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Abstract. Moerman CJ, van Hout BA, Bonneux L, Witteman JCM (University of Amsterdam, Amsterdam, and Erasmus University Medical School, Rotterdam, the Netherlands). Postmenopausal hormone therapy: less favourable risk–benefit ratios in healthy Dutch women. J Intern Med 2000; 248: 143–150. 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. [ABSTRACT FROM AUTHOR]

Objectives: Changes in cardiovascular risk factors with menopausal status are difficult to study, owing to the high correlation of menopausal status with age. Therefore we examined cardiovascular risk factors in a meticulously selected population in which the contrast in oestrogen status between pre- and postmenopausal women of the same age was maximized.Design: Risk factors were compared in 93 premenopausal and 93 postmenopausal women who were matched on age (range 43-55 years).Setting: The women were selected from respondents to a mailed questionnaire about the menopause, which was sent to all women aged 40-60 years in the Dutch town of Zoetermeer (n = 12 675; response 54%).Subjects: Postmenopausal women who were at least 3 years after menopause or whose menses had stopped naturally before age 48 were age-matched with premenopausal women with regular menses and without menopausal complaints.Results: Compared to premenopausal women, postmenopausal women had significantly increased levels of total cholesterol (10.0%, 95% confidence interval 5.1-14.0), low density lipoprotein (LDL) cholesterol (14.0%, 6.9-19.9), and apolipoprotein B (8.2%, 0.6-15.5). The difference was present within 3 years after onset of menopause and did not show a trend towards an increase with the number of postmenopausal years. No differences were found in high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1, blood glucose, insulin, body mass index, waist-to-hip ratio, and systolic and diastolic blood pressure.Conclusions: The results of this study add to the evidence that total cholesterol, LDL cholesterol and apolipoprotein B are the primary cardiovascular risk factors affected by menopause. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To relate cross-sectionally assessed indicators of carotid atherosclerosis measured in participants of the Rotterdam Study to absolute 10-12 year risks of stroke, coronary heart disease and death estimated by risk functions available from other studies.Setting: General population living in the suburb of Ommoord in Rotterdam, The Netherlands.Subjects: A sample of men and women (n = 1683), aged 55 years or over, drawn from participants from the Rotterdam Study (n = 7983).Main Outcomes Measures: Three risk scores were used to estimate for each individual the absolute risk of stroke, coronary heart disease and death within 10-12 years as a function of their cardiovascular risk factor profile. Cross-sectionally measured indicators of carotid atherosclerosis (presence of atherosclerotic lesions and common carotid intima-media thickness) were subsequently related to these risk scores.Results: The 10-year absolute risk of stroke increased linearly from 4.8% (95% CI = 3.8, 5.8) for subjects in the lowest quintile to 16.1% (12.3, 21.9) for subjects in the highest quintile of common carotid intima-media thickness distribution. Similarly, the 10-year absolute risk for coronary heart disease rose from 13.1% (95% CI = 12.0, 14.2) to 23.4% (95% CI = 21.4, 25.4), whereas the risk of death within 11.5 years rose from 15.0% (95% CI = 12.8, 17.4) in the lowest quintile to 46.0% (42.8, 49.3) in the upper quintile. The absolute risks of stroke, coronary heart disease or death rose from 8.8, 15.8 and 26.9% to 14.3, 19.8 and 40.9%, respectively, when plaques in the common carotid artery were present. Similar findings were observed for plaques in the carotid bifurcation.Conclusion: Common carotid intima-media thickness and carotid plaques are markers for increased risk of stroke, coronary heart disease and death within 10-12 years. [ABSTRACT FROM AUTHOR]

Aims Modulation of dopamine receptor D2 ( DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. Methods Four potentially functional variants in the coding region of the DRD2/ ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for Type 2 diabetes susceptibility in up to 25 000 people (8148 with Type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. Results rs1800497 at the DRD2/ ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*10−4) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women ( P = 5.5*10−4) but again not in men ( P = 0.34). Conclusion The present data identify DRD2/ ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene. [ABSTRACT FROM AUTHOR]

