Ville L. Langén

Thyroid-stimulating hormone reference range and factors affecting it in a nationwide random sample.

Abstract Background: Previous studies with mainly selected populations have proposed contradicting reference ranges for thyroid-stimulating hormone (TSH) and have disagreed on how screening, age and gender affect them. This study aimed to determine a TSH reference range on the Abbott Architect ci8200 integrated system in a large, nationwide, stratified random sample. To our knowledge this is the only study apart from the NHANES III that has addressed this issue in a similar nationwide setting. The effects of age, gender, thyroid peroxidase antibody (TPOAb)-positivity and medications on TSH reference range were also assessed. Methods: TSH was measured from 6247 participants randomly drawn from the population register to represent the Finnish adult population. TSH reference ranges were established of a thyroid-healthy population and its subpopulations with increasing and cumulative rigour of screening: screening for overt thyroid disease (thyroid-healthy population, n=5709); screening for TPOAb-positivity (risk factor-free subpopulation, n=4586); and screening for use of any medications (reference subpopulation, n=1849). Results: The TSH reference ranges of the thyroid-healthy population, and the risk factor-free and reference subpopulations were 0.4–4.4, 0.4–3.7 and 0.4–3.4 mU/L (2.5th–97.5th percentiles), respectively. Although the differences in TSH between subgroups for age (p=0.002) and gender (p=0.005) reached statistical significance, the TSH distribution curves of the subgroups were practically superimposed. Conclusions: We propose 0.4–3.4 mU/L as a TSH reference range for adults for this platform, which is lower than those presently used in most laboratories. Our findings suggest that intensive screening for thyroid risk factors, especially for TPOAb-positivity, decreases the TSH upper reference limit.

Outcome-Driven Thresholds for Increased Home Blood Pressure Variability

Increased blood pressure (BP) variability predicts cardiovascular disease, but lack of operational thresholds limits its use in clinical practice. Our aim was to define outcome-driven thresholds for increased day-to-day home BP variability. We studied a population-based sample of 6238 individuals (mean age 60.0±12.9, 56.4% women) from Japan, Greece, and Finland. All participants self-measured their home BP on ≥3 days. We defined home BP variability as the coefficient of variation of the first morning BPs on 3 to 7 days. We assessed the association between systolic/diastolic BP variability (as a continuous variable and in deciles of coefficient of variation) and cardiovascular outcomes using Cox regression models adjusted for cohort and classical cardiovascular risk factors, including BP. During a follow-up of 9.3±3.6 years, 304 cardiovascular deaths and 715 cardiovascular events occurred. A 1 SD increase in systolic/diastolic home BP variability was associated with increased risk of cardiovascular mortality (hazard ratio, 1.17/1.22; 95% confidence interval, 1.06–1.30/1.11–1.34; P=0.003/<0.0001) and cardiovascular events (hazard ratio, 1.13/1.14; 95% confidence interval, 1.05–1.21/1.07–1.23; P=0.0007/0.0002). Compared with the average risk in the whole population, risk of cardiovascular deaths (hazard ratio, 1.66/1.84; 95% confidence interval, 1.27–2.17/1.42–2.37; P=0.0002/<0.0001) and events (hazard ratio, 1.46/1.42; 95% confidence interval, 1.21–1.76/1.17–1.71; P<0.0001/0.0004) was increased in the highest decile of systolic/diastolic BP variability (coefficient of variation>11.0/12.8). Increased home BP variability predicts cardiovascular outcomes in the general population. Individuals with a systolic/diastolic coefficient of variation of day-to-day home BP >11.0/12.8 may have an increased risk of cardiovascular disease. These findings could help physicians identify individuals who are at an increased cardiovascular disease risk.

Association between thyroid‐stimulating hormone and blood pressure in adults: an 11‐year longitudinal study

The results of longitudinal studies on the association between thyroid function and blood pressure (BP) are divided. This study aimed to investigate this association in cross‐sectional and longitudinal settings in a nationwide, random sample representative of the Finnish adult population aged 30 and over.

Association of thyroid‐stimulating hormone with lipid concentrations: an 11‐year longitudinal study

Scant data exist on the longitudinal association between thyroid function and lipid concentrations. We investigated associations of TSH and lipid concentrations cross‐sectionally and longitudinally in a nationwide population sample.

Prediction of Blood Pressure and Blood Pressure Change With a Genetic Risk Score.

The authors investigated whether a genetic risk score (GRS) constructed of 32 single nucleotide polymorphisms would predict incident hypertension and blood pressure (BP) change over time in a population cohort during an 11‐year follow‐up (n=5402 at baseline, 3266 at follow‐up). In multivariable models, GRS was associated with higher systolic/diastolic BP values at baseline (β±standard error [SE], 1.04±0.14/1.11±0.13 mm Hg; P<.0001 for both) and at reinvestigation (β±SE, 0.84±0.18/0.79±0.16 mm Hg; P<.0001 for both). Among participants who were normotensive at baseline (n=2045), GRS was not independently associated with systolic/diastolic BP change over time (β±SE, 0.16±0.18/0.20±0.18 mm Hg; P≥.28 for both). In participants in the top tertile of the GRS, as compared with the bottom tertile, the predicted increase in systolic/diastolic BP was 1.18±0.78/0.70±0.49 mm Hg (P=.046/.15) greater and the odds ratio for incident hypertension was 33% higher (P=.03). These data show that GRS is strongly associated with BP but weakly associated with BP increase and incident hypertension in a late middle‐aged population.

