The effects of awareness, treatment and control of hypertension on cardiovascular and all-cause mortality in a communitybased

Transcription

1 (2009) 23, & 2009 Macmillan Publishers Limited All rights reserved /09 $ ORIGINAL ARTICLE The effects of awareness, treatment and control of hypertension on cardiovascular and all-cause mortality in a communitybased population NC Barengo 1,2, M Kastarinen 3, R Antikainen 4,5, A Nissinen 6 and J Tuomilehto 1,7 1 Department of Public Health, University of Helsinki, Helsinki, Finland; 2 Unit of Epidemiology and Clinical Research, University Hospital La Paz, Madrid, Spain; 3 Department of Internal Medicine, Kuopio University Hospital, Kuopio, Finland; 4 Oulu City Hospital, Oulu, Finland; 5 Division of Medicine, Imperial College, London, UK; 6 Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland and 7 South Ostrobothnia Central Hospital, Seinäjoki, Finland The objective of this prospective follow-up study (median follow-up time 20 years) was to investigate whether there are differences in cardiovascular disease (CVD) and all-cause mortality among hypertensive men and women by awareness, treatment and blood pressure (BP) control status. The study was carried out among men and women aged years living in Eastern and south-western Finland within the framework of the North Karelia Project and the Finrisk studies. Risk factors of CVD and life-style habits were assessed by a self-administered questionnaire, BP and laboratory measurements. The participants were classified into five groups according to their BP status: (i) normotensive, (ii) patients treated with antihypertensive drugs and controlled for HT, (iii) patients treated with antihypertensive drugs but uncontrolled for HT, (iv) hypertensive people aware of their HT but untreated, (v) hypertensive people unaware of their hypertension (HT). In men, all-cause and CVD mortality was significantly higher in all HT subgroups compared with the normotensive group. The risk increase for CVD mortality was % and 27 79% for all-cause mortality, respectively. Treated and controlled hypertensive women at baseline did not have any increase in CVD (hazard ratio (HR) 1.14; 95% CI ) or all-cause mortality (HR 1.09; 95% CI ) compared with normotensive women. In men, however, the corresponding HR were 1.58 (95% CI ) for CVD and 2.25 (95% CI ) for all-cause mortality. Treated hypertensive women seem to benefit from achieving normal BP. (2009) 23, ; doi: /jhh ; published online 16 April 2009 Keywords: mortality; cardiovascular disease; antihypertensive drug treatment Introduction There is a firm evidence from epidemiological studies, that elevated blood pressure (BP) is an independent and strong predictor for cardiovascular disease (CVD). 1,2 Worldwide, 7.1 million deaths (approximately 12.8% of the global total) and 64.3 million DALYs (4.4% of the global total) were estimated to be due to non-optimal blood pressure. 3 The benefit of antihypertensive treatments in reducing the risk for cardiovascular events in persons with high BP has been well established in multitude of randomised trials but they usually had a Correspondence: Dr NC Barengo, Department of Public Health, University of Helsinki, University of Helsinki, Helsinki, Finland. noel.barengo@uku.fi Received 24 November 2008; revised 4 March 2009; accepted 26 March 2009; published online 16 April 2009 relatively short follow-up. 4 5 In light of this evidence, it can be nevertheless predicted that successful treatment of hypertension (HT) may reduce CVD and all-cause mortality at the population level. Studies comparing CVD and all-cause mortality between treated hypertensive patients with normotensive individuals showed that treated hypertensive patients with normalised BP are still at higher risk for CVDs than normotensive persons. 6 9 Controversial results have been published regarding health outcomes in normotensive people with health outcomes in treated and untreated hypertensive patients Furthermore studies including women are rare. 10,12,15 The aim of this study was to investigate whether there are differences in CVD and all-cause mortality among hypertensive men and women by awareness, treatment and the BP control status at baseline.

