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European Heart Journal Advance Access originally published online on November 2, 2007
European Heart Journal 2007 28(24):3059-3066; doi:10.1093/eurheartj/ehm501
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org

Joint effects of history of hypertension at baseline and type 2 diabetes at baseline and during follow-up on the risk of coronary heart disease

Gang Hu1,2,*, Pekka Jousilahti1,3 and Jaakko Tuomilehto1,2,4

1 Department of Health Promotion and Chronic Diseases Prevention, National Public Health Institute, Helsinki, Finland
2 Department of Public Health, University of Helsinki, Helsinki, Finland
3 Tampere School of Public Health, University of Tampere, Tampere, Finland
4 South Ostrobothnia Central Hospital, Seinäjoki, Finland

Received 26 February 2007; revised 17 September 2007; accepted 4 October 2007; online publish-ahead-of-print 2 November 2007.

* Corresponding author. Tel: +358 9 19127366; fax: +358 9 19127313. E-mail address: hu.gang{at}ktl.fi


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Funding
 References
 
Aims: To evaluate the joint associations of history of hypertension at baseline and type 2 diabetes at baseline and during follow-up on the incidence of coronary heart disease (CHD) and CHD mortality.

Methods and results: Study cohorts included 49 775 Finnish subjects aged 25–74 without history of CHD and stroke. The multivariable-adjusted hazard ratios (HRs) of CHD incidence were 1.25, 1.69, 1.25, 1.83, 1.85, 2.39, 2.15, and 3.31 (P-value for trend <0.001), respectively, among men with hypertension I (blood pressure 140–159/90–94 mmHg or using antihypertensive drugs at baseline but blood pressure <160/95 mmHg) only, with hypertension II (blood pressure ≥160/95 mmHg) only, with incident diabetes during follow-up only, with both hypertension I and incident diabetes, with both hypertension II and incident diabetes, with history of diabetes at baseline only, with both hypertension I and history of diabetes, and with both hypertension II and history of diabetes compared with men without either of these diseases. The corresponding HRs of CHD incidence among women were 1.52, 2.37, 2.45, 3.78, 4.56, 5.63, 6.10, and 7.41 (P-value for trend <0.001), respectively. The impact on CHD mortality associated with the different strata of hypertension and diabetes was almost the same or a little stronger compared with that on the CHD incidence.

Conclusion: Hypertension and type 2 diabetes increase the CHD risk independently, and their combination increases the risk dramatically, particularly in women.

Key Words: Coronary heart disease • Diabetes mellitus • Hypertension


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
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 References
 
Epidemiological studies have indicated that hypertension and type 2 diabetes are commonly associated conditions and their concordance is higher than that expected. Hypertension affects up to 40% or more of diabetic patients.1,2 High blood pressure has been found as one of the most important risk factors for coronary heart disease (CHD) in the general population3–5 and also in patients with type 2 diabetes.2,3,5,6 The role of type 2 diabetes as an independent risk factor for CHD has also been well established.3,5,7–9

Although a few studies exist about the joint prognostic effect of hypertension and type 2 diabetes on CHD risk in the general population,3,5 it is not fully known whether the increasing risk of CHD comes from the effect of hypertension or type 2 diabetes alone, or from the combined effect of both hypertension and type 2 diabetes. Moreover, most of these studies have presented the data on history of diabetes at baseline, and only one study has the data on incident diabetes during follow-up.10 The aim of this study is to evaluate the joint effects of hypertension of different stages at baseline and type 2 diabetes at baseline and during follow-up on the risk of CHD incidence and CHD mortality.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 Funding
 References
 
Subjects
Six independent cross-sectional population surveys were carried out in five geographic areas of Finland in 1972, 1977, 1982, 1987, 1992, and 1997.11 In 1972 and 1977, a randomly selected sample making up 6.6% of the population born between 1913 and 1947 was drawn. Since 1982, the sample was stratified by area, gender, and 10-year age group according to the World Health Organization (WHO) MONICA (MONItoring trends and determinants of CArdiovascular disease) protocol.12 The participation rate varied by year from 74–88%.11 The subjects included in the six surveys were 25–64 years of age, and the 1997 survey also included subjects aged 65 to 74 years. Subjects who participated in more than one survey were included only in the first survey cohort. The total sample size of the six surveys was 53 166. The final sample comprised 23,851 men and 25,924 women after excluding 2138 subjects with the history of CHD or stroke at baseline, 105 subjects with type 1 diabetes, and 1148 subjects with incomplete data on any required variables. The participants gave an informed consent (verbal 1972–1992 and signed 1997). These surveys were conducted according to the ethical rules of the National Public Health Institute, and the investigations were performed in accordance with the Declaration of Helsinki.

