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This study investigates whether the interaction between angiotensin-converting enzyme (ACE) inhibitors or beta-blockers and the ACE insertion/deletion (I/D) polymorphism or angiotensin receptor II type 1 (AGTR1) 573C/T polymorphism modifies the risk of myocardial infarction (MI) or stroke. In total, 4097 subjects with hypertension were included in this study. The drug-gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model. The risk of MI was reduced in current users of ACE inhibitors with the AGTR1 573CT or CC genotype compared to ACE inhibitors with the AGTR1 573TT genotype (synergy index (SI):0.32; 95% confidence interval (CI): 0.14-0.70). No significant drug-gene interaction was found on the risk of stroke (SI:0.82; 95% CI: 0.44-1.52) or in beta-blocker users. Also, no significant drug-gene interaction was found with the ACE I/D polymorphism. In conclusion, subjects with at least one copy of the AGTR1 573C allele might have more benefit from ACE inhibitor therapy.

This study investigates whether the interaction between diuretics and alpha-adducin (ADD1) G460W or G-protein beta3-subunit (GNB3) rs2301339 polymorphism modifies the risk of myocardial infarction (MI) or stroke. Data were used from the Rotterdam Study. The drug-gene interaction was determined with a Cox proportional hazard model with adjustment for each drug class as time-dependent covariates. The risk of MI in current users of low-ceiling diuretics with one or two copies of the ADD1 W-allele (hazard ration (HR)=0.92) was similar compared to the expected joint effect of the W-allele and low-ceiling diuretics on a multiplicative scale (1.04 x 0.90=0.94) (synergy index (SI):0.99; 95% confidence interval (CI): 0.43-2.27). No drug-gene interaction was found on the risk of stroke (SI:0.66; 95% CI:0.43-1.27). In addition, a trend towards an interaction was found between current use and the GNB3 rs230119 G/A polymorphism on the risk of MI (SI: 0.51; 95% CI: 0.23-1.15), whereas no interaction on the risk of stroke was found (SI: 0.84; 95% CI: 0.46-1.56).

Objective: To investigate the relationship between unrecognized myocardial infarction and the risk of stroke in a population-based cohort study., Methods: We followed 6,439 participants from the Rotterdam Study for stroke until January 2002. Participants were free from stroke, and presence of myocardial infarction was assessed at baseline (1990-1993). We calculated hazard ratios of stroke for persons with unrecognized or recognized myocardial infarction compared with persons without myocardial infarction. Analyses were adjusted for age, sex, and cardiovascular risk factors., Results: In 52,915 person-years of follow-up, 505 strokes occurred. Recognized myocardial infarction was only borderline associated with an increased risk of stroke. Unrecognized myocardial infarction increased the risk of stroke by 76% (age- and sex-adjusted hazard ratio 1.76, 95% CI 1.31 to 2.37). Stratification by sex showed that the increased risk was only found in men (hazard ratio for men 2.53, 95% CI 1.68 to 3.81; hazard ratio for women 1.27, 95% CI 0.82 to 1.96). After adjusting for cardiovascular risk factors at baseline, the risk remained significantly increased in men (hazard ratio for stroke 2.13, 95% CI 1.35 to 3.36). Subtyping of strokes revealed that unrecognized myocardial infarction was particularly associated with cortical ischemic strokes (hazard ratio for men 3.57, 95% CI 1.79 to 7.12)., Conclusions: Men with unrecognized myocardial infarction have an increased risk of stroke.

It is unclear how the APOE genotype contributes to the incidence of vascular diseases and dementia. In a population-based sample (n = 6,852) with complete follow-up, APOE was weakly associated with myocardial infarction and not related with stroke. In the absence of epsilon4, the incidence of dementia would be 25.8% lower; in the absence of epsilon2/epsilon3, 2.8% higher. Risk estimates of dementia, specified for age, sex, and APOE, are provided for counseling. APOE is not strongly related to vascular diseases, but contributes substantially to dementia incidence.