2 Materials and methods Study population Since 1972, six independent cross-sectional surveys were carried out at 5-year intervals within the framework of the North Karelia Project and the FINMONICA/Finrisk studies. 16 An independent random sample was drawn from the national population register for each survey. In the first two surveys (1972, 1977) separate independent random samples of 6.6% of the middle-aged population were drawn in both areas. In 1982, 1987, 1992 and 1997, the samples were stratified by sex and 10-year age categories according to the WHO MONICA protocol. 17 The surveys methods followed the WHO MONICA protocol and were comparable with the methods used in 1972 and The FINMONICA study is the Finnish part of the multinational MONICA project initiated by WHO in The first two surveys were conducted in two regions: the provinces of North Karelia and Kuopio which are both located in eastern Finland. The survey expanded to the region of Turku Loimaa in south-western Finland in 1982 and to other regions in 1992 (Helsinki and Oulu). Participants who took part in more than one survey were included only in their first survey cohort. The total sample included people. The participation rates varied between 71 and 94% in men and between 78 and 95% in women. Informed written content was obtained starting from the participants of the 1977 survey. At the time of the earlier survey it was not customary in Finland to ask for a written consent, but the participants were informed about the purpose of the study both in written and oral form. Each risk factor survey has been approved by the Institutional Review Board (IRB) before being carried out. People who were earlier diagnosed with coronary heart disease (angina pectoris, infarction, n ¼ 2113), stroke (n ¼ 380), heart failure (n ¼ 1624) or cancer (n ¼ 132) at baseline, and those who were physically inactive because of severe disease or disability at baseline (n ¼ 1879) were excluded from the study. After a further exclusion of individuals with incomplete data on physical activity (n ¼ 2271), height or weight (n ¼ 793), serum cholesterol (n ¼ 201), smoking (n ¼ 852) or blood pressure (n ¼ 27) the final sample comprised men and women. Assessment of risk factors for CVD Self-reported smoking habits were classified according to three categories: never smokers, ex-smokers (those, who had smoked regularly but had stopped smoking at least 6 months before the survey) and current smokers. Education was categorised in years and the subjects were divided in following categories: (i) low, 0 6 years of schooling; (ii) middle, 7 9 years of schooling; (iii) high, 49 years of schooling. Height, weight and blood pressure were measured by nurses specially trained for the survey procedures. Height was measured to the nearest 0.5 cm. Weight was measure in light clothing. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Blood pressure was measured twice from the right arm of the participant, using a standard mercury sphygmomanometer. The fifth phase of the Korotkoff s sound was recorded as the diastolic BP. In 1972 and 1977, BP was measured once and a shorter cuff bladder (23 cm) was used than in later surveys (42 cm long and 13 cm wide (1982 and 1987), 14 cm wide and 40 cm long in (1992 and 1997), respectively). Since 1982, BP was measured twice and the mean of these two BP measurements was used in the analyses. A person was considered to have hypertension when the average BP was at least 160 mm Hg systolic or 95 mm Hg diastolic, or if he or she reported having taken antihypertensive drugs during the preceding 7 days. Since 1982, BP was measured twice and the mean of these two BP measurements was used in the analyses. A person was considered to have hypertension when the average BP was at least 160 mm Hg systolic or 95 mm Hg diastolic, or if he or she reported having taken antihypertensive drugs during the preceding 7 days. The reason for choosing these BP levels rather than currently recommended 140/90 mm Hg for the definition of hypertension is that during most of the follow-up these were the official treatment thresholds of the national guidelines in Finland. 