Thyroid-stimulating hormone and risk of sudden cardiac death, total mortality and cardiovascular morbidity

Previous data on the association of thyroid function with total mortality, cardiovascular disease (CVD) outcomes and sudden cardiac death (SCD) are conflicting or limited. We investigated associations of thyroid‐stimulating hormone (TSH) with these outcomes in a nationwide population‐based prospective cohort study.

Home versus office blood pressure: longitudinal relations with left ventricular hypertrophy: the Finn-Home study

Objectives: Electrocardiographically assessed left-ventricular hypertrophy (ECG-LVH) is a particularly high-risk phenomenon that is a part of every hypertensive patients initial work-up. Several cross-sectional studies have demonstrated that home blood pressure (BP) has a stronger relation to LVH than office BP. However, longitudinal evidence on the association between home BP and target organ damage is scarce to nonexistent. Methods: We studied in a sample of 615 community-dwelling participants (mean age at baseline 53.7 ± 7.2, 58% women) whether change in home BP is more strongly associated with change in ECG-LVH than change in office BP over an 11-year follow-up. Results: Pearsons correlation coefficients between changes in home/office SBP and changes in Sokolow–Lyon index, Cornell voltage, Cornell product and R wave amplitude in aVL were 0.21/0.18, 0.28/0.17*, 0.25/0.16*, and 0.32/0.20*, respectively (asterisk indicates P < 0.05 for between-method difference in correlations with Steigers z test). For change in home/office DBP and change in the aforementioned ECG-LVH indexes, the correlations were 0.12/0.12, 0.20/0.15, 0.16/0.12, and 0.28/0.19*. Multivariable-adjusted regression modelling provided similar results. No clinically significant increase in correlations between home BP and ECG-LVH indexes occurred after the fourth day of home BP measurement. Conclusion: Our study demonstrates for the first time the superiority of home BP over office BP in the follow-up of left ventricular mass. The results of this and previous studies underline the importance of using out-of-office BP measurements as the primary method for assessing blood pressure levels.

Home and office blood pressure measurements as determinants of kidney disease in the general population: The Finn-Home Study

European and American guidelines for hypertension now advocate out-of-office blood pressure (BP) measurements for diagnosing patients, including those with chronic kidney disease (CKD). Self-monitoring of BP with self-titration of antihypertensive medication has been also shown to improve BP control and to be cost effective in high-risk patients. However, prior inconclusive studies on the association between home BP measurements and CKD have mainly been performed in selected patient populations using a crosssectional approach. It is therefore still unclear whether home BP is more strongly associated with CKD than office BP in the general population. We therefore compared the associations of home and office BP with prevalent albuminuria, incident decreased glomerular filtration rate (GFR), and GFR decline in a nationwide population sample. A total of 2120 participants drawn from the Finnish population register underwent a health examination and home BP monitoring in 2000–2001 as a part of the Health 2000 survey. We excluded 111 participants with missing data from the cross-sectional analyses. The Finn-Home study participants were invited to be re-examined in 2011–2012. A total of 1805 participants who were included in the cross-sectional analyses were still alive and 1350 (74.8%) agreed to participate. We excluded 82 participants with missing data from the longitudinal analyses. All participants underwent a clinical examination with similar methods at baseline and follow-up. Fasting blood samples for serum creatinine were taken and estimated GFRs were calculated. A spot urine sample for albumin and creatinine was only collected at baseline. Office BP was measured twice by a nurse with a mercury sphygmomanometer. Home BP was self-measured twice every morning and evening for seven days using a validated, automatic, oscillometric device. Office and home BP were defined as the means of all available measurements. We examined the association of baseline office and home BP with albuminuria and incident decreased GFR using logistic regression. The association of baseline office and home BP with a change in GFR between baseline and follow-up was assessed using linear regression. Home and office BP were included in all models simultaneously. Multivariable models were adjusted for baseline age, sex, diabetes and smoking as covariates. The longitudinal models also included baseline GFR as a covariate. A total of 2009 participants (mean SD age 56.4 8.5 years; 53.8% women) were included in the analyses for prevalent albuminuria. In the unadjusted models, only systolic and diastolic home BP, but not systolic or diastolic office BP, were associated with prevalent albuminuria (Table 1). In the adjusted model, both systolic home and systolic office BP were associated with prevalent albuminuria. Only diastolic home BP, but not diastolic office BP, was associated with prevalent albuminuria in the adjusted model. A total of 1268 participants (mean SD age 55.2 7.7 years; 55.3% women) with normal GFR at baseline were included in the analyses for incident decreased GFR and GFR change from baseline to follow-up. Baseline systolic home BP, but not systolic office BP, was related to incident decreased GFR in the unadjusted models. (Table 1). No significant association was observed in the unadjusted models between baseline diastolic home BP or diastolic office BP and