Baseline measurements
A self-administered questionnaire was sent to the participants to be completed at home. The questionnaire included questions on medical history, socioeconomic factors, physical activity, smoking habits, and alcohol consumption. Education level, measured as the total number of school years, was divided into birth cohort-specific tertiles. Physical activity included occupational, commuting, and leisure-time physical activity and were merged and regrouped into three categories: low, moderate, and high.13–16 On the basis of the responses, the participants were classified as never, ex-, and current smokers. Current smokers were categorized into those participants who smoked <20 or ≥20 cigarettes per day. Since questions on alcohol consumption were different between the first two surveys (1972 and 1977) and the latter surveys, the participants were categorized into abstainers and alcohol users. Family history of myocardial infarction was defined as a history of whose mothers or fathers were once diagnosed as myocardial infarction.

At the study centre, specially trained nurses measured height, weight, and blood pressure using the standardized protocol according to the WHO MONICA project.12 Height and weight were measured without shoes and with light clothing. Body mass index (BMI) was calculated by dividing weight in kilograms by the square of height in metres. Blood pressure was measured from the right arm after 5 min of sitting. After blood pressure measurement, a venous blood specimen was taken. Total cholesterol was determined by using Lieberman Burchard method in 1972 and 1977 and by an enzymatic method (CHOD-PAP, Boehringer MANNHEIM, Mannheim, Germany) since 1982. Because the enzymatic method gave 2.4% lower values than the Lieberman Burchard method, the values measured in 1972 and 1977 were corrected by this percentage. All samples were analysed in the same central laboratory at National Public Health Institute.

Assessment of hypertension at baseline and diabetes at baseline and during follow-up
Assessment of diabetes status was based on self-reporting and on the data of two nationwide registers. The National Hospital Discharge Register data included information on hospital discharge diagnosis from 1968 through the end of 2002. Data on diabetes medication were obtained from the National Social Insurance Institution's register on special reimbursement for glucose-lowering drugs from 1964 through the end of 2002. Glucose-lowering drugs prescribed by a physician are free of charge in Finland and are subject to approval of a physician who reviews each case history. The physician confirms the diagnosis of diabetes by applying the WHO criteria. All patients receiving free medication (either oral glucose-lowering agents or insulin) are entered into a register maintained by the National Social Insurance Institution. Subjects who reported having diabetes on the questionnaire, or who had had a hospital discharge diagnosis of diabetes, or the approval for free-of-charge medication for diabetes before the baseline survey were classified as having history of diabetes at baseline. Subjects who had the first hospital discharge diagnosis with diabetes, or the approval for free-of-charge medication for diabetes after the baseline survey were classified as having incident diabetes during follow-up.

Data on the initiation of antihypertensive drug treatment were also received from the records of the Social Insurance Institution's nationwide register on persons entitled to special reimbursement for antihypertensive drugs since 1964. Hypertension stage I was defined as systolic blood pressure 140–159 mmHg and/or diastolic blood pressure 90–94 mmHg, or using antihypertensive medicine according to the questionnaire or the approval of special reimbursement for antihypertensive drugs before the baseline survey but blood pressure at the survey examination <160 mmHg systolic and <95 mmHg diastolic. Hypertension stage II was defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥95 mmHg. The normotensive reference group was defined as systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg and without any antihypertensive drugs treatment at baseline.

Prospective follow-up
Follow-up information was based on the Finnish Hospital Discharge Register for non-fatal outcomes (hospitalized myocardial infarctions) and the Finnish Death Register for fatal outcomes (deaths due to CHD) by using social security numbers assigned to every citizen of Finland. The overall sensitivity of the diagnosis of myocardial infarction in the combined Finnish Hospital Discharge Register and the Causes of Death Register was 83%.17 Combined non-fatal myocardial infarction and fatal CHD cases were defined as the incident CHD events in the analysis. Follow-up data were available through 31 December 2004. The Eighth, Ninth and 10th Revisions of the International Classification of Diseases (ICD) were used to identify non-fatal myocardial infarction (410–411 and I21–I22, I24) and fatal cases of CHD (410–414 and I20–I25) cases.

