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Biomedical subjects

Olaf H Klungel

Publications and source records attributed to Olaf H Klungel.

At least 19 recordsLinked to original sources
PubMed2007

Absence of an interaction between the angiotensin-converting enzyme insertion-deletion polymorphism and pravastatin on cardiovascular disease in high-risk hypertensive patients: the Genetics of Hypertension-Associated Treatment (GenHAT) study.

BACKGROUND: The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) insertion-deletion (ID) polymorphism interacts with pravastatin to modify the risk of coronary heart disease (CHD) and other cardiovascular end points in a large clinical trial. METHODS: GenHAT is an ancillary study of the ALLHAT. The ACE ID genotyped population in the lipid-lowering arm of ALLHAT included 9467 participants randomly assigned to pravastatin (n = 4741) or to usual care (n = 4726). The efficacy of pravastatin in reducing the risk of primary outcome (all-cause mortality) and secondary outcomes (fatal CHD and nonfatal myocardial infarction, cardiovascular disease [CVD] mortality, CHD, stroke, other CVD, non-CVD mortality, stroke, and heart failure) was compared between the genotype strata (dominant model ID + II vs DD, additive model II vs ID vs DD), by examining an interaction term in a Cox proportional hazards model. RESULTS: The relative risk of fatal CHD and nonfatal myocardial infarction among subjects randomized to pravastatin compared with subjects randomized to usual care was similar in subjects with the II genotype (hazard ratio [HR] 0.84, 95% CI 0.59-1.18), the ID genotype (HR 0.84, 95% CI 0.68-1.03), and the DD genotype (HR 0.99, 95% CI 0.77-1.27). CONCLUSIONS: We found no evidence that the ACE ID genotype was a major modifier of the efficacy of pravastatin in reducing the risk of cardiovascular events.

Aged↗
PubMed2006

Adherence to evidence-based statin guidelines reduces the risk of hospitalizations for acute myocardial infarction by 40%: a cohort study.

AIMS: To investigate the 'real world' effectiveness of robust statin therapy, focusing on the effect of dose and early treatment discontinuation on the risk of hospitalization for acute myocardial infarction (AMI). METHODS AND RESULTS: In the PHARMO database, including among others drug-dispensing and hospital discharge records for more than two million subjects in the Netherlands, 59,094 new users of statins in the period 1 January 1991 until 31 December 2004, >or=18 years of age were identified. In these patients, exposure to statins, both in terms of persistence and dose, was determined over the first two treatment years. To determine the risk for AMI, patients were followed from this 2-year time point until the first hospital admission for AMI, death, or end of the study period. A total of 31,557 patients (53%) discontinued statin use within 2 years; 20 883 patients (35%) were persistent users with an average equipotent dose>or=4. A 30% reduction in risk of hospitalization for AMI with persistent statin use was observed. The protective effect increased with a higher dose (20 and 40% risk reduction with an equipotent dose or=4, respectively). CONCLUSION: These results show that statins are suboptimally used in real life for having the maximum benefit in terms of preventing AMI.

Adult↗
PubMed2006

The influence of the alpha-adducin G460W polymorphism and angiotensinogen M235T polymorphism on antihypertensive medication and blood pressure.