Objective We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes. Design Population-based birth cohort study. Setting Data of pregnant women and their children in Rotterdam, the Netherlands. Population In 8541 mothers, height, prepregnancy body mass index (BMI) and gestational weight gain were available. Methods Fetal growth was measured by ultrasound in mid- and late pregnancy. Regression analyses were used to assess the impact of maternal anthropometrics on fetal weight and birth outcomes. Main outcome measures Fetal weight and birth outcomes: weight (grams) and the risks of small (<5th percentile) and large (>95th percentile) size for gestational age at birth. Results Maternal BMI in pregnancy was positively associated with estimated fetal weight during pregnancy. The effect estimates increased with advancing gestational age. All maternal anthropometrics were positively associated with fetal size ( P-values for trend <0.01). Mothers with both their prepregnancy BMI and gestational weight gain quartile in the lowest and highest quartiles showed the highest risks of having a small and large size for gestational age child at birth, respectively. The effect of prepregnancy BMI was strongly modified by gestational weight gain. Conclusions Fetal growth is positively affected by maternal BMI during pregnancy. Maternal height, prepregnancy BMI and gestational weight gain are all associated with increased risks of small and large size for gestational age at birth in the offspring, with an increased effect when combined. [ABSTRACT FROM AUTHOR]

Several β-blockers are metabolized by the polymorphic enzyme cytochrome P450 2D6 (CYP2D6). CYP2D6*4 is the main polymorphism leading to decreased enzyme activity. The clinical significance of impaired elimination of β-blockers is controversial, and most studies suffer from inclusion of small numbers of poor metabolizers (PMs) of CYP2D6. In this study, the association between CYP2D6*4 and blood pressure or heart rate was examined in 1,533 users of β-blockers in the Rotterdam Study, a population-based cohort study. In CYP2D6 *4/*4 PMs, the adjusted heart rate in metoprolol users was 8.5 beats/min lower compared with *1/*1 extensive metabolizers (EMs) (P < 0.001), leading to an increased risk of bradycardia in PMs (odds ratio = 3.86; 95% confidence interval 1.68–8.86; P = 0.0014). The diastolic blood pressure in PMs was 5.4 mm Hg lower in users of β-blockers metabolized by CYP2D6 (P = 0.017) and 4.8 mm Hg lower in metoprolol users (P = 0.045) compared with EMs. PMs are at increased risk of bradycardia.Clinical Pharmacology & Therapeutics (2008); 85, 1, 45–50 doi:10.1038/clpt.2008.172 [ABSTRACT FROM AUTHOR]

Objective: The ‘vascular depression’ hypothesis suggests that late-life depression results from vascular brain damage. We studied the longitudinal association between cerebrovascular risk factors and incident depression in a large population-based study. Method: Two thousand nine hundred and thirty-one persons with the age of ≥61 years were followed up. Data on a comprehensive set of cerebrovascular risk factors were collected at baseline. Participants received a psychiatric assessment 5 years later to establish DSM-IV diagnoses. Results: Only current smoking and antihypertensive drug use were independently associated with incident depressive symptoms. Diabetes mellitus and the Framingham stroke risk score were related to incident depressive disorder. No relation with depression was observed for cholesterol, diastolic and systolic blood pressure, history of cardiovascular disease, atrial fibrillation, left ventricular hypertrophy or the use of statins and anticoagulants. Conclusion: These results moderately support the ‘vascular depression’ hypothesis. [ABSTRACT FROM AUTHOR]

The article develops charts for ultrasound dating of pregnancy based on crown-rump length and biparietal diameter. It also derives reference curves for normal fetal growth based on biparietal diameter, head circumference, transverse cerebellar diameter, abdominal circumference and femur length from ten weeks of gestational age onwards.

Objective To examine whether differences in birthweight of various ethnic groups residing in the Netherlands can be explained by determinants of birthweight. Design Population-based birth cohort study. Setting Data of pregnant women and their partners in Rotterdam, the Netherlands. Population We examined data of 6044 pregnant women with a Dutch, Moroccan, Turkish, Capeverdean, Antillean, Surinamese-Creole, Surinamese-Hindustani and Surinamese-other ethnic background. Methods Regression analyses were used to assess the impact of biomedical, socio-demographic and lifestyle-related determinants on birthweight differences. Main outcome measure Birthweight was established immediately after delivery in grams. Results Compared with mean birthweight of offspring of Dutch women (3485 g, SD 555), the mean birthweight was lower in all non-Dutch populations, except in Moroccans. Differences ranged from an 88-g lower birthweight in offspring of the Turkish women to a 424-g lower birthweight in offspring of Surinamese-Hindustani women. Differences in gestational age, maternal and paternal height largely explained the lower birthweight in the Turkish, Antillean, Surinamese-Creole and Surinamese-other populations. Differences in birthweight between the Dutch and the Capeverdean and Surinamese-Hindustani populations could only partly be explained by the studied determinants. Conclusions These results confirm significant differences in birthweight between ethnic populations that can only partly be understood from established determinants of birthweight. The part that is understood points to the importance of determinants that cannot easily be modified, such as parental height. Further study is necessary to obtain a fuller understanding. [ABSTRACT FROM AUTHOR]