Statistical analyses
The Cox proportional hazards model were used to estimate the hazard ratios (HRs) of CHD incidence and CHD mortality among participants in nine groups: subjects with neither hypertension nor diabetes, with hypertension I only, hypertension II only, incident diabetes during follow-up only, both hypertension I and incident diabetes, both hypertension II and incident diabetes, history of diabetes at baseline only, both hypertension I and history of diabetes, and subjects with both hypertension II and history of diabetes. The proportional hazards assumption in the Cox model was assessed with graphical methods and with models including time-by-covariate interactions.18 In general, all proportionality assumptions were appropriate. In addition, the association of blood pressure (as a continuous variable) with the risk of CHD was analysed stratifying by the diabetes status. The analyses were first carried out adjusting for age, and study year, and further also for BMI, total cholesterol, education, smoking, alcohol consumption, physical activity, and family history of myocardial infarction. A {chi}2 log-likelihood ratio test was carried out to test the significance of the interaction terms of hypertension and diabetes on coronary risk. Likelihood ratio test for interaction was also carried out to determine whether the effect of hypertension and diabetes on coronary risk was different in men and women. A P < 0.05 (two-sided) was considered as statistically significant. All statistical analyses were performed with SPSS for Windows 15.0 (SPSS Inc., III, Chicago, USA).


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 Funding
 References
 
General characteristics of the study population at baseline are presented in Table 1. During a median follow-up of 21.5 years (12.8 and 27.8 years for the 25th and the 75th quartiles, respectively), 5074 incident CHD events were recorded, of which 3134 were fatal.


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  		Table 1 Baseline characteristics of study subjects by sex

 
When blood pressure was used as a continuous variable, multivariable-adjusted (age, study year, BMI, total cholesterol, education, smoking, alcohol drinking, physical activity, and family history of myocardial infarction) HRs of CHD incidence among men were 1.22 (95% CI 1.18–1.26) for a 20 mmHg increment in systolic blood pressure and 1.18 (95% CI 1.15–1.22) for a 10 mmHg increment in diastolic blood pressure (Table 2). The corresponding multivariable-adjusted HRs among women were 1.26 (95% CI 1.21–1.30) and 1.23 (95% CI 1.18–1.28). The association of blood pressure with the risk of CHD was a little stronger among non-diabetic subjects than subjects with diabetes both during follow-up and at baseline. CHD incidence was increased by 23% (95% CI 1.10–1.37) in men with incident diabetes during follow-up and by 90% (95% CI 1.59–2.27) in men with history of diabetes at baseline compared with non-diabetic men. In women, CHD incidence was increased by 2.04 times (95% CI 1.80–2.30) and 3.7 times (95% CI 3.02–4.53), respectively.


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  		Table 2 Hazard ratios for coronary heart disease incidence and mortality according to continuous blood pressure levels or the status of diabetesa

 
Compared with men and women without hypertension or diabetes, age- and study year-adjusted HRs of CHD incidence associated with hypertension I only, with hypertension II only, with incident diabetes during follow-up only, with both hypertension I and incident diabetes, with both hypertension II and incident diabetes, with history of diabetes at baseline only, with both hypertension I and history of diabetes, and with both hypertension II and history of diabetes were 1.35, 1.98, 1.45, 2.25, 2.43, 2.54, 2.28, and 3.65 (P-value for trend <0.001) in men, and 1.61, 2.61, 2.86, 4.20, 5.32, 5.88, 6.65, and 8.66 (P-value for trend <0.001) in women, respectively (Table 3). The corresponding HRs of coronary mortality were 1.54, 2.44, 1.28, 1.82, 2.60, 3.27, 3.23, and 4.81 (P-value for trend <0.001) in men and 1.70, 3.02, 3.49, 3.78, 6.40, 7.92, 10.3, and 13.3 (P-value for trend <0.001) in women, respectively (Table 4). Further adjustments for other risk factors did not appreciably change these risk estimates. The interaction terms of hypertension and diabetes on both CHD incidence ({chi}2 = 7.43 in men and 6.79 in women, 4 d.f., both P > 0.1) and CHD mortality ({chi}2 = 2.32 in men and 5.38 in women, 4 d.f., both P > 0.1) were not statistically significant, indicating that these two factors operated independently for the CHD risk.