Despite the availability of a variety of effective antihypertensive drugs, inadequate control of blood pressure is common in hypertensive patients. The aim of this study was investigate whether the alpha-adducin G460W polymorphism or angiotensinogen M235T polymorphism has an effect on the mean difference in blood pressure in subjects using antihypertensive drugs. Data from the Rotterdam Study, a population-based prospective cohort study in the Netherlands, was used. This study started in 1990 and included 7983 subjects of 55 years and older. Data from three examination rounds were used. Subjects were included when their blood pressure was elevated at 1 or more examinations and/or a diuretic, beta-blocker, calcium antagonist, or ACE inhibitor was used. A marginal generalized linear model was used to assess the drug-gene interaction. In total, 3025 hypertensives were included. No drug-gene interaction on blood pressure levels was found. The mean difference in systolic blood pressure (SBP) between subjects with the W-allele and GG genotype of the alpha-adducin gene was for diuretic users 1.25 mmHg (95% CI:-2.86 to 5.35), for beta-blockers 0.02 mmHg (95% CI:-3.39 to 3.42), for calcium antagonists -0.70 mmHg (95% CI:-5.61 to 4.21), and for ACE inhibitors -3.50 mmHg (95% CI:-9.02 to 2.02). The mean difference in SBP between subjects with the TT and MM genotype was for diuretic users -2.33 mmHg (95% CI:-8.32 to 3.66), for beta-blocker -0.06 mmHg (95% CI:-4.91 to 4.79), for calcium antagonist 0.59 mmHg (95% CI:-5.95 to 7.13), and for ACE inhibitor -2.33 mmHg (95% CI:-9.66 to 5.01). The G460W polymorphism and the M235T polymorphism did not modify the difference in blood pressure levels among subjects who used diuretics, beta-blockers, calcium antagonists, or ACE inhibitors.

Adrenergic beta-Antagonists↗
PubMed2006

Regional influences on the dispensing of glucose test strips in Dutch community pharmacies.

BACKGROUND: Pharmacy practice guidelines promote the role of community pharmacies in self-monitoring of blood glucose. However, variations between Dutch pharmacies exist in the proportion of patients to whom test strips are dispensed. OBJECTIVE: To assess whether variations between community pharmacies in dispensing of blood glucose test strips can be explained by differences in patient characteristics and the region in which the pharmacy is located. SETTING: PHARMO-Record Linkage System containing drug dispensing histories from 40 community pharmacies of about 450,000 patients in the Netherlands. METHOD: We performed a retrospective cohort study. Data on prescription of all drugs and medical aids between 1991 and 2001 were extracted for all new users of antidiabetic drugs. Patients were excluded if the dispensing history did not allow classification of the type of diabetes or if the dispensing pharmacy could not be determined. The data were analysed using a Cox proportional hazard model. MAIN OUTCOME MEASURE: Time to first test strips dispensed. RESULTS: We identified 8,233 starters of antidiabetic drugs. During a median follow-up of 2.1 years, 20% of the patients were dispensed test strips at least once. Community pharmacy was significantly associated with the dispensing of test strips after adjustment for patient characteristics. This association was less apparent when stratified for the geographical location of the pharmacy. CONCLUSION: Community pharmacy is an independent determinant of the start of use of test strips. Differences in dispensing of test strips between pharmacies are dependent on geographical region. This suggests that implementing practice guidelines for diabetes care in community pharmacy requires different approaches in different regions.

Adult↗
PubMed2006

Drug-gene interaction between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and antihypertensive therapy.

BACKGROUND: Despite the availability of a variety of effective drugs, inadequate control of blood pressure is common. There are some indications that the angiotensin-converting enzyme (ACE) gene modifies the response to antihypertensive drugs, but the results have been inconclusive. OBJECTIVE: To investigate whether the insertion/deletion polymorphism of the ACE gene modifies blood pressure differences among subjects using diuretics, beta-blockers, calcium-channel antagonists, or ACE inhibitors. 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 aged 55 years or older. Data from 3 subsequent cross-sectional investigations were used, as well. Subjects were included if they had high blood pressure during one or more examinations and/or used monotherapy with a diuretic, beta-blocker, calcium-channel antagonist, or ACE inhibitor. A marginal, generalized, linear model was used to assess the association between the mean difference in systolic/diastolic blood pressure and antihypertensive classes stratified by the 3 genotypes. RESULTS: In total, 3025 hypertensive individuals were included, and 6500 measurements of blood pressure were taken. The percentages of DD, ID, and II genotypes were 28.3%, 51.4%, and 20.3%, respectively. The mean differences in systolic blood pressure between the II and DD genotypes were 0.23 mm Hg (95% CI -5.48 to 5.94) for diuretics, -2.41 mm Hg (95% CI -6.72 to 1.90) for beta-blockers, 2.12 mm Hg (95% CI -4.64 to 8.89) for calcium-channel antagonists, and -2.01 mm Hg (95% CI -9.82 to 5.79) for ACE inhibitors. CONCLUSIONS: The adjusted mean difference in diastolic and systolic blood pressure among diuretic, beta-blocker, calcium-channel antagonist, or ACE inhibitor users was not modified by the ACE insertion/deletion polymorphism.