18 Information on awareness of hypertension the use of antihypertensive drugs was obtained with a selfadministered questionnaire. Awareness of hypertension was defined as a participants having reported an earlier diagnosis of hypertension or current use of antihypertensive drug treatment. People on antihypertensive drug treatment, whose measured BP level was o160/95 mm Hg, were considered to be adequately treated (controlled) in this analysis. The study population was classified into five groups according to their BP status: (i) normotensive participants (measured BP level o160/95 mm Hg and without any hypertensive drug treatment); (ii) hypertensive patients treated with antihypertensive drugs and controlled for HT; (iii) hypertensive patients treated with antihypertensive drugs and uncontrolled for HT (iv) hypertensive people aware of their hypertensive status but untreated; (v) unaware and untreated hypertensive patients. Total cholesterol was determined by using Lieberman Burchard method in 1972 and 1977, and an enzymatic method (CHOD-PAP, Boehringer Mannheim, Mannheim, Germany) since As the enzymatic method gave 2.4% lower values than the Lieberman Burchard method, 1972 and 1977 values are corrected by this percentage. All samples were analysed in the same central laboratory. Participants who reported having diabetes on the questionnaire, or who had had a hospital discharge 809

3 810 diagnosis of diabetes, or the approval for free-ofcharge medication for diabetes before the baseline survey or during the follow-up were classified as having diabetes. Data on diabetes medication were ascertained from the national Social Insurance Institution s register on special reimbursement for anti-diabetic drugs from Anti-diabetic drugs prescribed by a physician are free of charge in Finland and are subject to approval of a physician of the Institution who reviews each case history. Leisure-time physical activity, occupational physical activity and commuting activity were determined by a self-administered questionnaire. The time frame of the activity questionnaire was a typical week. Leisure-time physical activity was classified as follows: (i) high: participation in recreational sports (for example, running, jogging, skiing, gymnastics, swimming, ball-games or heavy gardening) or in intense training or sports competitions for at least 3 h a week; (ii) moderate: walking, cycling or practising some other form of light exercise (fishing, gardening and hunting) at least 4 h per week; (iii) low: reading, watching TV or working in the household without much physical activity. Occupational physical activity was classified as follows: (i) high: lots of walking and lifting at work, taking the stairs or walking uphill (for example industrial work, farm work, forestry); (ii) moderate: walking quite a lot at work without lifting or carrying heavy objects; (iii) low: mostly sedentary work without much walking (for example, working in an office). Commuting activity was classified as follows: (i) high: 430 min physical exercise (walking, cycling) every day while getting to work and back home; (ii) moderate: exercising between 15 and 30 min daily on the way to work and back home; (iii) low: exercising o15 min daily on the way to work and back home. Women with moderate and high leisure-time physical activity, occupational physical activity and commuting activity were combined because there were only a few outcome events in each category. Outcome definition The original survey data were complemented by linkage to the nationwide death register of Statistics Finland according the unique national personal identification number that every Finn has. These records covered the period from January 1970 to December The Eighth, Ninth and Tenth Revisions of the International Classification of Diseases were used for coding the causes of death. The codes used for CVD were (I00 I99). The end point of the follow-up was the date of death. The follow-up ended by the end of December Altogether, we identified 3616 cases of death in men (1680 due to CVD) and 2012 in women (812 due to CVD), respectively during a median followup time of 20 years. Statistical analyses Statistical analyses were carried out with SPSS for Windows The Cox proportional hazards model was used to estimate the association between hypertension subgroups and the risk for total and CVD mortality. Analyses were adjusted first for age, study area and study year (A) for then for age, study region, study year, education, smoking status, systolic blood pressure (SBP), cholesterol level, BMI (B) and finally also for physical activity (C). The data of all six surveys were pooled together, because no first-level interaction was found between blood pressure treatment groups and these variables regarding CVD or total mortality. Blood pressure group variables were entered into the model as categorical variables, and the statistical significance of different categories of physical activity was tested in the same models, with the normotensive category as reference group. The proportional hazards assumption in the Cox model was assessed with graphical methods. Estimated hazard ratios and their 95% confidence intervals (CI) are presented. Results The baseline