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  		Table 3 Hazard ratios for coronary heart disease incidence according to status of hypertension and diabetes

 

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  		Table 4 Hazard ratios for coronary heart disease mortality according to status of hypertension and diabetes

 
Compared with men and women without hypertension and diabetes, the relative risks of incident CHD and CHD mortality were higher in women than in men with any combination of hypertension and diabetes. This sex difference was, however, statistically significant for only CHD incidence among subjects with hypertension I only ({chi}2 = 4.31, 1 d.f., P < 0.05), and for both CHD incidence and CHD mortality among subjects with hypertension II only ({chi}2 = 20.46 and 9.0, 1 d.f., P < 0.001 and P < 0.005), with incident diabetes during follow-up only ({chi}2 = 8.47 and 10.36, 1 d.f., both P < 0.005), with both hypertension I and incident diabetes ({chi}2 = 23.16 and 17.44, 1 d.f., both P < 0.001), with both hypertension II and incident diabetes ({chi}2 = 50.46 and 34.64, 1 d.f., both P < 0.001), with history of diabetes at baseline only ({chi}2 = 6.02 and 4.15, 1 d.f., P < 0.025 and P < 0.05), with both hypertension I and history of diabetes ({chi}2 = 17.91 and 14.51, 1 d.f., both P < 0.001), and with both hypertension II and history of diabetes ({chi}2 = 16.85 and 17.07, 1 d.f., both P < 0.001).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Funding
 References
 
This study indicated that both hypertension and type 2 diabetes were independently associated with an increased risk of the incidence of CHD and CHD mortality. Blood pressure was associated with the risk of CHD in a similar fashion both in diabetic and non-diabetic subjects, but the absolute rates were higher in diabetic patients. The highest risk of an incident CHD event, and in particular of CHD death, was found among subjects who had both history of hypertension and history of diabetes; it is probably due to a longer duration of these conditions compared with people whose diabetes was diagnosed during the follow-up.

High blood pressure is one of the most important risk factors for CHD in all ethnic groups.4 The association between blood pressure and CHD mortality is strong and direct, and the absolute risk of CHD mortality associated with high blood pressure increases with age.4 However, most studies of hypertension and CHD risk have not stratified for the diabetes status or have used only history of diabetes as a confounder in analyses. We found that this direct association between blood pressure and the CHD risk was consistent among both diabetic and non-diabetic subjects. Several studies have demonstrated that hypertension, or an increase in systolic blood pressure, is independently associated with an increased risk of CHD in the diabetic patients.2,3,5,6 It is also known that hypertension predicts the development of type 2 diabetes.19 Prevalent type 2 diabetes is a well-established risk factor for CHD3,5,7–9 Epidemiological studies have indicated that patients with type 2 diabetes have a two to four times higher risk of CHD mortality than those without diabetes,3,5,7–9,20 and diabetic women show a higher relative risk for cardiovascular disease than diabetic men.9,20,21 An important question is, however, to what extent asymptomatic diabetes, new-onset diabetes during follow-up, and impaired glucose tolerance are related to the risk of CHD.8,10,20 It has been shown that about half of the type 2 diabetes patients and most of the people with impaired glucose tolerance are unaware of their condition, if not tested for glucose tolerance.22 Also, it is known that diabetes may remain undiagnosed for over 10 years,23 and during this period, hyperglycaemia (including asymptomatic diabetes, new-onset diabetes during follow-up, and impaired glucose tolerance) may cause cardiovascular disease.8,10,20 Furthermore, although hypertension is very common in patients with type 2 diabetes,1 only a few studies assessed the joint effect of hypertension and type 2 diabetes on the CHD risk in the general population. Our results suggest that, in order to reduce CHD risk, it is necessary to consider carefully the treatment strategies based on the individual disease status, including both hypertension and diabetes and their combination. Because we did not have data on the active management of hypertension and diabetes during the follow-up, our predictions may underestimate the risk since potential treatment benefits were not taken into account.