Aged↗
PubMed2006

Initial non-compliance with antihypertensive monotherapy is followed by complete discontinuation of antihypertensive therapy.

PURPOSE: Discontinuation with treatment is a major problem in the treatment of hypertension. The objective of our study was to assess the association between non-compliance and discontinuation in patients who started using antihypertensive monotherapy. METHODS: A nested case-control study within a cohort of new users of antihypertensive drugs between 1st January 1999 and 31st December 2002 was performed. We used data from the PHARMO database, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 subjects. Cases discontinued their use of antihypertensive monotherapy and were not switched to other antihypertensive treatment, controls stayed on their initially prescribed monotherapy. Conditional logistic regression was used to calculate odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: In a cohort of 39,714 new users of antihypertensive drugs, we identified 9111 cases and 9111 matched controls. The percentage of non-compliant patients (compliance < 80%) among cases and controls was 14.0% and 5.8%, respectively [OR 2.86 (95%CI: 2.52-3.24)]. Patients who used less than 90 days had a higher risk on discontinuation [OR 3.10 (95%CI: 2.67-3.59)] than patients who used more than 90 days [OR 2.28 (95%CI: 1.79-2.92)]. The association was generally similar among males and females, among the different types of antihypertensives and among the different age groups. CONCLUSION: In patients who start antihypertensive monotherapy, non-compliance is often followed by discontinuation of this antihypertensive treatment. The pharmacy medication history is a valuable tool for physicians to identify patients who have a high risk on discontinuation with antihypertensive treatment.

Adolescent↗
PubMed2006

Instrumental variables: application and limitations.

To correct for confounding, the method of instrumental variables (IV) has been proposed. Its use in medical literature is still rather limited because of unfamiliarity or inapplicability. By introducing the method in a nontechnical way, we show that IV in a linear model is quite easy to understand and easy to apply once an appropriate instrumental variable has been identified. We also point out some limitations of the IV estimator when the instrumental variable is only weakly correlated with the exposure. The IV estimator will be imprecise (large standard error), biased when sample size is small, and biased in large samples when one of the assumptions is only slightly violated. For these reasons, it is advised to use an IV that is strongly correlated with exposure. However, we further show that under the assumptions required for the validity of the method, this correlation between IV and exposure is limited. Its maximum is low when confounding is strong, such as in case of confounding by indication. Finally, we show that in a study in which strong confounding is to be expected and an IV has been used that is moderately or strongly related to exposure, it is likely that the assumptions of IV are violated, resulting in a biased effect estimate. We conclude that instrumental variables can be useful in case of moderate confounding but are less useful when strong confounding exists, because strong instruments cannot be found and assumptions will be easily violated.

Bias↗
PubMed2006

Prescribing behaviour according to Dutch and European guidelines on the management of hypercholesterolaemia (1992-1999).