Aims: Available data are insufficient to determine the relation between coronary calcification and coronary events in the general population. We cross-sectionally examined the association between coronary calcification and myocardial infarction in the prospective Rotterdam Coronary Calcification Study., Methods and Results: From 1997 onwards, subjects were invited for electron-beam computed tomography scanning to detect coronary calcification. The study was embedded in the population-based Rotterdam Study. Calcifications were quantified in a calcium score according to Agatston's method. Calcium scores were available for 2,013 participants with a mean age of 71 years (standard deviation, 5.7 years). A history of myocardial infarction prior to scanning was present in 229 subjects. Compared to subjects in the lowest calcium score category (0-100), the age-adjusted odds ratio for myocardial infarction in subjects in the highest calcium score category (above 2,000) was 7.7 (95% confidence interval, 4.1-14.5) for men, and 6.7 (95% confidence interval, 2.4-19.1) for women. Additional adjustment for cardiovascular risk factors only slightly altered the estimates. The association was observed across all age subgroups, i.e. also in subjects of 70 years and older., Conclusion: A strong and graded association was found between coronary calcification and myocardial infarction. The association remained at high ages., (Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)

Background and Purpose: We determined the contribution of common carotid intima-media thickness (IMT) in the prediction of future coronary heart disease and cerebrovascular disease when added to established risk factors., Methods: We used data from a nested case-control study comprising 374 subjects with either an incident stroke or a myocardial infarction and 1496 controls. All subjects were aged 55 years and older and participated in the Rotterdam Study. Mean follow-up was 4.2 years (range, 0.1 to 6.5 years). We evaluated which correlates of coronary heart disease and cerebrovascular disease contribute to the prediction of either a new incident myocardial infarction or a stroke. Logistic regression modeling and the area under the receiver operating characteristic curve (ROC area) were used to quantify the predictive value of the established risk factors and the added value of IMT., Results: The ROC area of a model with age and sex only was 0.65 (95% CI, 0.62 to 0.69). Independent risk factors were previous myocardial infarction and stroke, diabetes mellitus, smoking, systolic blood pressure, diastolic blood pressure, and total and HDL cholesterol levels. These risk factors increased the ROC area from 0.65 to 0.72 (95% CI, 0.69 to 0.75). This model correctly predicted 17% of all subjects with coronary heart disease and cerebrovascular disease. When common carotid IMT was added to the previous model, the ROC area increased to 0.75 (95% CI, 0.72 to 0.78). When only the IMT measurement was used, the ROC area was 0.71 (95% CI, 0.68 to 0.74), and 14% of all subjects were correctly predicted. There was no difference in ROC area when different measurement sites were used., Conclusions: Adding IMT to a risk function for coronary heart disease and cerebrovascular disease does not result in a substantial increase in the predictive value when used as a screening tool.

Evidence is accumulating that low levels of IGF-I play a role in the pathogenesis of type 2 diabetes and cardiovascular diseases. We examined the role of a genetic polymorphism in the promoter region of the IGF-I gene in relation to circulating IGF-I levels and growth measured as body height, and we studied the relationship of this polymorphism with type 2 diabetes and myocardial infarction. The relation between the IGF-I polymorphism and body height was assessed in a population-based sample of 900 subjects from the Rotterdam Study. Within each genotype stratum, 50 subjects were randomly selected for a study of the relation of this polymorphism with serum IGF-I levels. To assess the risk for type 2 diabetes, we studied 220 patients and 596 normoglycemic control subjects. For myocardial infarction, 477 patients with evidence of myocardial infarction on electrocardiogram and 808 control subjects were studied. A 192-bp allele was present in 88% of the population, suggesting that this is the wild-type allele from which all other alleles originated. Body height was, on average, 2.7 cm lower (95% CI for difference -4.6 to -0.8 cm, P = 0.004), and serum IGF-I concentrations were 18% lower (95% CI for difference -6.0 to -1.3 mmol/l, P = 0.003) in subjects who did not carry the 192-bp allele. In noncarriers of the 192-bp allele, an increased relative risk for type 2 diabetes (1.7 [95% CI 1.1-2.7]) and for myocardial infarction (1.7 [95% CI 1.1-2.5]) was found. In patients with type 2 diabetes, the relative risk for myocardial infarction in subjects without the 192-bp allele was 3.4 (95% CI 1.1-11.3). Our study suggests that a genetically determined exposure to relatively low IGF-I levels is associated with an increased risk for type 2 diabetes and myocardial infarction.