What is already known about this subject • To our knowledge, there are no prior studies which investigate whether there is a drug–gene interaction between the three genes involved in the renin–angiotensin system and ACE-inhibitor therapy or β-blocker therapy with these subclinical measurements of atherosclerosis. • Some studies have found an effect on blood pressure or stroke/myocardial infarction, although the results are not conclusive. What this study adds • The results do not indicate the presence of a strong drug–gene interaction between the use of ACE-inhibitors or β-blockers and the ACE insertion/deletion, AGT M235T or AGTR1573C/T polymorphism on the overall risk of atherosclerosis. Aims To investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen M235T or angiotensin II receptor type 1 573C/T polymorphism modify the risk of atherosclerosis associated with β-blocker or ACE-inhibitor therapy. Methods Data were used from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, which started in 1990 and included 7983 subjects of ≥ 55 years. In this study, 2216 subjects with hypertension were included. Three subclinical measurements were used for atherosclerosis, i.e. peripheral arterial disease, carotid atherosclerosis and aortic atherosclerosis. The interaction between antihypertensive drugs and genetic polymorphisms on the risk of atherosclerosis was determined with binary logistic regression analysis. Results The risk of aortic atherosclerosis associated with long-term (≥4 years) β-blocker treatment compared with no use of β-blockers was higher in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene [synergy index (SI) = 3.36; 95% confidence interval (CI) 1.14, 9.97]. The risk of carotid atherosclerosis associated with long-term ACE-inhibitor treatment compared with no use of ACE-inhibitors was lower in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene (SI = 0.20; 95% CI 0.04, 0.95). Conclusion Overall, the risk of atherosclerosis in hypertensives taking a β-blocker or ACE-inhibitor-based regimen was not strongly modified by any of the three candidate gene polymorphisms. [ABSTRACT FROM AUTHOR]

Objectives The objectives of this study were to determine ethnic differences in prenatal growth and to examine their association with differences in maternal and fetal characteristics such as maternal height, weight, age, parity and fetal gender. Methods A total of 1494 women from Rotterdam, The Netherlands, with a low-risk pregnancy who participated in a population-based cohort study, the Generation R Study, were offered three ultrasound examinations during pregnancy. Multilevel modeling was applied to determine ethnic differences in (estimated) fetal weight (including birth weight) and in the separate biometric variables that were used to calculate the estimated fetal weight (abdominal circumference, head circumference and femur length). Additionally the association of ethnic differences with maternal and fetal characteristics (i.e. maternal weight, height, age, parity and fetal gender) was studied. Results Turkish, Cape Verdian, Surinamese-Creole and Surinamese-Hindustani women had on average smaller fetuses than the native Dutch women. The differences became more pronounced towards term. In the Turkish group the differences were no longer statistically significant when adjusted for maternal weight, height, age, parity and fetal gender. In the Cape Verdian, Surinamese-Creole and Surinamese-Hindustani groups the differences decreased after adjustment (31%, 16% and 39%, respectively). Conclusions This study shows that there are ethnic differences in fetal growth, which to a large extent may be attributed to differences in maternal weight, height, age and parity. For some ethnic groups, however, additional factors are involved, as differences remain significant after correction for fetal and maternal characteristics. [ABSTRACT FROM AUTHOR]

The genetic and environmental risk factors, which may influence longevity and mortality, have received much attention during more than one decade. One of the major risks for mortality is cardiovascular disease and the renin angiotensin system (RAS) plays a major role in maintaining blood pressure homeostasis. In this system, the Angiotensin Converting Enzyme (ACE) is one of the key regulators and has been studied in relation to cardiovascular disease and mortality. We aimed to evaluate if the ACE I/D polymorphism is related to total mortality in the elderly. Some 6968 elderly individuals from the Rotterdam study were genotyped for this polymorphism. Smoking was studied as a possible covariable or effect modifier. To examine the effect of the ACE genotype on mortality, a Cox proportional hazards model was fitted. Our results show an increased risk of total mortality in subjects with age at death below 65 years carriers of the DD genotype (HR 1·8, 95% CI 1·1–2·9, P = 0·016). This association was significant in total and cause specific mortality only in those who smoke ( P-value < 0·001 for gene–age interaction). Our findings suggest that the ACE gene is rather associated with early mortality than with late. Individuals who carry the DD genotype appear to be susceptible to early mortality if they smoke, suggesting a possible interaction between smoking and the ACE gene. Eur J Clin Invest 2005; 35 (7): 444 –449 [ABSTRACT FROM AUTHOR]