BACKGROUND: The success of the full implementation of a new guideline may depend on the observed discrepancy between daily medical practice developed before the release of the guideline and new treatment recommendations issued by the guideline. AIM: To assess whether the initiation of statin treatment for primary prevention of cardiovascular disease in an elderly population was in agreement with guidelines. METHODS: Data were obtained from the Rotterdam Study, a prospective population-based cohort study consisting of 7983 subjects aged>or=55 years. In the period 1992-1999, all patients starting statins for primary prevention were selected. Treatment eligibility was established according to Dutch guidelines based on considerations of cost effectiveness (1998) and European guidelines based on clinical effectiveness (1998 and 2003). RESULTS: Only 5.7% [95% confidence interval (CI) 3.1, 8.3] of the 299 subjects starting statins for primary prevention met the eligibility criteria of the Dutch guidelines. Most patients (92.0%, 95% CI 88.9, 95.1) met the criteria of the 2003 European guidelines. Patients who did not meet any eligibility criteria were female and had one or less cardiovascular risk factor, except for two patients with total cholesterol levels<5 mmol l-1 prior to start of statin therapy. CONCLUSIONS: The use of statins was in agreement with the most recent European guidelines in over 90% of elderly patients who started statins for primary prevention, but in only 6% of these patients according to the Dutch guidelines. As long as existing guidelines are as discrepant as they are now, variation in agreement between physicians' prescribing and guideline recommendations is unavoidable.

Adult↗
PubMed2006

Drug costs associated with non-adherence to cholesterol management guidelines for primary prevention of cardiovascular disease in an elderly population: the Rotterdam study.

BACKGROUND: In The Netherlands, costs of HMG-CoA reductase inhibitor (statin) use have recently increased sharply compared with costs of other drugs. However, several studies have established both undertreatment and non-guidelines-indicated treatment with statins, suggesting a suboptimal use of resources. OBJECTIVE: To estimate the drug costs associated with non-guidelines-indicated treatment and undertreatment with statins in an elderly population. PATIENTS AND SETTING: Data were obtained from the Rotterdam Study, a population-based prospective cohort study which began in 1990 with 7983 participants aged > or =55 years. Subjects with a history of cardiovascular disease (CVD) were excluded. Pharmacy records were used to assess patterns of medication use in daily medical practice. MAIN OUTCOME MEASURE: Non-guidelines-indicated treatment and undertreatment with statins were established in relation to Dutch cholesterol management guidelines for all participants. We calculated the costs of statin therapy associated with non-guidelines-indicated treatment, and the costs of statins if all those undertreated were to receive statins. The results were projected on to the Dutch population to determine the economic implications of non-adherence to cholesterol management guidelines in the elderly. RESULTS: Of the participants who started treatment with statins for the primary prevention of CVD during follow-up, 69% received non-guidelines-indicated treatment. More men (7.5%) were undertreated than women (1.6%) and more women (6.2%) received non-guidelines-indicated treatment than men (1.5%). Among the participants without CVD who were still alive at 1 January 2002, 14% were eligible for statin therapy but were untreated. After projection of the prevalence of non-guidelines-indicated treatment and undertreatment to the Dutch population, the absolute costs for non-guidelines-indicated treatment with statins in 2005 were estimated to be approximately 23 million euro(uncertainty limits [UL]: 19-28 million euro), while the cost to eliminate undertreatment was also 23 million euro (UL: 19-28 million euro). CONCLUSION: Reallocation of resources used for statin therapy from those receiving non-guidelines-indicated treatment to those being undertreated could lead to a more efficient use of resources.

Aged↗
PubMed2006

A comparison of two multiple-characteristic decision-making models for the comparison of antihypertensive drug classes: Simple Additive Weighting (SAW) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS).