Objectives: To estimate the health effects of postmenopausal hormone therapy used for 10 or 20 years in a population of intermediate cardiovascular risk., Design: Using existing estimates of the effect of hormone therapy on rates of myocardial infarction, hip fracture and breast cancer, a proportional multistage life table was generated to calculate the effects of use for 10 and 20 years in a synthetic cohort of Dutch women aged 55 with an average and a high-risk profile for cardiovascular disease., Results: A woman of the general population who starts hormone therapy at age 55 for 10 years can prolong her life by 1 month and may postpone the occurrence of first incidence of one of the diseases under consideration by 2.4 months. One excess breast cancer case is likely to occur per 5-6 averted cases of first myocardial infarction or hip fracture. If she prolongs her use to 20 years, the gain of life expectancy and disease-free life expectancy is doubled. The risk-benefit ratio worsens to one extra breast cancer per 3-4 averted cases of the preventable diseases. For a woman with a high-risk profile, the gains in health are about twice as high as for her counterpart in the general population, and her risk-benefit ratio is also more favourable. Yet, the risk-benefit ratio still worsens for 20 as compared with 10 years of use., Conclusions: Women from the general population in the Netherlands and similar populations can achieve only a modest gain in life expectancy by using hormones during 10 or 20 years following menopause. This is a consequence of the low incidence of myocardial infarction and hip fracture and the relatively high incidence of breast cancer before the age of 75. Women at increased cardiovascular risk can benefit more from hormone therapy. But even amongst these women, the risk of breast cancer incurred with long-term use offsets much of the benefit that could accrue from changing the risk of heart disease and hip fracture.

Background: Overt hypothyroidism has been found to be associated with cardiovascular disease. Whether subclinical hypothyroidism and thyroid autoimmunity are also risk factors for cardiovascular disease is controversial., Objective: To investigate whether subclinical hypothyroidism and thyroid autoimmunity are associated with aortic atherosclerosis and myocardial infarction in postmenopausal women., Design: Population-based cross-sectional study., Setting: A district of Rotterdam, The Netherlands., Participants: Random sample of 1149 women (mean age +/- SD, 69.0 +/- 7.5 years) participating in the Rotterdam Study., Measurements: Data on thyroid status, aortic atherosclerosis, and history of myocardial infarction were obtained at baseline. Subclinical hypothyroidism was defined as an elevated thyroid-stimulating hormone level (>4.0 mU/L) and a normal serum free thyroxine level (11 to 25 pmol/L [0.9 to 1.9 ng/dL]). In tests for antibodies to thyroid peroxidase, a serum level greater than 10 IU/mL was considered a positive result., Results: Subclinical hypothyroidism was present in 10.8% of participants and was associated with a greater age-adjusted prevalence of aortic atherosclerosis (odds ratio, 1.7 [95% CI, 1.1 to 2.6]) and myocardial infarction (odds ratio, 2.3 [CI, 1.3 to 4.0]). Additional adjustment for body mass index, total and high-density lipoprotein cholesterol level, blood pressure, and smoking status, as well as exclusion of women who took beta-blockers, did not affect these estimates. Associations were slightly stronger in women who had subclinical hypothyroidism and antibodies to thyroid peroxidase (odds ratio for aortic atherosclerosis, 1.9 [CI, 1.1 to 3.6]; odds ratio for myocardial infarction, 3.1 [CI, 1.5 to 6.3]). No association was found between thyroid autoimmunity itself and cardiovascular disease. The population attributable risk percentage for subclinical hypothyroidism associated with myocardial infarction was within the range of that for known major risk factors for cardiovascular disease., Conclusion: Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women.

Objective: To study the association between blood pressure and risk of myocardial infarction in elderly subjects., Design: Prospective cohort study., Setting: The Rotterdam Study, a Dutch population-based study., Participants: 6004 men and women aged > or = 55 years., Main Outcome Measures: Fatal or non-fatal myocardial infarction (n = 190) during a 4-year follow-up., Results: After excluding participants using blood pressure-lowering medication and participants with a history of myocardial infarction, increasing levels of systolic blood pressure (SBP) were associated with increasing risk of first myocardial infarction (P for trend < 0.0001). The relative risk (RR) for an SBP of 160 mmHg or higher was 5.7 (95% confidence interval (CI) 1.9-17.1) compared with an SBP below 120 mmHg. Increasing diastolic blood pressure (DBP) was also associated with increasing risk of first myocardial infarction, with the RR reaching 2.5 (95% CI 1.4-4.5) in subjects with values of 80-90 mmHg compared with values below 70 mmHg (P for trend < 0.05). Analyses in subjects aged 70 years and over showed that the positive associations between SBP and DBP and risk of first myocardial infarction remained at older age., Conclusion: These findings in a relatively healthy cohort of elderly subjects do not provide evidence for a J- or U-shaped relation between SBP and DBP and risk of first myocardial infarction. They suggest that the risk of first myocardial infarction increases with increasing level of systolic and diastolic blood pressure and that this relationship persists into older age.