characteristics of the study population are presented in Table 1 (men) and Table 2 (women). Normotensive men and women seemed to have lower initial BMI than the people classified to one of the three hypertensive groups. Smoking prevalence was lowest in the treated hypertensive group. In contrast, the prevalence of diabetes, was highest in treated hypertensive people, and those with treated and controlled hypertension had a lower serum cholesterol level than participants treated, but uncontrolled for hypertension. During a median follow-up of 20 years, 3615 men died, 56% due to CVD, and among the deceased women 40% (total deaths 2012) were due to CVD (Table 3 and 4). All-cause mortality was higher in all four hypertensive subgroups among both men and women compared with the normotensive groups (Table 3). The increase in all-cause mortality was between 58% and 79% (95% CI %) among men who were treated with antihypertensive drugs and 46% (95% CI 31 63%) among those who were aware of being hypertensive but untreated at baseline when adjusted for age, BMI, smoking, serum cholesterol, education, diabetes SBP and different forms of physical activity. Treated hypertensive women with controlled hypertension did not experience a significant increase in mortality from all-causes compared with normotensive ones. Treated hypertensive women with uncontrolled HT (HR 1.64), those aware but untreated hypertension (HR 1.44) and those unaware and with untreated

4 Table 1 Baseline characteristics in normotensive and different categories of hypertensive men 811 Normotensive Hypertensive, treated, controlled Hypertensive, treated, uncontrolled Hypertensive, aware but untreated Hypertensive, unaware and untreated (n) Age (years) 40.1 (10.4) a 52.4 (9.2) a 51.9 (9.3) a 45.8 (10.2) a 44.8 (10.5) a Education (years) 10.1 (3.9) a 9.2 (3.9) a 8.6 (3.7) a 9.2 (3.7) a 8.4 (3.4) a Body mass index (kg m 2 ) (3.18) a 28.8 (4.34) a 28.8 (4.13) a (3.85) a (3.61) a Systolic blood pressure 134 (12) a 139 (12) a 162 (18) a 164 (18) a 158 (16) a Diastolic blood pressure 82 (9) a 87 (6) a 102 (10) a 101 (10) a 99 (9) a Serum cholesterol 6.03 (1.24) a 6.05 (1.10) a 6.44 (1.26) a 6.48 (1.26) a 6.66 (1.28) a Smoking (%) Never Ever Current Diabetes (%) No Yes Leisure-time physical activity (%) Low Moderate High Occupational physical activity (%) Low Moderate High Commuting activity (%) o15 min per day min per day min per day a Mean (standard deviation). hypertension (HR 1.39) all had significantly increased mortality risk. The increase in CVD mortality remained significant after adjustments (HR 2.25; 95% CI ) for hypertensive treated and controlled men (Table 4). However, there was no statistically significant increase in CVD mortality in hypertensive women whose BP was controlled compared with normotensive women (HR 1.09 (95% CI )). Discussion This prospective population-based observational study with a median follow-up time of 20 years shows that both men and women with uncontrolled hypertension at baseline have a higher risk of CVD and all-cause mortality than normotensive people. Hypertensive women who have adequately controlled blood pressur seem to have no increase in the risk of CVD and all-cause mortality. Our results in men are in line with the Primary Preventive Study in Gothenburg reporting that despite of rather good blood pressure control, there was a significantly increased mortality rate in treated hypertensive patients compared with normotensive individuals. 6 8 Almgren et al. 6 showed in a years follow-up of a cohort of men with antihypertensive therapy that coronary heart disease mortality was almost doubled in treated hypertensive men compared with normotensive men. Total mortality was increased by about one third in treated hypertensive patients. In contrast to our study, the Copenhagen City Heart Study did not find a significant difference in CVD mortality between patients receiving antihypertensive medication and normotensive people. 9 However, their hazard ratio for all-cause mortality in patients with antihypertensive treatment was statistically significantly increased (HR 1.7 (95% CI )) as shown in our study, too. The most likely explanation for the difference in CVD and all-cause mortality risk between hypertensive and nonhypertensive patients is that hypertensive patients are more exposed to atherosclerotic risk and target-organ damage already before and probably also during therapy if BP remains high. Furthermore, there was a substantial difference in risk factor profile between hypertensive and nonhypertensive people already at baseline. BMI and serum cholesterol levels were significantly lower in the normotensive group than in the hypertensive groups.