Recently, clinical trials have shown that pharmacological treatments of hypertension are efficient ways to prevent CHD in hypertensive patients.24,25 A meta-analysis based on 18 randomized trials found that low-dose diuretic therapy was effective in preventing CHD mortality.24 For diabetic patients, blood pressure lowering therapy seems to offer a greater reduction in the risk of macrovascular disease than do interventions for blood glucose control.26,27 This is probably in part due to the fact that currently we have more efficient tools to lower blood pressure than to control hyperglycaemia. In antihypertensive therapy, the recent guidelines have recommended to control both systolic and diastolic blood pressures, although prior to the results from trials on isolated systolic hypertension28,29 the emphasis was on diastolic pressure. In anti-diabetic therapy, the emphasis is still largely on the control of fasting hyperglycaemia, not post-prandial (post-challenge) hyperglycaemia. Observational studies have, however, provided undisputed evidence that cardiovascular risk largely depends on post-prandial (post-challenge) glucose, not on fasting glucose.8 This may be another reason for poor impact of anti-diabetic treatment on cardiovascular risk. Several clinical trials have demonstrated that adequate control of hypertension attenuates the risk of CHD in hypertensive diabetic patients,24,25,30,31 even to the level of non-diabetic patients.25

There are several strengths and limitations in our study. We have a unique possibility to stratify not only for the baseline but also for follow-up status of diabetes. The number of participants was large and from a homogeneous population. The median follow-up, 21.5 years, was long and resulted in a very large number of CHD events. Because of computerized register linkage, the event ascertainment was complete. A limitation of our study was that we did not carry out either fasting glucose test or glucose tolerance test at the baseline. Therefore, we have missed cases of asymptomatic diabetes at baseline, but many of them were ascertained as incident cases of diabetes during the follow-up. Another limitation was that we did not have data on individual drugs used for the treatments of hypertension and diabetes, but with such a long duration of the observational study it would be almost impossible to reveal effects due to specific pharmacological agents, since their use has varied drastically over time in most if not all of hypertensive and diabetic patients. Finally, we cannot completely exclude the effects of residual confounding due to measurement errors in the assessment of confounding factors or some unmeasured dietary, social, and other factors.

In conclusion, our study confirmed that both hypertension and type 2 diabetes increased the risk of CHD independently, but in people who had both of them together, the risk increased dramatically. Since hypertension and type 2 diabetes often occur concomitantly, it is possible that part of the risk of CHD assumed to be related to high blood pressure may primarily be due to undiagnosed disorders in glucose metabolism since blood pressure values are recorded much more often than glucose values, in particular post-challenge glucose. This has to be assessed in studies where adequate data also on glucose tolerance have been collected.

Conflict of interest: none declared.


   Funding
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
References
 
This study was supported by grants from the Finnish Academy (grant 118065), and the Finnish Foundation for Cardiovascular Research.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Funding
 References
 

