Can spirometry improve the performance of cardiovascular risk model in high-risk Eastern European countries?

Aims: Impaired lung function has been strongly associated with cardiovascular disease (CVD) events. We aimed to assess the additive prognostic value of spirometry indices to the risk estimation of CVD events in Eastern European populations in this study. Methods: We randomly selected 14,061 individuals with a mean age of 59 ± 7.3 years without a previous history of cardiovascular and pulmonary diseases from population registers in the Czechia, Poland, and Lithuania. Predictive values of standardised Z-scores of forced expiratory volume measured in 1 s (FEV1), forced vital capacity (FVC), and FEV1 divided by height cubed (FEV1/ht3) were tested. Cox proportional hazards models were used to estimate hazard ratios (HRs) of CVD events of various spirometry indices over the Framingham Risk Score (FRS) model. The model performance was evaluated using Harrell's C-statistics, likelihood ratio tests, and Bayesian information criterion. Results: All spirometry indices had a strong linear relation with the incidence of CVD events (HR ranged from 1.10 to 1.12 between indices). The model stratified by FEV1/ht3 tertiles had a stronger link with CVD events than FEV1 and FVC. The risk of CVD event for the lowest vs. highest FEV1/ht3 tertile among people with low FRS was higher (HR: 2.35; 95% confidence interval: 1.96-2.81) than among those with high FRS. The addition of spirometry indices showed a small but statistically significant improvement of the FRS model. Conclusions: The addition of spirometry indices might improve the prediction of incident CVD events particularly in the low-risk group. FEV1/ht3 is a more sensitive predictor compared to other spirometry indices.

All-cause and cardiovascular mortality in relation to lung function in the full range of distribution across four Eastern European cohorts.

It is unclear whether the dose-response relationship between lung function and all-cause and cardiovascular mortality in the Central and Eastern European populations differ from that reported in the Western European and American populations. We used the prospective population-based HAPIEE cohort that includes randomly selected people with a mean age of 59 ± 7.3 years from population registers in Czech, Polish, Russian and Lithuanian urban centres. The baseline survey in 2002-2005 included 36,106 persons of whom 24,944 met the inclusion criteria. Cox proportional hazards models were used to estimate the dose-response relationship between lung function defined as FEV1 divided by height cubed and all-cause and cardiovascular mortality over 11-16 years of follow-up. Mortality rate increased in a dose-response manner from highest to lower FEV1/height3 deciles. Adjusted hazard ratios (HR) of all-cause mortality for persons in the 8th best, the 5th and the worst deciles were 1.27 (95% CI 1.08‒1.49), 1.37 (1.18-1.60) and 2.15 (1.86‒2.48), respectively; for cardiovascular mortality, the respective HRs were 1.84 (1.29-2.63), 2.35 (1.67-3.28) and 3.46 (2.50‒4.78). Patterns were similar across countries, with some statistically insignificant variation. FEV1/height3 is a strong predictor of all-cause and cardiovascular mortality, across full distribution of values, including persons with preserved lung function.

Impaired lung function and mortality in Eastern Europe: results from multi-centre cohort study.

BACKGROUND: The association between impaired lung function and mortality has been well documented in the general population of Western European countries. We assessed the risk of death associated with reduced spirometry indices among people from four Central and Eastern European countries. METHODS: This prospective population-based cohort includes men and women aged 45-69 years, residents in urban settlements in Czech Republic, Poland, Russia and Lithuania, randomly selected from population registers. The baseline survey in 2002-2005 included 36,106 persons of whom 24,993 met the inclusion criteria. Cox proportional hazards models were used to estimate the hazard ratios of mortality over 11-16 years of follow-up for mild, moderate, moderate-severe and very severe lung function impairment categories. RESULTS: After adjusting for covariates, mild (hazard ratio (HR): 1.25; 95% CI 1.15‒1.37) to severe (HR: 3.35; 95% CI 2.62‒4.27) reduction in FEV1 was associated with an increased risk of death according to degree of lung impairment, compared to people with normal lung function. The association was only slightly attenuated but remained significant after exclusion of smokers and participants with previous history of respiratory diseases. The HRs varied between countries but not statistically significant; the highest excess risk among persons with more severe impairment was seen in Poland (HR: 4.28, 95% CI 2.14‒8.56) and Lithuania (HR: 4.07, 95% CI 2.21‒7.50). CONCLUSIONS: Reduced FEV1 is an independent predictor of all-cause mortality, with risk increasing with the degree of lung function impairment and some country-specific variation between the cohorts.

Antiepileptic drug use and mortality among community-dwelling persons with Alzheimer disease.

OBJECTIVE: To evaluate the risk of death in relation to incident antiepileptic drug (AED) use compared with nonuse in people with Alzheimer disease (AD) through the assessment in terms of duration of use, specific drugs, and main causes of death. METHODS: The MEDALZ (Medication Use and Alzheimer Disease) cohort study includes all Finnish persons who received a clinically verified AD diagnosis (n = 70,718) in 2005-2011. Incident AED users were identified with 1-year washout period. For each incident AED user (n = 5,638), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional regression models and inverse probability of treatment weighting (IPTW). RESULTS: Nearly 50% discontinued AEDs within 6 months. Compared with nonusers, AED users had an increased relative risk of death (IPTW hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.12-1.36). This was mainly due to deaths from dementia (IPTW HR, 1.62; 95% CI, 1.42-1.86). There was no difference in cardiovascular and cerebrovascular deaths (IPTW HR, 0.98; 95% CI, 0.67-1.44). The overall mortality was highest during the first 90 days of AED use (IPTW HR, 2.40; 95% CI, 1.91-3.03). Among users of older AEDs, relative risk of death was greater compared to users of newer AEDs (IPTW HR, 1.79; 95% CI, 1.52-2.16). CONCLUSION: In older vulnerable patients with a cognitive disorder, careful consideration of AED initiation and close adverse events monitoring are needed.

Incidence and Prevalence of Antiepileptic Medication Use in Community-Dwelling Persons with and without Alzheimer's Disease.

BACKGROUND: Although antiepileptic drugs (AEDs) have a potential for adverse drug reactions in older populations, little is known about their use in relation to Alzheimer's disease (AD) diagnosis. OBJECTIVES: In this study, we investigated the incidence and prevalence of AED use in relation to AD diagnosis. METHODS: The MEDALZ-study includes all Finnish persons who received clinically verified AD diagnoses (n = 70,718) during 2005-2011 and a matched comparison cohort without AD (n = 70,718). AD diagnoses were identified from the Special Reimbursement Register. We used the Prescription Register to identify dispensed AEDs. Incident AED users were identified with a one-year washout period 9-10 years before AD diagnosis, and incidence rates per 100 person-years were calculated for each six-month period from nine years before to five years after AD diagnosis. Prevalence was assessed as proportion using AEDs during each six-month time period for incident use. RESULTS: Persons with AD were more likely to use AEDs during the study period (4.3%) than persons without AD (3.2%). The incidence and prevalence of AED use was higher among persons with AD and increased around the time of AD diagnosis. Epilepsy diagnoses did not explain these differences. Persons with AD were more likely to use older AEDs. CONCLUSION: Our study highlights the need to balance effective symptom control with the possible risks of treatment.

Antiepileptic Drug Use and the Risk of Stroke Among Community-Dwelling People With Alzheimer Disease: A Matched Cohort Study.

Background People with Alzheimer disease ( AD ) are more predisposed to seizures than older people in general, and use of antiepileptic drugs ( AED s) is more frequent. AED use has been linked to a higher risk of vascular events in the general population; however, it is not evident whether the same risk exists in people with AD . We assessed the risk of stroke associated with incident AED use among people with AD . Methods and Results The MEDALZ (Medication Use and Alzheimer's Disease) cohort includes all Finnish people who received a clinically verified AD diagnosis (N=70718) from 2005 to 2011. People with previous strokes were excluded. For each incident AED user (n=5617) one nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional hazards models and inverse probability of treatment weighting. Compared with nonuse, AED use was associated with an increased risk of stroke (inverse probability of treatment weighting hazard ratio ( HR ), 1.37; 95% confidence interval [CI], 1.07-1.74). The risk was strongest during the first 90 days (adjusted HR , 2.36; 95% CI , 1.25-4.47) of AED use. According to stroke type, the association was with ischemic strokes (inverse probability of treatment weighting HR , 1.34; 95% CI , 1.00-1.79) and hemorrhagic ones (inverse probability of treatment weighting HR , 1.44; 95% CI , 0.86-2.43). The stroke risk of users of older AED s did not differ from that of the users of newer AED s (adjusted HR , 1.04; 95% CI , 0.71-1.53). Conclusions AED use was related to an increased risk of stroke, regardless of AED type. Our results highlight caution in AED use in this vulnerable population.