5 812 Table 2 Baseline characteristics in normotensive and different categories of hypertensive women Normotensive Hypertensive, treated, controlled Hypertensive, treated, uncontrolled Hypertensive, aware but untreated Hypertensive, unaware and untreated n Age (years) 40.7 (10.5) a 52.7 (8.3) a 52.8 (7.8) a 47.5 (9.4) a 49.9 (9.5) a Education (years) 10.6 (3.8) 8.9 (3.3) a 7.8 (3.3) a 8.7 (3.5) a 7.8 (3.4) a Body mass index (kg m 2 ) (3.98) a (5.00) a (5.21) a (5.05) a (4.44) a Systolic blood pressure 128 (14) a 140 (12) a 170 (19) a 167 (19) a 164 (19) a Diastolic blood pressure 79 (9) a 86 (6) a 100 (10) a 99 (10) a 97 (9) a Serum cholesterol 5.81 (1.23) a 6.24 (1.22) a 6.88 (1.39) a 6.60 (1.31) a 6.83 (1.42) a Smoking (%) Never Ever Current Diabetes (%) No Yes Leisure-time physical activity (%) Low Moderate High Occupational physical activity (%) Low Moderate High Commuting activity (%) o15 min per day min per day min per day a Mean (standard deviation). Table 3 Hazard ratios (HRs) for total mortality in normotensive a subjects and in different categories of hypertensive subjects, with various forms of adjustment b Number of deaths Person-years Adjusted HRs (95% confidence interval) A B C All-cause mortality Men Normotensive Hypertensive, treated, controlled ( ) 1.60 ( ) 1.58 ( ) Hypertensive, treated, uncontrolled ( ) 1.83 ( ) 1.79 ( ) Hypertensive, aware but untreated ( ) 1.47 ( ) 1.46 ( ) Hypertensive, unaware, untreated ( ) 1.28 ( ) 1.27 ( ) Women Normotensive Hypertensive, treated, controlled ( ) 1.17 ( ) 1.14 ( ) Hypertensive, treated, uncontrolled ( ) 1.67 ( ) 1.64 ( ) Hypertensive, aware but untreated ( ) 1.44 ( ) 1.44 ( ) Hypertensive, unaware, untreated ( ) 1.39 ( ) 1.39 ( ) a Measured BP level o160/95 mm Hg and without any hypertensive drug treatment. b A, adjusted for age, study area and study year; B, adjusted for age, study area, study year, body mass index, serum cholesterol, systolic blood pressure, education, diabetes and smoking status; C, adjusted for age, study area, study year, body mass index, serum cholesterol, education, diabetes, smoking status, leisure-time physical activity, occupational physical activity and commuting activity. The findings in studies comparing treated with untreated hypertensive people are controversial. The Reykjavik Study compared controlled people with controlled and uncontrolled hypertension at baseline in a 30-year follow-up regarding CVD mortality. 10 They reported that the level of control of blood pressure among hypertensive-treated individuals at baseline was associated with a lower

6 Table 4 Hazard ratios (HRs) for cardiovascular mortality in normotensive a subjects and in different categories of hypertensive subjects with various forms of adjustment b 813 Number of deaths Person-years Adjusted HRs (95% confidence interval) A B C Cardiovascular mortality Men Normotensive Hypertensive, treated, controlled ( ) 2.27 ( ) 2.25 ( ) Hypertensive, treated, uncontrolled ( ) 2.44 ( ) 2.41 ( ) Hypertensive, aware but untreated ( ) 1.93 ( ) 1.92 ( ) Hypertensive, unaware, untreated ( ) 1.50 ( ) 1.49 ( ) Women Normotensive Hypertensive, treated, controlled ( ) 1.12 ( ) 1.09 ( ) Hypertensive, treated, uncontrolled ( ) 2.44 ( ) 2.40 ( ) Hypertensive, aware but untreated ( ) 2.05 ( ) 2.03 ( ) Hypertensive, unaware, untreated ( ) 1.67 ( ) 1.67 ( ) a Measured BP level o160/95 mm Hg and without any hypertensive drug treatment. b A, adjusted for age, study area and study year; B, adjusted for age, study area, study year, body mass index, serum cholesterol, systolic blood pressure, education, diabetes and smoking status; C, adjusted for age, study area, study year, body mass index, serum cholesterol, education, diabetes, smoking status, leisure-time physical activity, occupational physical activity and commuting activity. risk of CVD mortality in men and in women. It is interesting that, during the first ten years of followup, treated men had a higher risk for CVD mortality than those who were untreated, which was most likely because of a worse baseline risk profile. 10 However, no differences regarding all-cause mortality were found. 19 A cohort study from the Department of Health Hypertension Care Computing Project reported that men and women with controlled hypertension were at lower risk of ischemic heart disease and stroke mortality compared with men and women with uncontrolled hypertension. 12 Furthermore, a study on 4714 treated hypertensive men with a mean follow-up of 14 years showed that after adjusting for age and associated risk factors, men with uncontrolled blood pressure were at higher risk for CVD mortality than hypertensive men who had their blood pressure controlled. 