-specific BP levels in JHW-1 and JHW-2 Age group (years) JHW-1 JHW-2 Systolic BP Diastolic BP JHW-1 JHW-2 JHW-1 JHW-2 Men 2 29 526 99 119 7 12 (1.1) 117 7 12 (1.2) 77 7 7 (9.1) 77 7 9 (11.7) 3 39 374 153 123 7 13 (1.6) 118 7 15 (12.7) 8 7 8 (1.6) 77 7 12 (15.6) 4 49 183 117 129 7 17 (13.2) 122 7 18 (14.8) 83 7 1 (12.1) 81 7 13 (16.) 5 59 211 1 135 7 19 (14.1) 128 7 23 (18.) 86 7 1 (11.6) 83 7 14 (16.9) 6 69 72 56 134 7 2 (14.9) 131 7 26 (2.) 84 7 1 (11.9) 78 7 14 (17.9) 7+ 4 25 139 7 22 (15.8) 136 7 2 (14.7) 84 7 1 (11.9) 77 7 1 (13.) Women 2 29 136 9 115 7 12 (1.4) 16 7 12 (11.3) 75 7 8 (1.7) 7 7 1 (14.3) 3 39 157 151 117 7 15 (12.8) 115 7 17 (14.8) 78 7 1 (12.8) 75 7 11 (14.7) 4 49 211 132 124 7 15 (12.1) 122 7 2 (16.4) 79 7 8 (1.1) 79 7 13 (16.5) 5 59 151 113 137 7 21 (15.3) 131 7 22 (16.8) 86 7 12 (13.9) 82 7 13 (15.9) 6 69 86 139 7 23 (16.5) 138 7 31 (22.5) 87 7 12 (13.8) 78 7 14 (17.9) 7+ 56 132 7 27 (2.4) 142 7 27 (19.) 83 7 11 (13.3) 81 7 16 (19.8) Numbers in parentheses are coefficients of variation.
BP trends in urban Indian subjects 538 Table 2 Hypertension prevalence in the first study (JHW-1, 1995) and the second study (JHW-2, 22) Age groups (years) Men Women JHW-1 (N=1412) JHW-2 (N=55) JHW-1 (N=797) JHW-2 (N=573) 2 29 65/526 (12.4) 13/99 (13.1) 8/136 (5.9) 6/9 (6.7) 3 39 87/374 (23.3) 42/153 (27.4) 24/157 (15.3) 36/151 (23.8) 4 49 71/183 (38.8) 46/117 (39.3) 66/211 (31.3) 54/132 (4.9) 5 59 129/211 (61.1) 54/1 (54.) 94/151 (62.2) 62/113 (54.9) 6+ 65/121 (53.7) 45/78 (55.6) 75/142 (52.8) 57/87 (65.5) Total 417/1415 (29.5) 2/55 (36.4) 267/797 (33.5) 215/573 (37.5) Age adjusted F 3.% F 3.3% Numbers in parentheses are percent. prevalence of stage III hypertension. It is also observed that prevalence of higher grades of hypertension (stages II and III) is significantly greater in JHW-2 when compared to JHW-1 (men 13.5 vs 4.7%, women 16.7 vs 6.%, Po.1). Discussion The present study shows that increased systolic and diastolic BP dispersion without change in the mean BP over a 7-year period in this urban Indian population is associated with unchanged total hypertension prevalence, decline in stage I hypertension and increase in more severe grades of hypertension. In various cohorts of the Seven Countries Study, 18 trends in prevalence of hypertension and BP were determined. In the Yugoslavian cohort 23 as compared to a baseline systolic BP of 131.4 7 18.5 mmhg in the years 1962 1964, after 5 years the BP was 129.7 7 18.3 mmhg and after 1 years 144.1 7 22.4 mmhg. Similar trends were seen in Zrenjanin (baseline 133.5 7 18.7 mmhg, 5 years 144.2 7 23.7 mmhg and 1 years 149. 7 25.5 mmhg) and Beograd (baseline 133.8 7 18. mmhg, 5 years 135.6 7 2.4 mmhg and 1 years 144. 7 21.4 mmhg) rural areas. This was associated with increasing hypertension prevalence. In Crete 24 among men aged 55 59 years, a decline in mean systolic BP from 138 mmhg (1962) to 13. mmhg (1982) was associated with a decline in hypertension prevalence. In the Dutch cohort 25 in the period 1974 198, the average systolic BP increased by 2 mmhg, diastolic BP increased by 4 mmhg and the prevalence of hypertension increased from 12.7% in 1974 to 17.8% in 198. In the Minnesota cohort, Jacobs et al 26 reported that decrease in systolic BP of.56 7.7 mmhg per year resulted in a significant decline in hypertension prevalence. The WHO-MONICA study reported that in various international cohorts, mean levels of systolic BP either declined or did not change significantly. 27 Average annual change of systolic BP ranged from 1.73 to.12 mmhg with a standard error of.17.42. Prevalence of hypertension varied with changing mean BP. The Framingham study reported that a decline in mean systolic and diastolic BP over a 4-year period was associated with declining hypertension prevalence. 28 In men, mean systolic BP declined from 137.4 mmhg in the 195s to 137.3 mmhg in the 196s, 134.7 mmhg in the 197s and 133.2 mmhg in the 198s (change of 1.6 per decade). In women, it declined from 145.3 to 139.9, 132.6, and 13.4 mmhg, respectively ( 4.7 per decade). Similar declines were seen in diastolic BP (men 1.5 mmhg, women 2.5 mmhg per decade). There was decrease in stage 2 (men, 29%, women, 42%), stage 3 (men, 42%, women, 54%) as well as stage 4 (men, 63%, women, 68%) hypertension. The BP variance was not reported and we cannot therefore compare our results with these studies. Ahlawat et al 29 reported trends in hypertension in an urban north Indian population over a 3-year period. Prevalence of hypertension in 1968 was 19.9% in men and 24.8% in women and increased to 43.7% in men and 45.8% in women in 1997. 