Objective: To investigate the associations of serum total and HDL cholesterol with the risk of myocardial infarction in men and women of 55 years and over., Design: The Rotterdam Study is a population-based prospective cohort study. In total 2453 men and 3553 women of 55 years and older were included in this study. The mean duration of follow-up was 4 years., Main Outcome Measures: Relative risks were estimated with Cox's proportional-hazard analysis. Cholesterol was analysed as a continuous variable and in sex-specific quartiles., Results: In subjects aged 55 years and older the relative risk of myocardial infarction was 1.9 in men (95% confidence interval 1.1-3.3) and 3.2 in women (1.5-6.4) in the highest compared to the lowest serum total cholesterol quartile (Q4 vs. Q1). In men and women of 70 years and older, total cholesterol remained an important risk factor for myocardial infarction (Q4 vs. Q1 relative risk 3.2; 1.3-7.7 and 2.9; 1.3-6.6, respectively). For HDL cholesterol, the relative risk in the highest compared to the lowest quartile (Q4 vs. Q1) was 0.5 in men (0.3-0.9) and 0.4 in women (0.2-0.9). HDL cholesterol was a weaker predictor in men after the age of 70 (Q4 vs. Q1 0.8; 0.3-2.1). In women of 70 years and older the relative risk was also not significant (Q4 vs. Q1 0.6; 0.3-1.3), although the trend over the quartiles was still significant., Conclusion: Serum total cholesterol remains an important risk factor for myocardial infarction in men and women aged 70 years and older, whilst HDL cholesterol at older age remains important in women only.

Background: Elevated body iron stores have been suggested to be a risk factor for ischemic heart disease., Objective: We examined whether elevated serum ferritin concentrations, other indicators of iron status, and dietary iron affected the incidence of myocardial infarction (MI) in an elderly population., Design: A nested, case-control study of 60 patients who had their first MI and 112 age- and sex-matched control subjects embedded in the population-based cohort of the Rotterdam Study., Results: The age- and sex-adjusted risk of MI for subjects with serum ferritin concentrations > or = 200 microg/L was 1.82 (95% CI: 0.90, 3.69; P = 0.096). The odds ratio (OR) was 1.26 (95% CI: 0.98, 1.64; P = 0.078) for the highest tertile of serum ferritin and was only slightly altered in a multivariate model. Risk of MI associated with the highest tertile of ferritin was most evident in current or former smokers (OR: 1.68; 95% CI: 1.17, 2.47; P for trend = 0.008) and in subjects with hypercholesterolemia (OR: 1.43; 95% CI: 0.99, 2.11; P for trend = 0.056) or diabetes (OR: 2.41; 95% CI: 1.12, 7.67; P for trend = 0.027). No association with risk of MI was observed for tertiles of serum iron, serum transferrin, or total dietary iron. For dietary heme iron, risk of MI was significantly increased in a multivariate model in which dietary energy, fat, saturated fat, and cholesterol were adjusted for (OR: 4.01; 95% CI: 1.17, 15.87; P for trend = 0.031)., Conclusion: In the presence of other risk factors, serum ferritin may adversely affect ischemic heart disease risk in the elderly.

Free iron has been implicated in lipid peroxidation and ischemic myocardial damage, and it has been suggested that iron is an independent risk factor for myocardial infarction. The authors investigated whether dietary iron is associated with an increased risk of fatal and nonfatal myocardial infarction in the Rotterdam Study, a community-based prospective cohort study of 7,983 elderly subjects in Rotterdam, the Netherlands. The study sample consisted of 4,802 participants who at baseline had no known history of myocardial infarction and for whom dietary data were available. From 1990 to 1996, 124 subjects had a myocardial infarction. No association was observed between total iron intake and risk of myocardial infarction after adjustment for age and sex (relative risk for the highest vs. the lowest tertile of intake = 0.89, 95% confidence interval (CI) 0.55-1.45, p for trend = 0.640). Heme iron intake was positively associated with risk of myocardial infarction (relative risk for the highest vs. the lowest tertile of intake = 1.83, 95% CI 1.16-2.91, p for trend = 0.008) after adjustment for age and sex, and this association persisted after multivariate adjustment (relative risk = 1.86, 95% CI 1.14-3.09, p for trend = 0.010). A distinction between fatal and nonfatal cases of myocardial infarction indicated that the association of heme iron with myocardial infarction was more pronounced in fatal cases. The results suggest that a high dietary heme iron intake is related to an increased risk of myocardial infarction and that it may specifically affect the rate of fatality from myocardial infarction.