14 Few studies did not find any effect of hypertension treatment on CVD mortality. 11,13,15 However, their follow-up times were rather short, 7 years 11 and 5 years, 13 respectively, and it may be argued that exposure time was not sufficient to show any beneficial effect of antihypertensive therapy. It is also possible that changes in hypertension care have influenced outcomes obtained during the long-term follow-up. Compared with the treated but uncontrolled patients the patients with treated, controlled hypertension had lower estimates for CVD and all-cause mortality. People with treated, controlled hypertension had much lower blood pressure at which may reflect additionally to the possible effect of treatment also the fact that some of these people have had lower BP even without treatment. Thus, the category controlled, treated hypertension tend to select patients with lower initial CVD risk. Especially in men, adjusted HRs for hypertensive, unaware and untreated participants were lower than in the hypertensive, treated and controlled groups. Most likely patients with treated hypertension have had more severe hypertension. As treated men were older their hypertension and thus the exposure may have persisted longer than in the unaware hypertensive groups. Hypertension care has improved significantly in Finland during 1982 to Nevertheless, the difference between the actual situation at the population level and the treatment goals presented by the hypertension guidelines remains far from optimal. 20 Even though the lipid profile of both the hypertensive and normotensive population has significantly improved in both the hypertensive and normotensive population in Finland from , unfavourable trends, however, have been observed in mean BMI and alcohol intake in the entire population in Finland Thus, it has been suggested that the health behaviours of hypertensive people should be carefully monitored and modified in a more systematic and efficient way than at present. 21 Even though antihypertensive drug treatment has probably contributed significantly to the decrease of BP in treated hypertensive patients, drug treatment can explain only part of the decline of the BP level in the entire population A community approach with mainly nonpharmacological treatment produces reductions in blood pressure levels and is cost effective in reducing CVD morbidity and mortality. 28,29 This is consistent with the recent guidelines that indicate that the prognosis of hypertensive individuals largely depends on risk factors other than BP alone, including comorbidity and the targetorgan damage. 30,31 At the population level, severe

7 814 hypertension leads to considerable losses in terms of years of life lost, years of work lost and costs. 32 As we pointed out, we chose as cut-off levels for the definition of high blood pressure 160/95 mm Hg rather than the currently recommended 140/ 90 mm Hg because during most of the follow-up time these were the official treatment thresholds and targets according to the national guidelines in Finland. 18 We carried out some analysis using the currently recommended cut-off levels as well. However, the number of people in the hypertensive treated and controlled group become too small in both men and women for meaningful statistical analysis. It has been shown that besides education, also other social factors such as marital status and occupation influence prognosis in hypertensive patients. 33 Further studies may address specifically the influence of these factors in treatment of hypertension. Our study is population based, comprising a large number of men and women from a homogeneous population. The median follow-up, 20 years, was long enough that the largest number of outcome events was ascertained without loss of follow-up. The participation rates were high which makes it possible to apply the results directly to the general population. Furthermore, this is to our knowledge the first study to analyse separately the associations between different subgroups of hypertension among men and women regarding all-cause and CVD mortality. The optimal design for studies like this would be to have follow-up measurements of a large population cohort repeatedly over time. However, this would be very costly and no such cohort exist up-todate investigating effects of hypertension treatment over time. Cross-sectional epidemiological studies are therefore much more common. They provide information about effects that may have a long history (sometimes even life-long), and possible changes after the baseline measurements in crosssectional studies may sometimes have only limited effects on the prognosis of the participants. Specifically, regarding hypertension, the open-label follow-up with active antihypertensive drug therapy after several years of the original placebo-controlled treatment phase of the Syst-eur trial showed that the effects of the initial placebo-controlled treatment were carried over the subsequent 5-year active treatment period. 