[PP.14.11] ELECTROCARDIOGRAPHIC PREDICTORS OF ATRIAL FIBRILLATION IN NORMOTENSIVE AND HYPERTENSIVE INDIVIDUALS

Objective: To study whether the predictive value of electrocardiographic (ECG) abnormalities for atrial fibrillation differs between normotensive and hypertensive individuals. Design and method: We recorded a standard 12-lead ECG and measured blood pressure and other cardiovascular risk factors in a nationwide population sample of 5813 Finns in 2000–2001. We divided the participants into normotensives (blood pressure <140/90 mmHg, n = 3148) and hypertensives (blood pressure > = 140/90 mmHg or use of antihypertensive medications, n = 2665). We followed the participants for incident atrial fibrillation events using nationwide register data. We evaluated the predictive ability of 8 ECG abnormalities for atrial fibrillation in normotensive and hypertensive individuals using Cox regression models adjusted for baseline age, sex, body mass index, smoking, diabetes, coronary heart disease, heart failure, use of chronotropic medication, and heart rate. We tested for interaction between ECG abnormalities and hypertension status. Results: During a mean follow-up of 11.9 ± 2.9 years, 412 participants had > = 1 atrial fibrillation event. Prolonged PR interval predicted atrial fibrillation (Figure) in both normotensive (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.26–4.85; P = 0.009) and hypertensive participants (HR, 1.57; 95% CI, 1.08–2.28; P = 0.019). In normotensive participants, a 20ms increase in corrected QT interval (HR, 1.45; 95% CI 1.15–1.83; P = 0.002) and positive T-wave in lead aVR (HR, 4.06; 95% CI, 1.72–9.58; P = 0.001) were related to atrial fibrillation. In hypertensive participants, left ventricular hypertrophy by Sokolow-Lyon criteria (HR, 1.52; 95% CI, 1.12–2.07; P = 0.008), left axis deviation (HR, 1.58; 95% CI, 1.01–2.46; P = 0.043), and poor R-wave progression (HR, 1.76; 95% CI, 1.15–2.69; P = 0.009) were significant predictors of atrial fibrillation. All previously mentioned ECG abnormalities predicted atrial fibrillation in the whole study population (P< = 0.041 for all). Of all ECG abnormalities, only corrected QT interval was a stronger predictor of atrial fibrillation in normotensive than in hypertensive participants (P for interaction = 0.015). Conclusions: Prolonged PR interval predicts incident atrial fibrillation in both normotensive and hypertensive individuals. The predictive value of ECG abnormalities for atrial fibrillation seems to differ in normotensive and hypertensive individuals only for corrected QT interval. Figure. No caption available.

[OP.7D.02] HOME AND OFFICE BLOOD PRESSURE AS DETERMINANTS OF KIDNEY DISEASE IN THE GENERAL POPULATION: THE FINN-HOME STUDY

Objective: Previous, mainly cross-sectional studies performed in small patient populations have provided inconclusive results on whether home BP is a stronger correlate of prevalent and incident chronic kidney disease than office BP. We therefore compared the associations of home and office BP with prevalent albuminuria, incident decreased glomerular filtration rate (GFR), and decline in GFR in a nationwide population sample. Design and method: We studied a population sample of 2009 participants (56 ± 9 years; 54% women) representative of the Finnish adult population in 2000–2001 and re-examined 1109 individuals 11 years later. We measured office BP, home BP, serum creatinine and spot urine albumin/creatinine ratio at baseline and serum creatinine at follow-up. We estimated GFR of each participant at baseline and follow-up using the Chronic Kidney Disease Epidemiology Collaboration equation. We defined decreased GFR as GFR <60 ml/min/1.73 m2 and albuminuria as a urine albumin/creatinine ratio of >2.5 mg/mmol in men and >3.5 mg/mmol in women. We examined the associations between 1-SD increases in baseline home versus office BP and prevalent albuminuria, incident decreased glomerular filtration rate, and change in GFR from baseline to follow-up using unadjusted logistic and linear regression models. We included home and office BP simultaneously in the models. Results: At baseline, 143 of 2009 (7.1%) participants had albuminuria. Systolic and diastolic home BP were associated with prevalent albuminuria whereas systolic and diastolic office BP were not (Table). Mean GFR change from baseline to follow-up was −9.3 ± 9.8 ml/min/1.73 m2 and 83 of 1109 (7.5%) participants developed decreased GFR during follow-up. Of all BP parameters, only baseline systolic home BP was associated with GFR change and incident decreased GFR (Table). Conclusions: Our results suggest that home BP is more strongly associated with prevalent and incident chronic kidney disease than office BP. Our findings are in line with previous work and support the superiority of home BP over office BP. Figure. No caption available.