SummaryObjective: Description and application of an adapted semiquantitative food frequency questionnaire (SFFQ) for dietary assessment in the elderly population of the Rotterdam Study. Design: Dietary assessment consisting of a two-step approach was performed in 5434 participants (2225 men, 3029 women) of the Rotterdam Study from 1990 to 1993, a population-based prospective cohort of 7983 subjects aged 55–95 years (participation rate 78%). Statistical analysis: Nutrient intake was calculated for men and women in four age groups (55–64 years, 65–74 years, 75–84 years, 85–95 years) and linear trend analysis for differences in mean nutrient intake across age groups (55–64 years, 65–74 years, 75–95 years) by regression analysis was conducted. The influence of baseline characteristics on energy and nutrient intakes adjusted by age and sex was investigated by one-way-analysis of variance. Results: The adapted SFFQ made it possible to measure nutrient intake in the elderly within a limited time frame (2×20 min) across a wide age range (55–95 years). For nutrient intake we observed a general decline in mean intake of energy and most nutrients with age in men. In women the relation with age was not consistent: for most nutrients mean intake showed a decrease with age (e.g. water, magnesium, potassium), for some an increase (e.g. total fat, saturated fat, mono/disaccharides), and some nutrients showed no substantial change (e.g. calcium, retinol). Reported nutrient intake was influenced by body mass index, smoking status, socioeconomic status and activities of daily living. A prescribed diet was reported by 12.9% of participants and 34.6% used supplements on a regular basis. Conclusions: The described two-step approach for dietary assessment in the elderly facilitated collection of data on dietary habits across a wide age range and within a limited time frame making it a suitable instrument for... [ABSTRACT FROM AUTHOR]

We investigated whether the insertion/deletion (I/D) polymorphism of theACEgene modified the adherence to ACE inhibitors as measured by the discontinuation of an ACE inhibitor, or addition of another antihypertensive drug.This was a cohort study among 239 subjects who started ACE inhibitor therapy. A Cox proportional hazard model was used to calculate relative risk (RR).During follow-up there was no significant difference between subjects with the DD, ID or II genotype (DDvsII; RR = 1.17, 95%CI: 0.78, 1.77 and IDvsII; RR = 1.06, 95%CI: 0.73, 1.55) in adherence.The I/D polymorphism of theACEgene does not influence the adherence to ACE inhibitors. [ABSTRACT FROM AUTHOR]

Drugs of abuse stimulate striatal dopamine release and activate reward pathways. This study examined the impact of alcohol and cannabis marketing on the reward circuit in alcohol and cannabis users while sober and intoxicated. It was predicted that alcohol and cannabis marketing would increase striatal activation when sober and that reward sensitivity would be less during alcohol and cannabis intoxication. Heavy alcohol (n = 20) and regular cannabis users (n = 21) participated in a mixed factorial study involving administration of alcohol and placebo in the alcohol group and cannabis and placebo in the cannabis group. Non-drug users (n = 20) served as between group reference. Brain activation after exposure to alcohol and cannabis marketing movies was measured using functional magnetic resonance imaging and compared between groups while sober and compared with placebo while intoxicated. Implicit alcohol and cannabis cognitions were assessed by means of a single-category implicit association test. Alcohol and cannabis marketing significantly increased striatal BOLD activation across all groups while sober. Striatal activation however decreased during intoxication with alcohol and cannabis. Implicit associations with cannabis marketing cues were significantly more positive in alcohol and cannabis users as compared with non-drug using controls. Public advertising of alcohol or cannabis use elicits striatal activation in the brain's reward circuit. Reduction of marketing would reduce brain exposure to reward cues that motivate substance use. Conversely, elevated dopamine levels protect against the reinforcing potential of marketing., (© 2016 Society for the Study of Addiction.)