34 The design used in this study is very commonly used in these kind of studies acknowledging its possible limitations, as we have done. Naturally, our study had some limitations. The baseline assessment of our cohort is limited to a single examination, when subjects entered the study as it is usual for large prospective studies. It cannot control for changes in compliance or a shift of subjects between categories during the study period. We are aware that this may cause misclassification that underestimates the true effect of hypertension control. We cannot completely exclude either effects of residual confounding attributable to the measurement error in the assessment of confounding factors or some unmeasured dietary factors. In addition, we do not have specific information on hypertension treatment in the past or during the follow-up as the effect of different therapeutic options on prognosis of cardiovascular and all-cause mortality may vary. Furthermore, it has to be kept in mind that the results may be affected by white-coat hypertension which is more prevalent in women than men and masked hypertension which is much more common in men than women. 35 What is known about this topic K Elevated blood pressure (BP) is an independent and strong predictor for cardiovascular disease (CVD). K Benefit of antihypertensive treatments in reducing the risk for cardiovascular events in persons with high-bp well established in multitude of randomised trials. K Controversial results regarding health outcomes in normotensive people with health outcomes in treated and untreated hypertensive patients. What this study adds K The risk of CVD and all-cause mortality increased in all groups of hypertensive men in a representative population. K However, hypertension control at baseline in a populationbased cohort seems to be predictive of CVD and all-cause mortality in women alone. K Adequately-treated hypertensive women seem to benefit from achieving normal blood pressure (BP). Acknowledgements This paper was supported by a grant of the Finnish Foundation of Cardiovascular Research, the Academy of Finland (Grant no and the EVO funds from the city of Oulu, Finland. References 1 Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA et al. Blood pressure, stroke and coronary heart disease. Part 2: short term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: Boudik F, Reissigova J, Hrach K, Tomeckova M, Bultas J, Anger Z et al. Primary prevention of coronary artery disease among middle aged men in Prague: twenty-year follow-up results. Atherosclerosis 2006; 184: Lawes CM, Vander Hoorn S, Law MR, Elliott P, MacMahon S, Rodgers A. Blood pressure and the global burden of disease Part II: estimates of attributable burden. J Hypertens 2006; 24: Gueyffier F, Boutitie F, Boissel JP, Pocock S, Coope J, Cutler J et al. Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men.

8 A meta-analysis of individual patient data from randomized, controlled trials. The INDANA Investigators. Ann Intern Med 1997; 126: Psaty BM, Smith NL, Siscovick DS, Koepsell TD, Weiss NS, Heckbert SR et al. Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis. JAMA 1997; 277: Almgren T, Persson B, Wilhelmsen L, Rosengren A, Andersson OK. Stroke and coronary heart disease in treated hypertension a prospective cohort study over three decades. J Intern Med 2005; 257: Wilhelmsen L, Berglund G, Elmfeldt D, Tibblin G, Wedel H, Pennert K et al. The multifactor primary prevention trial in Göteborg, Sweden. Eur Heart J 1986; 7: Andersson OK, Almgren T, Persson B, Samuelsson O, Hedner T, Wilhelmsen L. Survival in treated hypertension: follow up study after two decades. BMJ 1998; 317: Clausen J, Jensen G. Blood pressure and mortality: an epidemiological survey with 10 years follow-up. J Hum Hypertens 1992; 6: Gudmundsson LS, Johannsson M, Thorgeirsson G, Sigfusson N, Sigvaldason H, Witteman JC. Hypertension control as predictor of mortality in treated men and women, followed for up to 30 years. Cardiovasc Drugs Ther 2005; 19: Casiglia E, Mazza A, Tikhonoff V, Pessina AC. Population-based studies improve outcome in hypertensive patients. Am J Hypertens 2002; 15: Bulpitt