Maarit Jaana Korhonen

Mercury, Fish Oils, and Risk of Acute Coronary Events and Cardiovascular Disease, Coronary Heart Disease, and All-Cause Mortality in Men in Eastern Finland

Objective— Mercury has been suggested to have negative effects on cardiovascular health. We investigated the effects of high mercury content in hair on the risk of acute coronary events and cardiovascular and all-cause mortality in men from eastern Finland. Methods and Results— The population-based prospective Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) cohort of 1871 Finnish men aged 42 to 60 years and free of previous coronary heart disease (CHD) or stroke at baseline was used. During an average follow-up time of 13.9 years, 282 acute coronary events and 132 cardiovascular disease (CVD), 91 CHD, and 525 all-cause deaths occurred. Men in the highest third of hair mercury content (>2.03 &mgr;g/g) had an adjusted 1.60-fold (95% CI, 1.24 to 2.06) risk of acute coronary event, 1.68-fold (95% CI, 1.15 to 2.44) risk of CVD, 1.56-fold (95% CI, 0.99 to 2.46) risk of CHD, and 1.38-fold (95% CI, 1.15 to 1.66) risk of any death compared with men in the lower two thirds. High mercury content in hair also attenuated the protective effects of high-serum docosahexaenoic acid plus docosapentaenoic acid concentration. Conclusions— High content of mercury in hair may be a risk factor for acute coronary events and CVD, CHD, and all-cause mortality in middle-aged eastern Finnish men. Mercury may also attenuate the protective effects of fish on cardiovascular health.

Polypharmacy Status as an Indicator of Mortality in an Elderly Population

BackgroundIncreased use of drugs has raised concern about the risks of polypharmacy in elderly populations. Adverse outcomes, such as hospitalizations and falls, have been shown to be associated with polypharmacy. So far, little information is available on the association between polypharmacy status and mortality.ObjectiveTo assess whether polypharmacy (six to nine drugs) or excessive polypharmacy (ten or more drugs) could be indicators of mortality in elderly persons.MethodsThis was a population-based cohort study conducted between 1998 and 2003 with mortality follow-up through to 2007. The data in this study were derived from the population-based Kuopio 75+ Study, which involved elderly persons aged ≥75 years living in the city of Kuopio, Finland. The initial sample (sample frame n=4518, random sample n=700) was drawn from the population register. For the purpose of this study, two separate analyses were carried out. In the first phase, participants (aged ≥75 years, n=601) were followed from 1998 (baseline) to 2002. In the second phase, survivors (aged ≥80 years, n=339) were followed from 2003 to 2007. Current medications were determined from drug containers and prescriptions during interviews conducted by a trained nurse. The Kaplan-Meier method and Cox proportional hazards regression were used to examine the association between polypharmacy status and mortality.ResultsIn the first phase, 28% (n=167) belonged to the excessive polypharmacy group, 33% (n=200) to the polypharmacy group, and the remaining 39% (n=234) to the non-polypharmacy (0–5 drugs) group. The corresponding figures in the second phase were 28% (n=95), 39% (n=132) and 33% (n=112), respectively. The mortality rate was 37% in the first phase and 40% in the second phase. In both phases, the survival curves showed a significant difference in all-cause mortality between the three polypharmacy groups. In the first phase, the univariate model showed an association between excessive polypharmacy and mortality (hazard ratio [HR] 2.53, 95% CI 1.83, 3.48); however, after adjustment for demographics and other variables measuring functional and cognitive status, this association did not remain statistically significant (HR 1.28, 95% CI 0.86, 1.91). In the second phase, the association between excessive polypharmacy and mortality (HR 2.23, 95% CI 1.21, 4.12) remained significant after adjustments. Age, male sex and dependency according to the Instrumental Activities of Daily Living screening instrument were associated with mortality in both phases.ConclusionThis study points to the importance of excessive polypharmacy as an indicator for mortality in elderly persons. This association needs to be confirmed following adjustment for co-morbidities.

Patterns of Drug Use and Factors Associated with Polypharmacy and Excessive Polypharmacy in Elderly Persons Results of the Kuopio 75+ Study: A Cross-Sectional Analysis

BackgroundAlthough the increasing use of drugs in elderly persons has raised many concerns in recent years, the process leading to polypharmacy (PP) and excessive polypharmacy (EPP) remains largely unknown.ObjectiveTo describe the number and type of drugs used and to evaluate the role of different factors associated with PP (i.e. 6–9 drugs) and EPP (i.e. ≥10 drugs), with special reference to the number and type of medical diagnoses and symptoms, in a population of home-dwelling elderly persons aged ≥75 years.MethodsThe study was a cross-sectional analysis of a population-based cohort in 1998. The population consisted of home-dwelling elderly persons aged ≥75 years in the city of Kuopio, Finland. The data for the analysis were obtained from the Kuopio 75+ Study, which drew a random sample of 700 elderly residents aged ≥75 years living in the city of Kuopio from the population register. Of these, 601 attended a structured clinical examination and an interview carried out by a geriatrician and a trained nurse in 1998. For this analysis, all home-dwelling elderly participants (n = 523) were included. Study data were expressed as proportions and means with standard deviations. The factors associated with PP and EPP were examined by multinomial logistic regression.ResultsThe most commonly used drugs were cardiovascular drugs (97% in EPP, 94% in PP and 59% in non-PP group) and analgesics (89%, 76% and 54%), respectively. Use of psychotropics was markedly higher in the EPP group (77%) than in the PP (42%) and non-PP groups (20%). The mean number of drugs per diagnosis was 3.6 in the EPP group, 2.6 in the PP group and 1.6 in the non-PP group. Factors associated only with EPP were moderate self-reported health (odds ratio [OR] 2.05; 95% CI 1.08, 3.89), female gender (OR 2.43; 95% CI 1.27, 4.65) and age ≥85 years (OR 2.84; 95% CI 1.41, 5.72). Factors that were associated with both PP and EPP included poor self-reported health (PP: OR 2.15; 95% CI 1.01, 4.59 and EPP: OR 6.02; 95% CI 2.55, 14.20), diabetes mellitus (PP: OR 2.28; 95% CI 1.26, 4.15 and EPP: OR 2.07; 95% CI 1.03, 4.18), depression (PP: OR 2.13; 95% CI 1.16, 3.90 and EPP: OR 2.93; 95% CI 1.51, 5.66), pain (PP: OR 2.69; 95% CI 1.68, 4.30 and EPP: OR 2.74; 95% CI 1.56, 4.82), heart disease (PP: OR 2.51; 95% CI 1.54, 4.08 and EPP: OR 4.63; 95% CI 2.45, 8.74) and obstructive pulmonary disease (including asthma or chronic obstructive pulmonary disease) [PP: OR 2.79; 95% CI 1.24, 6.25 and EPP: OR 6.82; 95% CI 2.87, 16.20].ConclusionsThe study indicates that the factors associated with PP and EPP are not uniform. Age ≥85 years, female gender and moderate self-reported health were factors associated only with EPP, while poor self-reported health and several specific disease states were associated with both PP and EPP. The high number of drugs per diagnosis observed in this study calls for a thorough assessment of the need for and outcomes associated with use of these drugs.

The Nordic prescription databases as a resource for pharmacoepidemiological research—a literature review

All five Nordic countries have nationwide prescription databases covering all dispensed drugs, with potential for linkage to outcomes. The aim of this review is to present an overview of therapeutic areas studied and methods applied in pharmacoepidemiologic studies using data from these databases.

Validity of the Finnish Prescription Register for measuring psychotropic drug exposures among elderly finns: a population-based intervention study.

BackgroundPharmacoepidemiological studies assessing the associations between psychotropic drug use and adverse events in the elderly frequently employ automated pharmacy databases as the source of exposure data. However, information on the validity of these databases for estimating psychotropic drug exposures in elderly people is scarce.ObjectiveThis study evaluated the validity of the Finnish Prescription Register for estimating current exposures to psychotropic drugs in elderly people. Furthermore, the potential change in the validity over time was determined.MethodsThis was a population-based intervention study (GeMS; Geriatric Multidisciplinary Strategy for the Good Care of the Elderly) conducted between 2004 and 2007. Initially, 1000 randomly selected persons aged ≥75 years living in the City of Kuopio, Finland, in November 2003 were invited to participate in the study. Of these, 716 agreed to participate at baseline (2004) and 570 were still available for 3-year follow-up (2007). The validity of the Prescription Register was assessed by comparing it with the self-reported information collected by interviews in 2004 and in 2007 in the GeMS study. Using the self-reported data as a reference standard, sensitivity, specificity and Cohen’s κ statistic (measure of inter-rater agreement for qualitative [categorical] items) with 95% confidence intervals were computed for different categories and subcategories of psychotropic drugs, applying fixed-time windows of 4, 6 and 12 months.ResultsIn 2007, the sensitivity varied between psychotropic categories and subcategories, being generally highest with the 12-month time window (0.57–0.96). The specificity was highest with the 4-month time window (0.94–0.99), showing a slight tendency to decrease with an extended time window. The sensitivity and specificity were highest for antidepressants and antipsychotics, followed by benzodiazepines. The agreement was almost perfect (κ=0.81–1.00) or substantial (κ=0.61–0.80) for all categories and subcategories of psychotropic drugs. Few differences in validity were observed between the two years.ConclusionUsing self-reported data as a reference standard, the Prescription Register provides valid information on current exposures to antidepressants and antipsychotics in elderly people if the time window is selected with adequate consideration. However, the validity is lower for benzodiazepines, suggesting that other sources of information should be considered when performing pharmacoepidemiological studies.

Long-Term Persistence with Statin Therapy: A Nationwide Register Study in Finland

BACKGROUND Preventive statin therapy is often recommended as lifelong treatment. OBJECTIVE The aim of this study was to analyze persistence with statin therapy over a decade of use and to identify factors associated with its discontinuation. METHODS Persistence with therapy among new users of statins in 1995 was followed up until December 31, 2005, in Finland using the nationwide drug reimbursement register. Cumulative persistence was analyzed using Kaplan-Meier analysis. A Cox regression model was applied to analyze associations of various baseline covariates with discontinuation. We further modeled the association of time-specific covariates by stratifying the duration of therapy in years and using a logistic regression in which those continuing therapy until the end of follow-up (persistent users) formed the reference group. Adherence, defined as the proportion of days covered by statins, stratified by the timing of discontinuation, was computed for the respective groups. RESULTS Of the 18,072 new statin users, 73.3% (n =13,254) were aged >54 years and 54.8% (n =9908) were men. Of this cohort, 43.9% (n = 7926) were using statins throughout and at the end of the tenth year. Sex was not associated with persistence at any point. In the Cox model, persons aged 45 to 74 years at initiation were more likely to continue statin use than younger or older age groups. Among those who still used statins after the fifth year of observation, the age difference was not observed in the logistic regression model. The use of 1, 2, 3, or > or =4 cardiovascular drugs before the initiation predicted continuation relative to no cardiovascular drug use (hazard ratio for discontinuation significantly <1.00 in all comparisons). Adherence was best (median 93.9%) among the persistent users. CONCLUSIONS The 10-year persistence with statin use in this general population was approximately 44%. Persons aged 45 to 74 years at initiation and those with at least 1 prescription for another cardiovascular medication were the most likely to continue statin therapy up to the fifth year.

Impact of restricted reimbursement on the use of statins in Finland: a register-based study.

Objectives:New and expensive medicines are a driving force behind growth in medicine costs, and policies promoting use of less expensive products have been widely introduced. This study investigated the short-term consequences of the restricted reimbursement of expensive statins (atorvastatin and rosuvastatin) on the use of statins in Finland. Methods:Data on patients purchasing atorvastatin, rosuvastatin, or simvastatin in 2002–2007 were retrieved from the nationwide Prescription Register. Outcome measures included the time trend in the numbers of purchasers and initiators of different statins, the morbidities of new users before and after the new policy, and the proportion of users of expensive statins switching to other statins. Results:After the restriction, the numbers of purchasers of atorvastatin and rosuvastatin dropped, and atorvastatin and rosuvastatin were seldom prescribed as first-line therapy. Before the restriction, 20.9% of new users of atorvastatin and 18.4% of those of rosuvastatin had either coronary artery disease or familial hyperlipidemia. After the restriction the corresponding figures were 28.7% and 26.8%. After the restriction new users of atorvastatin and rosuvastatin were also more likely to use other cardiovascular medicines or antidiabetics or to have previous statin purchases. A total of 57.6% of those using atorvastatin and 49.2% of those using rosuvastatin before the restriction switched to a less expensive statin. Conclusions:Restricted reimbursement of expensive statins decreased their use. It seems that after the policy new statin treatments have channeled appropriately. Although it is likely that the cost-containment aim of the policy was reached, health and long-term effects are not known.

Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

Background Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial. Design and methods The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46–64 years and free of prior stroke, examined in 1991–1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Results At baseline the mean serum tHcy concentration was 10.9 μmol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23–6.24] for any stroke and 2.61 (95% CI: 1.02–6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (> 11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14–0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15–1.09), compared with men in the lowest third. Conclusion Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.

Functional COMT Val158Met Polymorphism, Risk of Acute Coronary Events and Serum Homocysteine: The Kuopio Ischaemic Heart Disease Risk Factor Study

Background The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD) is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met) in the Catechol-O-methyltransferase (COMT) gene. Methodology and Findings Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middle-aged men from eastern Finland. A population-based prospective cohort of 792 men aged 46–64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR) of 1.73 (95% confidence interval (CI), 1.07–2.79), and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05–2.77). Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93–2.49), subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50–5.76) as compared with other men. Conclusions This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels.

Serum total cholesterol levels and all-cause mortality in a home-dwelling elderly population: a six-year follow-up.

Abstract Objective. To investigate the association between serum total cholesterol and all-cause mortality in elderly individuals aged ≥ 75 years. Design. A prospective cohort study with a six-year follow-up. Setting and subjects. A random sample (n = 700) of all persons aged ≥ 75 years living in Kuopio, Finland. After exclusion of participants living in institutional care and participants using lipid-modifying agents or missing data on blood pressure and cholesterol levels, the final study population consisted of 490 home-dwelling elderly persons with clinical examination. We used the Cox proportional hazard model and the propensity score (PS) method. Main outcome measure. All-cause mortality. Results. In an age- and sex-adjusted analysis, participants with S-TC ≥ 6mmol/l had the lowest risk of death (hazard ratio, HR = 0.48, 95% CI 0.33–0.70) compared with those with S-TC < 5 mmol/l. HR of death for a 1 mmol increase in S-TC was 0.78. In multivariate analyses, the HR of death for a 1 mmol increase in S-TC was 0.82 and using S-TC < 5 mmol/l as a reference, the HR of death for S-TC ≥ 6 mmol/l was 0.59 (95% CI 0.39–0.89) and for S-TC 5.0–5.9 mmol/l, the HR was 0.62 (95% CI 0.42–0.93). In a PS-adjusted model using S-TC < 5 mmol/l as a reference, the HR of death for S-TC ≥ 6 mmol/l was 0.42 (95% CI 0.28–0.62) and for S-TC 5.0–5.9 mmol/l, the HR was 0.57 (95% CI 0.38–0.84). Conclusions. Participants with low serum total cholesterol seem to have a lower survival rate than participants with an elevated cholesterol level, irrespective of concomitant diseases or health status.