  1. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care (2003) 26((Suppl. 1)):S80–S82.[CrossRef][Medline]
  2. Hu G, Jousilahti P, Barengo NC, Qiao Q, Lakka TA, Tuomilehto J. Physical activity, cardiovascular risk factors, and mortality among Finnish adults with diabetes. Diabetes Care (2005) 28:799–805.[Abstract/Free Full Text]
  3. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care (1993) 16:434–444.[Abstract]
  4. 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) 360:1903–1913.[CrossRef][ISI][Medline]
  5. Folsom AR, Chambless LE, Duncan BB, Gilbert AC, Pankow JS. Prediction of coronary heart disease in middle-aged adults with diabetes. Diabetes Care (2003) 26:2777–2784.[Abstract/Free Full Text]
  6. Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, Holman RR. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ (1998) 316:823–828.[Abstract/Free Full Text]
  7. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med (1998) 339:229–234.[Abstract/Free Full Text]
  8. DECODE Study Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2 h diagnostic criteria. Arch Intern Med (2001) 161:397–405.[Abstract/Free Full Text]
  9. Hu G, Jousilahti P, Qiao Q, Katoh S, Tuomilehto J. Sex differences in cardiovascular and total mortality among diabetic and non-diabetic individuals with or without history of myocardial infarction. Diabetologia (2005) 48:856–861.[CrossRef][ISI][Medline]
  10. Smith NL, Barzilay JI, Kronmal R, Lumley T, Enquobahrie D, Psaty BM. New-onset diabetes and risk of all-cause and cardiovascular mortality: the Cardiovascular Health Study. Diabetes Care (2006) 29:2012–2017.[Abstract/Free Full Text]
  11. Vartiainen E, Jousilahti P, Alfthan G, Sundvall J, Pietinen P, Puska P. Cardiovascular risk factor changes in Finland, 1972-1997. Int J Epidemiol (2000) 29:49–56.[Abstract/Free Full Text]
  12. Pajak A, Kuulasmaa K, Tuomilehto J, Ruokokoski E. Geographical variation in the major risk factors of coronary heart disease in men and women aged 35–64 years. The WHO MONICA Project. World Health Stat Q (1988) 41:115–140.[Medline]
  13. Hu G, Qiao Q, Silventoinen K, Eriksson JG, Jousilahti P, Lindstrom J, Valle TT, Nissinen A, Tuomilehto J. Occupational, commuting, and leisure-time physical activity in relation to risk for type 2 diabetes in middle-aged Finnish men and women. Diabetologia (2003) 46:322–329.[ISI][Medline]
  14. Hu G, Eriksson J, Barengo NC, Lakka TA, Valle TT, Nissinen A, Jousilahti P, Tuomilehto J. Occupational, commuting, and leisure-time physical activity in relation to total and cardiovascular mortality among Finnish subjects with type 2 diabetes. Circulation (2004) 110:666–673.[Abstract/Free Full Text]
  15. Hu G, Sarti C, Jousilahti P, Silventoinen K, Barengo NC, Tuomilehto J. Leisure time, occupational, and commuting physical activity and the risk of stroke. Stroke (2005) 36:1994–1999.[Abstract/Free Full Text]
  16. Hu G, Tuomilehto J, Borodulin K, Jousilahti P. The joint associations of occupational, commuting, and leisure-time physical activity, and the Framingham risk score on the 10-year risk of coronary heart disease. Eur Heart J (2007) 28:492–498.[Abstract/Free Full Text]
  17. Pajunen P, Koukkunen H, Ketonen M, Jerkkola T, Immonen-Raiha P, Karja-Koskenkari P, Mahonen M, Niemela M, Kuulasmaa K, Palomaki P, Mustonen J, Lehtonen A, Arstila M, Vuorenmaa T, Lehto S, Miettinen H, Torppa J, Tuomilehto J, Kesaniemi YA, Pyorala K, Salomaa V. The validity of the Finnish Hospital Discharge Register and Causes of Death Register data on coronary heart disease. Eur J Cardiovasc Prev Rehabil (2005) 12:132–137.[CrossRef][ISI][Medline]
  18. Cox DR. Regression models and life tables (with discussion). J R Stat Soc B (1972) 34:187–220.
  19. Gress TW, Nieto FJ, Shahar E, Wofford MR, Brancati FL. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. N Engl J Med (2000) 342:905–912.[Abstract/Free Full Text]
  20. Hu G. Gender difference in all-cause and cardiovascular mortality related to hyperglycaemia and newly-diagnosed diabetes. Diabetologia (2003) 46:608–617.[ISI][Medline]
  21. Kanaya AM, Grady D, Barrett-Connor E. Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus: a meta-analysis. Arch Intern Med (2002) 162:1737–1745.[Abstract/Free Full Text]
  22. DECODE Study Group. Age- and sex-specific prevalences of diabetes and impaired glucose regulation in 13 European cohorts. Diabetes Care (2003) 26:61–69.[Abstract/Free Full Text]
  23. Eeley EA, Stratton IM, Hadden DR, Turner RC, Holman RR. UKPDS 18: estimated dietary intake in type 2 diabetic patients randomly allocated to diet, sulphonylurea or insulin therapy. UK Prospective Diabetes Study Group. Diabet Med (1996) 13:656–662.[CrossRef][ISI][Medline]
  24. Psaty BM, Smith NL, Siscovick DS, Koepsell TD, Weiss NS, Heckbert SR, Lemaitre RN, Wagner EH, Furberg CD. Health outcomes associated with antihypertensive therapies used as first-line agents. A systematic review and meta-analysis. JAMA (1997) 277:739–745.[Abstract]
  25. Tuomilehto J, Rastenyte D, Birkenhager WH, Thijs L, Antikainen R, Bulpitt CJ, Fletcher AE, Forette F, Goldhaber A, Palatini P, Sarti C, Fagard R. Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators. N Engl J Med (1999) 340:677–684.[Abstract/Free Full Text]
  26. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. Jama (2003) 289:2560–2572.[Abstract/Free Full Text]
  27. Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R, Tuttle K, Douglas J, Hsueh W, Sowers J. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis (2000) 36:646–661.[ISI][Medline]
  28. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA (1991) 265:3255–3264.[Abstract]
  29. Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O'Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet (1997) 350:757–764.[CrossRef][ISI][Medline]
  30. Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet (1998) 351:1755–1762.[CrossRef][ISI][Medline]
  31. The ALLHAT Officers and Coordinators for the Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA (2002) 288:2981–2997.[Abstract/Free Full Text]

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