BACKGROUND: Multiple-characteristics decision-making (MCDM) models can be used to calculate a score, based on a set of characteristics, for a number of alternative drugs or drug classes to allow comparison between them and thus enhance evidence-based pharmacotherapy. OBJECTIVE: To compare two MCDM models, Simple Additive Weighting (SAW) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS), in determining first-line antihypertensive drug class. METHODS: Five different classes of antihypertensive drugs were analyzed: diuretics, beta-adrenoceptor antagonists (beta-blockers), dihydropyridine calcium channel blockers (DHP-CCBs), ACE inhibitors, and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). Four characteristics were deemed relevant for the determination of first-line antihypertensive drug class: effectiveness, persistence with treatment as a measure of tolerability, cost, and clinical experience. Weight factors were determined by sending questionnaires to cardiologists, pharmacists, general practitioners (GPs), and internists in The Netherlands. Absolute scores for the characteristics were determined from literature (effectiveness and persistence) and health insurance data (costs and clinical experience). RESULTS: Ninety-two cardiologists (33% of those sent the questionnaire), 90 GPs (31%), 87 internists (31%), and 123 pharmacists (43%) completed the questionnaire. Among all professions, according to both SAW and TOPSIS, ACE inhibitors were ranked as the first-line antihypertensive drug class, typically followed by beta-blockers. CONCLUSION: Both SAW and TOPIS analyses, using weight factors assigned by cardiologists, pharmacists, GPs, and internists from The Netherlands, rank ACE inhibitors as the first choice among antihypertensive drug classes for the treatment of uncomplicated hypertension. Both methods are valuable tools in the development of evidence-based pharmacotherapy.

Adrenergic beta-Antagonists↗
PubMed2005

Generic substitution of antihypertensive drugs: does it affect adherence?

BACKGROUND: Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to therapy. OBJECTIVE: To assess the association between generic substitution and nonadherence to antihypertensive drugs. METHODS: We conducted a matched cohort study between January 1, 1999, and December 31, 2002. Data were obtained from PHARMO, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 people in The Netherlands. Residents of 30 medium-sized cities who initiated antihypertensive drug therapy were potential subjects. Refill adherence with antihypertensive drugs after substitution was determined; those with refill adherence below 80% were considered nonadherent. RESULTS: Four hundred sixty-three patients with a substitution in therapy and 565 controls, matched on age, gender, therapy start date, duration of use, and generic product code, were identified. Of the patients who switched from brand-name to generic formulations ("substituted"), 13.6% were nonadherent, and of the non-substituted patients (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% CI 0.48 to 0.96). The association was absent in males. None of the patients discontinued the medication. No differences in hospitalizations for cardiovascular disease in the 6 months after the substitution were observed. CONCLUSIONS: Generic substitution of antihypertensive drugs does not lead to lower adherence or more discontinuation and cardiovascular disease-related hospitalizations compared with brand-name therapy. When a less-expensive antihypertensive generic equivalent becomes available, generic substitution should be considered to achieve economic benefits.

Adult↗
PubMed2005

Refill persistence with chronic medication assessed from a pharmacy database was influenced by method of calculation.

BACKGROUND AND OBJECTIVES: In literature, different methods of calculating persistence are used. In this study, the effect of using these different methods on persistence and the association of patients characteristics and persistence are assessed. METHODS: The PHARMO record linkage system was used to calculate persistence with antihypertensive drugs for a cohort of 14,466 new users of antihypertensives. Three different types of methods were used to define the maximum gap allowed between two prescriptions that a patient may have to be defined as a continuous user, one based on a defined number of days (varying from 9-365 days), the second based on the duration of the last prescription (varying from 0.1-4 times the duration), the third based on a combination of both methods, whichever leads to the lowest number of days. RESULTS: Refill persistence varied between 19.7-86.4% (method 1), between 27.9-90.2% (method 2), and between 19.7-86.4% (method 3). Furthermore, patient characteristics associated with persistence differed between and within the three different methods. CONCLUSION: The method used and the variation within a method influenced both persistence and the association between patient characteristics and persistence. Results of persistence studies are highly influenced by the researchers' method of the maximum allowed treatment gap.

Adolescent↗
PubMed2005

Collaborative services among community pharmacies for patients with diabetes.

BACKGROUND: Patients performing self-monitoring of blood glucose (SMBG) may benefit from community pharmacy services. However, wide-scale implementation of these services is limited. Many pharmacy characteristics (eg, physical layout of the pharmacy, knowledge and competence of the pharmacy team) are reported to be relevant when implementing these services. Still, the importance of local agreements on the division of roles with, for example, local general practitioners or diabetes nurses, is less clear. OBJECTIVE: To study the association between local collaboration and the level of services provided by community pharmacies to patients performing SMBG. METHODS: In 2004, we performed a cross-sectional survey among all 1692 Dutch community pharmacies. Data were gathered on provision of services for SMBG, local agreements, and pharmacy characteristics. Data were analyzed using logistic regression. Associations were adjusted for pharmacy characteristics. RESULTS: About 44% (724) of the community pharmacies returned the questionnaire. Pharmacies that were not involved in local collaborative services on patient counseling reported to provide fewer services compared with those that were involved in such agreements (OR 0.26, 95% CI 0.13 to 0.53). Similar findings were observed for agreements on calibration of SMBG equipment (0.17, 0.04 to 0.71). The associations remained after adjusting for pharmacy characteristics. CONCLUSIONS: Local collaboration on the division of roles in diabetes care between healthcare professionals is independently associated with the number of pharmacy services provided to patients performing SMBG.

Blood Glucose Self-Monitoring↗
PubMed2005

Effectiveness of interventions by community pharmacists to improve patient adherence to chronic medication: a systematic review.

OBJECTIVE: To systematically review the impact of interventions by community pharmacists on patients' adherence with chronic medication. DATA SOURCES: A MEDLINE search (1966-November 30, 2003) and a review of reference sections were done to identify all pertinent English- and German-language journal articles. Search terms included compliance, adherence, persistence, discontinuation, pharmacist, and intervention. STUDY SELECTION AND DATA EXTRACTION: From each relevant study, the following data were extracted: study design, country, disease, number of patients, patients' age and gender, type of intervention, duration of follow-up, method of measurement of adherence and adherence rate, and data concerning the quality of the included studies. DATA SYNTHESIS: A total of 162 studies were identified, of which 18 matched our inclusion criteria. Twelve were randomized controlled trials and 6 were non-crossover single-group trials. Eight studies showed significant improvement of adherence at one or more time points. Eight studies did not show any effect, 7 of which were randomized controlled trials. In most studies, adherence rates at baseline were high compared with rates reported in the general population. Counseling, monitoring, and education during weekly or monthly appointments showed some effect. However, these same types of interventions showed no effect in other studies. The overall quality of the included studies was low. CONCLUSIONS: Currently, it is impossible to identify an overall successful adherence-improving strategy performed by pharmacists. More well-designed and well-conducted studies on the effectiveness of interventions by a community pharmacist to improve patient adherence to chronic medication need to be performed.

Community Pharmacy Services↗
PubMed2005

Differences in antihypertensive drug persistence associated with drug class and gender: a PHARMO study.

OBJECTIVE: The objective of the study is to investigate factors related to treatment persistence among users of antihypertensive (AHT) drugs in daily practice. METHODS: Data for this study were obtained from the PHARMO database including pharmacy records and hospitalizations in the Netherlands (n=950,000). Patients who newly received AHT therapy (n=17,113) between 1997 and 2001 were selected. Of these patients, random samples of 500 patients per drug class were drawn. One-year persistence was defined as (1) the percentage of patients using AHTs at least 270 days and receiving AHT in 3 months after the 1-year follow-up period, and (2) Catalan method (Kaplan-Meier curves). Gender specific persistence rates per drug class were adjusted for significant factors including age, use of antidiabetics and lipid lowering drugs, and prior cardiovascular hospitalizations (OR and 95%CI). RESULTS: Persistence was highest in users of angiotensin II receptor blockers (ARBs) (62.0%), progressively lower in users of angiotensin converting enzyme inhibitors (ACE-inhibitors, 59.7%), betablockers (35.0%), calcium channel blockers (34.7%), and diuretics (33.0%), resulting in the highest OR of 3.4 [95%CI: 2.6-4.5] for ARBs compared to diuretics. The persistence of AHT use in women was substantially lower (40.1% vs. 50.2%, OR 0.7 [95%CI: 0.6-0.8]) and differences between drug classes were larger than in men. CONCLUSIONS: These results demonstrate marked differences in persistence between AHT classes, with the highest persistence for ARBs and lowest for diuretics. Women were less persistent with their AHT compared to men. This low persistence leads to suboptimal treatment with a potential for substantial clinical consequences. Especially in women, more attention paid to AHT persistence patterns could improve their cardiovascular outcome.

Adult↗
PubMed2005

Cardiovascular drug use and differences in the incidence of cardiovascular mortality in elderly Serbian men.

OBJECTIVE: To assess whether the difference in risk of cardiovascular mortality between urban and rural areas of Serbia could be explained by differences in the use of cardiovascular medication. METHODS: The Serbian cohorts of the Seven Countries Study, Velika Krsna (VK), Zrenjanin (ZR) and Belgrade (BG), were enrolled in 1962-1964 and were followed up for 25 years. The survivors of these cohorts were re-examined in 1987, 1988 and 1989, respectively. This second examination of elderly men aged 65 to 84 years included a questionnaire about current use of cardiovascular medication, risk factors and diseases and a physical examination. All subjects were followed until death or the predefined censor date (10 years after baseline). The Cox proportional hazards model was used to calculate the risk of cardiovascular mortality in the rural cohorts compared to the urban cohort and to adjust for confounding. MAIN OUTCOME MEASURE: Cardiovascular death. RESULTS: A total of 227 men from VK, 184 men from ZR and 287 men from BG were followed for a mean duration of 7.4 years and was complete for all subjects. After exclusion of 13 subjects with missing medication data, the incidences of cardiovascular mortality in VK, ZR, and BG were 60, 74, and 26 per 1,000 person-years, respectively. The prevalence of cardiovascular medication use was 38% in VK, 52% in ZR, and 59% in BG. The greatest difference in use of specific medication was observed for betablockers (0% in VK and ZR, 13% in BG). After adjustment for cardiovascular risk factors, diseases and age, the relative risks (RRs) of cardiovascular mortality were 2.12 [95% CI: 1.44-3.12], and 2.27 [95% CI: 1.56-3.30] in VK, and ZR compared to BG. Additional adjustment for the use of cardiovascular medication increased these RRs to 2.40 [95% CI: 1.61-3.60] and 2.55 [95% CI: 1.72-3.78], respectively. CONCLUSION: The variation in cardiovascular medication use could not explain the excess risk of mortality in the rural Serbian cohorts compared to urban Belgrade.

Aged↗
PubMed2005

Demographic, environmental, and genetic predictors of metabolic side effects of hydrochlorothiazide treatment in hypertensive subjects.

BACKGROUND: Thiazide diuretics are recommended for first-line treatment of hypertension. Although considered safe and effective, their use is associated with dyslipidemia, hyperglycemia, and an increased risk of developing type 2 diabetes. The aim of this study was to characterize interindividual variation in glucose and lipid responses to hydrochlorothiazide and to identify demographic, environmental, and genetic predictors associated with this variation. METHODS: A community-based sample of 585 adults with essential hypertension (291 African Americans [150 women and 141 men] and 294 non-Hispanic whites [126 women and 168 men]) underwent monotherapy with hydrochlorothiazide for 4 weeks. Linear regression was used to construct prediction models for the changes in plasma total cholesterol, triglyceride, and glucose concentrations. RESULTS: The mean changes (+/- standard deviation) in response to hydrochlorothiazide were 6.13 +/- 22.8 mg/dL for total cholesterol, 17.21 +/- 70 mg/dL for triglycerides, and 3.5 +/- 9.5 mg/dL for plasma glucose. Ethnicity and baseline levels of the analytes were the only predictors that were significant for more than one response. Therefore, the mechanism for these metabolic effects are not entirely shared. CONCLUSIONS: Taken together, demographic, environmental, and genetic factors accounted for only 13% of the total variation in total cholesterol response, 17% of the variation in triglyceride response, and 11% of the variation in glucose response to hydrochlorothiazide, and less than half of this predicted variation in response was explained by measured genotypes.

Adult↗