29 Changes in mean BP levels were not reported. In Delhi, mean systolic BP increased in men aged 4 49 years from 123.4 7 11 mmhg in 1959 to 128.8 7 17 mmhg in 1995. 2 This was associated with increase in the prevalence of hypertension from 6.3 to 26.4%. Yu et al 22 in China reported unchanged mean BP levels over 7 years in an urban population and no change in hypertension prevalence. The mean systolic BP in men was 128.3 7 2.4 mmhg in the first and 127.4 7 16.8 mmhg in the second study, and in women it was 125.7 7 23.9 and 123.5 7 2.1 mmhg, respectively. Hypertension prevalence in men was 28 and 29% and in women 25 and 24% in the two studies. The present study also shows unchanged mean BP in this population in the years 1995 and 22 with no change in hypertension prevalence. None of these studies reported on hypertension subtypes, so it is difficult to compare our results. Estimates of change in the level of a risk factor are affected by
several factors: the true average change in the population, variation between subjects, measurement errors and effects due to sample selection. Although we have tried to minimize these factors using proper sample selection and meticulous measurement methods, their influence cannot be excluded. Platt 6 initially developed a mathematical model for hypertension and showed that population BP levels have a bimodal distribution, the initial large peak representing normal subjects and the second smaller peak representing subjects with genetic type of hypertension. This hypothesis, however, failed to account for a very large prevalence of hypertension in the general population. Pickering 12 reanalysed the population s BP distribution and suggested that positively skewed standard normal curve showed importance of environmental influences in hypertension. Harrap 13 reported a considerable overlap in the bimodal curve and argued that there was a strong gene environment interaction in the pathogenesis of essential hypertension. Twin studies have demonstrated that there is a significant contribution of genetic factors on hypertension incidence. 8,9 An Indian study also concluded that genetic factors are important in hypertension. 3 The present study involves subjects who are genetically similar. Hence, the frequency distribution of BP essentially remains the same (Figure 1). Increased variance has resulted in a decline in the prevalence of stage I hypertension and an increase in stage II hypertension. The study of genetic and environmental factors in complex diseases such as hypertension is difficult. It has been suggested that in the present postgenome era it is important to understand the use of genetic associations to test causal pathways rather than model joint effects of genotype and environment. 31 Trends in atherosclerosis risk factors in the present study subjects have been reported previously. 2 In both JHW-1 and JHW-2, high prevalence of sedentary lifestyle (men 7.9 vs 61.5%, women 72.4 vs 63.2%, P ¼ NS) and truncal obesity (men 51.2 vs 5.9%, women 67.9 vs 67.8%, P ¼ NS) was observed. Obesity (BMI X27 kg/m 2 ) increased from 11.2 to 22.3% in men and 13.2 to 29.7% in women (Po.1). Obesity is strongly related to hypertension in India and other countries. 2,18,29 It appears that increase in obesity is responsible for the large increase in stage II hypertension in this population. Subjects genetically predisposed to hypertension have evolved from stage I to stage II due to increase in obesity, which is a major hypertension risk factor. Ezzati et al 32 have reported results of global disease burden in the year 2 (GBD-2). In the GBD-2 study, hypertension has been projected as the most important risk factor accounting for 7.14 million deaths of a total of 55.8 million (12.8%) worldwide. This is more than deaths caused by underweight (3.75 million), high cholesterol (4.42 million), tobacco (4.91 million), unsafe sex (2.89 BP trends in urban Indian subjects million) and other risk factors. In the present study, increase in multiple metabolic risk factors along with the increase in more severe grades of hypertension heralds a major cardiovascular disease epidemic in India as predicted by GBD-2. In conclusion, the increasing variance in BP distribution in this urban Indian population has resulted in a significant increase in severe forms of hypertension. 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