CJ, Palmer AJ, Fletcher AE, Beevers DG, Coles EC, Ledingham JG et al. Optimal blood pressure control in treated hypertensive patients. Report from the Department of Health Hypertension Care Computing Project (DHCCP). Circulation 1994; 90: Trafford JA, Horn CR, O Neal H, McGonigle R, Halford- Maw L, Evans R. Five year follow-up of effects of treatment of mild and moderate hypertension. Br Med J (Clin Res Ed) 1981; 282: Benetos A, Thomas F, Bean K, Gautier S, Smulyan H, Guize L. Prognostic value of systolic and diastolic blood pressure in treated hypertensive men. Arch Intern Med 2002; 162: Harms LM, Schellevis FG, van Eijk JT, Donker AJ, Bouter LM. Cardiovascular morbidity and mortality among hypertensive patients in general practice: the evaluation of long-term systematic management. J Clin Epidemiol 1997; 50: Vartiainen E, Jousilahti P, Alfthan G, Sundvall J, Pietinen P, Puska P. Cardiovascular risk factor changes in Finland, Int J Epidemiol 2000; 29: WHO MONICA Project Principal Investigators. The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. J Clin Epidemiol 1988; 41: Tuomilehto J, Vartiainen E, Sarti C, Nissinen A, Kastarinen M. Trends in hypertension, cardiovascular risk and stroke mortality in Finland. In: Bulpitt C (ed). Epidemiology of Hypertension, Hypertension Handbook. Elsevier Science B.V Amsterdam 2000, pp Gudmundsson LS, Johannsson M, Thorgeirsson G, Sigfusson N, Sigvaldason H, Witteman JC. Risk profiles and prognosis of treated and untreated hypertensive men and women in a population-based longitudinal study: the Reykjavik Study. J Hum Hypertens 2004; 18: Kastarinen MJ, Antikainen RL, Laatikainen TK, Salomaa VV, Tuomilehto JO, Nissinen AM et al. Trends in hypertension care in eastern and south-western Finland during J Hypertens 2006; 24: Kastarinen M, Laatikainen T, Salomaa V, Jousilahti P, Antikainen R, Tuomilehto J et al. Trends in lifestyle factors affecting blood pressure in hypertensive and normotensive Finns during J Hypertens 2007; 25: Kastarinen M, Tuomilehto J, Vartiainen E, Jousilahti P, Sundvall J, Puska P et al. Trends in lipid levels and hypercholesterolemia in hypertensive and normotensive Finnish adults from 1982 to J Intern Med 2000; 247: Kastarinen MJ, Nissinen AM, Vartiainen EA, Jousilahti PJ, Korhonen HJ, Puska PM et al. Blood pressure levels and obesity trends in hypertensive and normotensive Finnish population from 1982 to J Hypertens 2000; 18: Antikainen RL, Moltchanov VA, Chukwuma Sr C, Kuulasmaa KA, Marques-Vidal PM, Sans S et al. WHO MONICA Project. Trends in the prevalence, awareness, treatment and control of hypertension: the WHO MONICA Project. Eur J Cardiovasc Prev Rehabil 2006; 13: Kastarinen MJ, Salomaa VV, Vartiainen EA, Jousilahti PJ, Tuomilehto JO, Puska PM et al. Trends in blood pressure levels and control of hypertension in Finland from 1982 to J Hypertens 1998; 16: Burt VL, Cutler JA, Higgins M, Horan MJ, Labarthe D, Whelton P et al. Trends in the prevalence, awareness, treatment, and control of hypertension in the adult US population. Data from the Health Examination Surveys, 1960 to Hypertension 1995; 26: Ribacke M, Tibblin G, Rosengren A, Eriksson H. Is hypertension changing? Blood pressure development in cohorts of 50-year-old men between 1963 and Blood Press 1996; 5: Kastarinen MJ, Puska PM, Korhonen MH, Mustonen JN, Salomaa VV, Sundvall JE et al. Non-pharmacological treatment of hypertension in primary health care: a 2-year open randomized controlled trial of lifestyle intervention against hypertension in eastern Finland. J Hypertens 2002; 20: Yosefy C, Dicker D, Viskoper JR, Tulchinsky TH, Ginsberg GM, Leibovitz E et al. The Ashkelon Hypertension Detection and Control Program (AHDC Program): a community approach to reducing cardiovascular mortality. Prev Med 2003; 37: Guidelines Subcommittee European Society of Hypertension European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and 815

9 816 Treatment of High Blood Pressure. The JNC 7 Report. JAMA 2003; 289: Kiiskinen U, Vartiainen E, Puska P, Aromaa A. Longterm cost and life-expectancy consequences of hypertension. J Hypertens 1998; 16: Nilsson PM, Engström G, Hedblad B. Long-term predictors of increased mortality risk in screened men with new hypertension; the Malmo preventive project. J Hypertens 2008; 26: Staessen JA, Thijs L, Fagard R, Celis H, Birehäger WH, Bulpitt CJ et al. Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial. J Hypertens 2004; 22: Hansen TW, Jeppesen J, Rasmussen S, Ibsen H, Torp- Pedersen C. Ambulatory blood pressure monitoring and risk of cardiovascular disease: a population based study. Am J Hypertens 2006; 19: