Non-potassium sparing diuretics and sudden cardiac death in hypertensive patients : a pharmacoepidemiologic approach

The studies described in this thesis focus on the possible relationship between the use of non-potassium sparing diuretics and the occurrence of sudden cardiac death in hypertensive patients. To study this potential adverse drug reaction several methods were applied, including estimates of population attributable proportions, a meta-analysis and, most importantly, a case-referent (case-control) study. In this chapter the main conclusions, their possible implications and suggestions for future research will be give

Instrumental Variables in Influenza Vaccination Studies:Mission Impossible?!

AbstractObjectivesUnobserved confounding has been suggested to explain the effect of influenza vaccination on mortality reported in several observational studies. An instrumental variable (IV) is strongly related to the exposure under study, but not directly or indirectly (through other variables) with the outcome. Theoretically, analyses using IVs to control for both observed and unobserved confounding may provide unbiased estimates of influenza vaccine effects. We assessed the usefulness of IV analysis in influenza vaccination studies.MethodsInformation on patients aged 65 years and older from the computerized Utrecht General Practitioner (GP) research database over seven influenza epidemic periods was pooled to estimate the association between influenza vaccination and all-cause mortality among community-dwelling elderly. Potential IVs included in the analysis were a history of gout, a history of orthopaedic morbidity, a history of antacid medication use, and GP-specific vaccination rates.ResultsUsing linear regression analyses, all possible IVs were associated with vaccination status: risk difference (RD) 7.8% (95% confidence interval [CI] 3.6%; 12.0%), RD 2.8% (95% CI 1.7%; 3.9%), RD 8.1% (95% CI 6.1%; 10.1%), and RD 100.0% (95% CI 89.0%; 111.0%) for gout, orthopaedic morbidity, antacid medication use, and GP-specific vaccination rates, respectively. Each potential IV, however, also appeared to be related to mortality through other observed confounding variables (notably age, sex, and comorbidity).ConclusionsThe potential IVs studied did not meet the necessary criteria, because they were (indirectly) associated with the outcome. These variables may, therefore, not be suited to assess unconfounded influenza vaccine effects through IV analysis

Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study

BACKGROUND: Noninvasive assessment of intima-media thickness (IMT) is widely used in observational studies and trials as an intermediate or proxy end point for cardiovascular disease. However, data showing that IMT predicts cardiovascular disease are limited. We studied whether common carotid IMT is related to future stroke and myocardial infarction. METHODS AND RESULTS: We used a nested case-control approach among 7983 subjects aged > or =55 years participating in the Rotterdam Study. At baseline (March 1990 through July 1993), ultrasound images of the common carotid artery were stored on videotape. Determination of incident myocardial infarction and stroke was predominantly based on hospital discharge records. Analysis (logistic regression) was based on 98 myocardial infarctions and 95 strokes that were registered before December 31, 1994. IMT was measured from videotape for all case subjects and a sample of 1373 subjects who remained free from myocardial infarction and stroke during follow-up. The mean duration of follow-up was 2.7 years. Results were adjusted for age and sex. Stroke risk increased gradually with increasing IMT. The odds ratio for stroke per standard deviation increase (0.163 mm) was 1.41 (95% CI, 1.25 to 1.82). For myocardial infarction, an odds ratio of 1.43 (95% CI, 1.16 to 1.78) was found. When subjects with a previous myocardial infarction or stroke were excluded, odds ratios were 1.57 (95% CI, 1.27 to 1.94) for stroke and 1.51 (95% CI, 1.18 to 1.92) for myocardial infarction. Additional adjustment for several cardiovascular risk factors attenuated these associations: 1.34 (95% CI, 1.08 to 1.67) and 1.25 (95% CI, 0.98 to 1.58), respectively. CONCLUSIONS: The present study, based on a short follow-up period, provides evidence that an increased common carotid IMT is associated with future cerebrovascular and cardiovascular events

Higher prevalence of depressive symptoms in middle-aged men with low serum cholesterol levels

OBJECTIVE: Investigators from several studies have reported a positive relationship between low cholesterol levels and death due to violent causes (eg, suicide and accidents), possibly mediated by depressive symptoms, aggression or hostility, or impulsivity. We set out to establish whether middle-aged men with chronically low cholesterol levels (< or =4.5 mmol/liter) have a higher risk of having depressive symptoms, according to scores on the Beck Depression Inventory, compared with a reference group of men with cholesterol levels between 6 and 7 mmol/liter. A similar comparison was also made for measures of anger, hostility, and impulsivity. METHODS: Cholesterol measurements were obtained as part of a population-based cholesterol screening study in 1990-1991. These levels were remeasured in 1993-1994. Only those whose cholesterol level remained in the same range were included in the study. Depressive symptoms were assessed by using the Beck Depression Inventory; anger, by questionnaires based on the Spielberger Anger Expression Scale and State-Trait Anger Scale; hostility, by the Buss-Durkee Hostility Inventory; and impulsivity, by the Eysenck and Eysenck Impulsivity Questionnaire. RESULTS: Men with chronically low cholesterol levels showed a consistently higher risk of having depressive symptoms (Beck Depression Inventory score > or =15 or > or =17) than the reference group, even after adjusting for age, energy intake, alcohol use, and presence of chronic diseases. No differences in anger, hostility, and impulsivity were observed between the two groups. CONCLUSIONS: Men with a lower cholesterol level (< or =4.5 mmol/liter) have a higher prevalence of depressive symptoms than those with a cholesterol level between 6 and 7 mmol/liter. These data may be important in the ongoing debate on the putative association between low cholesterol levels and violent death