Background: Epidemiologic studies have shown dietary antioxidants to be inversely correlated with ischemic heart disease., Objective: We investigated whether dietary beta-carotene, vitamin C, and vitamin E were related to the risk of myocardial infarction (MI) in an elderly population., Design: The study sample consisted of 4802 participants of the Rotterdam Study aged 55-95 y who were free of MI at baseline and for whom dietary data assessed by a semiquantitative food frequency questionnaire were available. During a 4-y follow-up period, 124 subjects had an MI. The association between energy-adjusted beta-carotene, vitamin C, and vitamin E intakes and risk of MI was examined by multivariate logistic regression., Results: Risk of MI for the highest compared with the lowest tertile of beta-carotene intake was 0.55 (95% CI: 0.34, 0.83; P for trend = 0.013), adjusted for age, sex, body mass index, pack-years, income, education, alcohol intake, energy-adjusted intakes of vitamin C and E, and use of antioxidative vitamin supplements. When beta-carotene intakes from supplements were considered, the inverse relation with risk of MI was slightly more pronounced. Stratification by smoking status indicated that the association was most evident in current and former smokers. No association with risk of MI was observed for dietary vitamin C and vitamin E., Conclusion: The results of this observational study in the elderly population of the Rotterdam Study support the hypothesis that high dietary beta-carotene intakes may protect against cardiovascular disease. We did not observe an association between vitamin C or vitamin E and MI.

Serum Cu and caeruloplasmin levels have been suggested to be independent risk factors for CHD operating through oxidative modification of LDL. However, given its function as an acute-phase protein, the question has been raised whether an elevated caeruloplasmin level is not merely an indicator of inflammation. In the current study, we investigated whether serum caeruloplasmin was associated with subsequent myocardial infarction, taking into account indices of inflammation. The study population consisted of 210 cases of first myocardial infarction and controls, frequency-matched on age (5-year categories) and sex, selected from the population-based cohort of the Rotterdam Study. Serum caeruloplasmin levels were significantly elevated in cases of myocardial infarction compared with controls (510 (SD 110) v. 470 (SD 100) mg/l; P = 0.007). Risk of myocardial infarction for the highest compared with the lowest quartile of caeruloplasmin was 2.46 (95% CI 1.04, 6.00; Ptrend = 0.043) after adjustment for age, sex, BMI, pack-years smoked, serum cholesterol, systolic blood pressure, and income. The relative risk was most evident in current smokers. Adjustment for C-reactive protein and leucocyte count reduced the excess risk by 33%. This suggests that a substantial part of the observed association between serum caeruloplasmin and CHD may be attributed to inflammation processes rather than to the pro-oxidant activity of caeruloplasmin.

Background: Elevated homocysteine level increases vascular disease risk. Most data are based on subjects younger than 60 years; data for the elderly are more limited. We examined the relationship of homocysteine level to incident myocardial infarction and stroke among older subjects in a nested case-control study., Methods: Subjects were participants in the Rotterdam Study, a cohort study among 7983 subjects residing in the Ommoord district of Rotterdam, the Netherlands. Baseline examinations were performed from March 1, 1990, to July 31, 1993. The analysis is restricted to myocardial infarction and stroke that occurred before December 31, 1994. One hundred four patients with a myocardial infarction and 120 with a stroke were identified with complete data. Control subjects consisted of a sample of 533 subjects drawn from the study base, free of myocardial infarction and stroke. Nonfasting total homocysteine levels were measured., Results: Results were adjusted for age and sex. The risk of stroke and myocardial infarction increased directly with total homocysteine. The linear coefficient suggested a risk increase by 6% to 7% for every 1-micromol/L increase in total homocysteine. The risk by quintiles of total homocysteine level was significantly increased only in the group with levels above 18.6 micromol/L (upper quintile): odds ratios were 2.43 (95% confidence interval, 1.11-5.35) for myocardial infarction and 2.53 (95% confidence interval, 1.19-5.35) for stroke. Associations were more pronounced among those with hypertension., Conclusions: The present study, based on a relatively short follow-up period, provides evidence that among elderly subjects an elevated homocysteine level is associated with an increased risk of cardiovascular disease.