Objective: We aimed to examine the associations of maternal anthropometrics with fetal weight measured in different periods of pregnancy and with birth outcomes., Design: Population-based birth cohort study., Setting: Data of pregnant women and their children in Rotterdam, the Netherlands., Population: In 8541 mothers, height, prepregnancy body mass index (BMI) and gestational weight gain were available., Methods: Fetal growth was measured by ultrasound in mid- and late pregnancy. Regression analyses were used to assess the impact of maternal anthropometrics on fetal weight and birth outcomes., Main Outcome Measures: Fetal weight and birth outcomes: weight (grams) and the risks of small (<5th percentile) and large (>95th percentile) size for gestational age at birth., Results: Maternal BMI in pregnancy was positively associated with estimated fetal weight during pregnancy. The effect estimates increased with advancing gestational age. All maternal anthropometrics were positively associated with fetal size (P-values for trend <0.01). Mothers with both their prepregnancy BMI and gestational weight gain quartile in the lowest and highest quartiles showed the highest risks of having a small and large size for gestational age child at birth, respectively. The effect of prepregnancy BMI was strongly modified by gestational weight gain., Conclusions: Fetal growth is positively affected by maternal BMI during pregnancy. Maternal height, prepregnancy BMI and gestational weight gain are all associated with increased risks of small and large size for gestational age at birth in the offspring, with an increased effect when combined.

Objective: To examine whether differences in birthweight of various ethnic groups residing in The Netherlands can be explained by determinants of birthweight., Design: Population-based birth cohort study., Setting: Data of pregnant women and their partners in Rotterdam, The Netherlands., Population: We examined data of 6044 pregnant women with a Dutch, Moroccan, Turkish, Capeverdean, Antillean, Surinamese-Creole, Surinamese-Hindustani and Surinamese-other ethnic background., Methods: Regression analyses were used to assess the impact of biomedical, socio-demographic and lifestyle-related determinants on birthweight differences., Main Outcome Measure: Birthweight was established immediately after delivery in grams., Results: Compared with mean birthweight of offspring of Dutch women (3485 g, SD 555), the mean birthweight was lower in all non-Dutch populations, except in Moroccans. Differences ranged from an 88-g lower birthweight in offspring of the Turkish women to a 424-g lower birthweight in offspring of Surinamese-Hindustani women. Differences in gestational age, maternal and paternal height largely explained the lower birthweight in the Turkish, Antillean, Surinamese-Creole and Surinamese-other populations. Differences in birthweight between the Dutch and the Capeverdean and Surinamese-Hindustani populations could only partly be explained by the studied determinants., Conclusions: These results confirm significant differences in birthweight between ethnic populations that can only partly be understood from established determinants of birthweight. The part that is understood points to the importance of determinants that cannot easily be modified, such as parental height. Further study is necessary to obtain a fuller understanding.

Aims: To investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen M235T or angiotensin II receptor type 1 573C/T polymorphism modify the risk of atherosclerosis associated with beta-blocker or ACE-inhibitor therapy., Methods: Data were used from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, which started in 1990 and included 7983 subjects of >or= 55 years. In this study, 2216 subjects with hypertension were included. Three subclinical measurements were used for atherosclerosis, i.e. peripheral arterial disease, carotid atherosclerosis and aortic atherosclerosis. The interaction between antihypertensive drugs and genetic polymorphisms on the risk of atherosclerosis was determined with binary logistic regression analysis., Results: The risk of aortic atherosclerosis associated with long-term (>or=4 years) beta-blocker treatment compared with no use of beta-blockers was higher in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene [synergy index (SI) = 3.36; 95% confidence interval (CI) 1.14, 9.97]. The risk of carotid atherosclerosis associated with long-term ACE-inhibitor treatment compared with no use of ACE-inhibitors was lower in subjects with the TT genotype than in subjects with the MM genotype of the AGT gene (SI = 0.20; 95% CI 0.04, 0.95)., Conclusion: Overall, the risk of atherosclerosis in hypertensives taking a beta-blocker or ACE-inhibitor-based regimen was not strongly modified by any of the three candidate gene polymorphisms.

Aims: We investigated whether the insertion/deletion (I/D) polymorphism of the ACE gene modified the adherence to ACE inhibitors as measured by the discontinuation of an ACE inhibitor, or addition of another antihypertensive drug., Methods: This was a cohort study among 239 subjects who started ACE inhibitor therapy. A Cox proportional hazard model was used to calculate relative risk (RR)., Results: During follow-up there was no significant difference between subjects with the DD, ID or II genotype (DD vs II; RR = 1.17, 95%CI: 0.78, 1.77 and ID vs II; RR = 1.06, 95%CI: 0.73, 1.55) in adherence., Conclusions: The I/D polymorphism of the ACE gene does not influence the adherence to ACE inhibitors.