Long-term prognostic importance of a single pulmonary wedge pressure measurement after myocardial infarction: A ten-year follow-up study

To assess the influence on short- and long-term survival of haemodynamic variables measured after acute myocardial infarction, a 10-year prospective follow-up study was undertaken. A total of 304 patients (259 males, 45 females) discharged from hospital after myocardial infarction and under 66 years of age were studied. Haemodynamic variables measured shortly after admittance included pulmonary wedge pressure, mixed venous oxygen saturation, blood pressure and heart rate. In the analysis, adjustments were made for differences in age, gender, clinical parameters and cardiovascular risk factors. Pulmonary wedge pressure was found to be a strong and independent predictor of both short-term and long-term survival. A gradual increase of the 10-year mortality risk with elevated wedge pressure could be demonstrated (relative risk, 1.09/mmHg; 95% confidence interval, 1.04–1.15). Relative risks of patients in the three highest categories of wedge pressure, 12–15 mmHg, 15–19 mmHg and 19 mmHg and higher, compared with patients in the lowest category, lower than 12 mmHg, were 2.25 (95% CI, 1.11–4.55), 2.43 (95% CI, 1.20–4.92) and 2.57 (95% CI, 1.04–6.37), respectively. The other measured haemodynamic variables were found to be associated with short-term mortality only. In conclusion, haemodynamic measurements after myocardial infarction are of prognostic importance after discharge. A single measurement of an elevated wedge pressure in particular unfavourably influenced both short-term and long-term survival

Yield of screening for atrial fibrillation in primary care with a hand-held, single-lead electrocardiogram device during influenza vaccination

Aims To assess the yield of screening for atrial fibrillation (AF) with a hand-held single-lead electrocardiogram (ECG) device during influenza vaccination in primary care in the Netherlands. Methods and results We used the MyDiagnostick to screen for AF in persons who participated in influenza vaccination sessions of ten Dutch primary care practices. In case of suspected AF detection by the stick, the recorded 1-min ECG registrations were analysed by a cardiologist. We scrutinized electronic medical files of the general practitioners to obtain information about the cases screened. Multivariable logistic regression analysis was performed to predict the relation between patient characteristics and a new screen-detected diagnosis of AF. In total, 3269 persons were screened for AF during the influenza vaccination sessions of 10 general practitioner practices. As a result, 37 (1.1%) new cases of AF were detected. Prior transient ischeamic attack or stroke (OR 6.05; 95%CI 1.93-19.0), and age (OR 1.09 per year; 95% CI 1.05-1.14) were independent predictors for such newly screen-detected AF. Of the 37 screen-detected AF cases, 2.7% had a CHA2DS2-VASc of 0, 18.9% a score of 1, and 78.4% a score of 2 or more. The majority needed oral anticoagulant therapy. Conclusions Screening seems feasible with an easy to use single-lead, hand-held ECG device with automatic AF detection during influenza vaccination in primary care and results in a '1-day' yield of 1.1% new cases of AF. Trial registration clinicaltrials.gov NCT02006524

Peripheral arterial disease in the elderly: The Rotterdam Study

To assess the age- and sex-specific prevalence of peripheral arterial disease (PAD) and intermittent claudication (IC) in an elderly population, we performed a population-based study in 7715 subjects (40% men, 60% women) aged 55 years and over. The presence of PAD and IC was determined by measuring the ankle-arm systolic blood pressure index (AAI) and by means of the World Health Organization/Rose questionnaire, respectively. PAD was considered present when the AAI was <0.90 in either leg. The prevalence of PAD was 19.1% (95% confidence interval, 18.1% to 20.0%): 16.9% in men and 20.5% in women. Symptoms of IC were reported by 1.6% (95% confidence interval, 1.3% to 1.9%) of the study population (2.2% in men, 1.2% in women). Of those with PAD, 6.3% reported symptoms of IC (8.7% in men, 4.9% in women), whereas in 68.9% of those with IC an AAI below 0.90 was found. Subjects with an AAI <0.90 were more likely to be smokers, to have hypertension, and to have symptomatic or asymptomatic cardiovascular disease compared with subjects with an AAI of 0.90 or higher. The authors conclude that the prevalence of PAD in the elderly is high whereas the prevalence of IC is rather low, although both prevalences clearly increase with advancing age. The vast majority of PAD patients reports no symptoms of IC

Determinants of first prescription of hormone replacement therapy. A follow-up study among 1689 women aged 45-60 years

The aim of the present study was to ascertain the cumulative incidence of first hormone replacement therapy (HRT) and the factors that predict its prescription. In a general population 1689 women were followed for 9 months in order to trace first HRT prescriptions. Determinants (well-being, attitude towards menopause, menopausal status and another 9 variables) were measured by means of a questionnaire. Data analyses were performed for all women and for women with or without typical climacteric complaints. The cumulative 9 month incidence of HRT was 6.2%. For women without typical complaints a lower level of well-being (odds ratio 5.5; 95% Cl 1.9–15.5) and the former use of the contraceptive pill (odds ratio 4.6; 95% CI 1.0–20.5) were independently associated with HRT prescription. For women with typical complaints a positive attitude towards ‘menopause should be treated' (odds ratio 3.8; 95% Cl 1.8–8.0) was a determinant of HRT prescription. The cumulative incidence of HRT prescription is high, but from additional data it is apparent that within a period of 1 year and 9 months the majority of women stop taking HRT. For women without typical complaints, physicians prescribe HRT five times more often to those with a lower level of well-being. For women with typical complaints the physician's prescription is primarily related to the woman's attitude towards (medical) treatment of the menopause