The vitamin B6 status of 84 patients with acute myocardial infarction was compared with that of 84 control subjects. Pyridoxal and pyridoxal 5'-phosphate (PLP) in plasma and erythrocytes, as well as the basal and total potential activity of the PLP-dependent enzyme aspartate aminotransferase in erythrocytes, were measured for a comprehensive assessment of vitamin B6 status. The mean levels of all vitamin B6 indexes (except pyridoxal) were lower in the patients than in the control subjects. The differences were statistically significant, except for erythrocyte PLP and total potential enzyme activity. The adjusted relative odds of a myocardial infarction for subjects in the lowest quartile of plasma PLP was about 5 times higher when compared with those in the highest quartile (relative odds = 5.2, 95% confidence interval = 1.4 to 18.9). Similar findings were found with the other vitamin B6 indexes. No significant association between infarct size, as estimated by creatine kinase level, and the vitamin B6 indexes was observed.

To study the association between selenium status and the risk of myocardial infarction, we compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls (31.3 +/- 8.4 U/g of hemoglobin and 28.0 +/- 8.1 U/g of hemoglobin, respectively). Because the toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event.

This study investigates whether the interaction between angiotensin-converting enzyme (ACE) inhibitors or β-blockers and the ACE insertion/deletion (I/D) polymorphism or angiotensin receptor II type 1 (AGTR1) 573C/T polymorphism modifies the risk of myocardial infarction (MI) or stroke. In total, 4097 subjects with hypertension were included in this study. The drug–gene interaction on the risk of MI or stroke was determined with a Cox proportional hazard model. The risk of MI was reduced in current users of ACE inhibitors with the AGTR1 573CT or CC genotype compared to ACE inhibitors with the AGTR1 573TT genotype (synergy index (SI):0.32; 95% confidence interval (CI): 0.14–0.70). No significant drug–gene interaction was found on the risk of stroke (SI:0.82; 95% CI: 0.44–1.52) or in β-blocker users. Also, no significant drug–gene interaction was found with the ACE I/D polymorphism. In conclusion, subjects with at least one copy of the AGTR1 573C allele might have more benefit from ACE inhibitor therapy.The Pharmacogenomics Journal (2008) 8, 400–407; doi:10.1038/sj.tpj.6500493; published online 18 March 2008 [ABSTRACT FROM AUTHOR]

The aim was to examine the risk profiles and prognosis of treated and untreated hypertensive subjects and examine to what degree confounding by indication was present in a population-based cohort study with up to 30-year follow-up. The study population consisted of 9328 men and 10?062 women, aged 33-87 years at the time of attendance from 1967 to 1996. The main outcome measures were myocardial infarction (MI), cardiovascular disease (CVD) mortality and all-cause mortality. Comparing the risk profiles between treated and untreated subjects entering the study showed significantly higher values for some risk factors for treated subjects. During the first 10 years, hypertensive men without treatment, compared with those treated, had a significantly lower risk of suffering MI, CVD and all-cause mortality, hazard ratio (HR) 0.72 (95% CI; 0.57, 0.90), 0.75 (95% CI; 0.59, 0.95) and 0.81 (95% CI; 0.61, 0.98), respectively. No significant differences in outcome were seen during the following 20 years. In identically defined groups of women, no significant differences in mortality were seen between groups. Subgroup analysis, at two stages of the study 5 years apart, revealed that some cardiovascular risk factors had a higher prevalence in hypertensive men who were treated at the later stage, compared with those who remained untreated (P=0.004). In conclusion, hypertensive treated men had a worse prognosis during the first 10 years of follow-up than untreated ones, which is most likely due to worse baseline risk profile. Hypertensive men that were treated at a later stage had a worse risk profile than those not treated at a later stage.Journal of Human Hypertension (2004) 18, 615-622. doi:10.1038/sj.jhh.1001725 Published online 8 April 2004 [ABSTRACT FROM AUTHOR]