Serial blood pressure measurements, left ventricular remodelling and cardiovascular outcomes.

BACKGROUND: Hypertension is a risk factor for the development of cardiovascular disease. Whether serial blood pressure (BP) measurements are more closely associated with subclinical left ventricular (LV) remodelling and better predict risk of cardiovascular events over individual BP measurements are not known. METHODS: We assessed systolic BP, diastolic BP and pulse pressure at several time points during adulthood in 1333 women and 1211 men participating in the Akershus Cardiac Examination 1950 Study. We defined serial BP measurements as the sum of averaged BPs from adjacent consecutive visits indexed to total exposure time between measurements. We assessed the associations between serial and individual BP measurements and (1) LV structure, function and volumes and (2) incident myocardial infarction, ischemic stroke, heart failure and cardiovascular death. RESULTS: All indices of higher serial BP measurements were associated with increased indexed LV mass, and the associations were stronger than those of individual BP measurements. Serial diastolic BP pressure was strongly and inversely associated with LV systolic function, while higher serial systolic BP was primarily associated with higher LV volumes. Both serial systolic (incidence rate ratio [IRR] 1.10, 95% CI 1.03 to 1.17) and diastolic BPs (IRR 1.14, 95% CI 1.02 to 1.27) were associated with increased incidence of clinical events. CONCLUSION: In healthy community dwellers without established cardiovascular disease, different serial BP indices associate strongly with LV remodelling and cardiovascular outcomes. Whether the use of serial BP indices for guiding treatment is superior to individual measurements should be explored in additional prospective studies.

B-Type Natriuretic Peptide Is Associated with Indices of Left Ventricular Dysfunction in Healthy Subjects from the General Population: The Akershus Cardiac Examination 1950 Study.

BACKGROUND: Concentrations of B-type natriuretic peptide (BNP) reflect myocardial distension and stress, and are associated with poor prognosis in patients with cardiovascular disease. Accordingly, we hypothesized that concentrations of BNP would be associated with indices of adverse left ventricular (LV) remodeling and early stages of LV systolic and diastolic dysfunction in healthy participants from the general population. METHODS: We measured BNP in 1757 women and 1677 men free from known coronary heart disease participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants underwent extensive cardiovascular phenotyping at baseline, including detailed echocardiography with assessment of indexed LV mass (LVMI), diastolic [tissue Doppler e', E/e' ratio, indexed left atrial volume (LAVI), maximal tricuspid regurgitation velocity (TRVmax), and E/A ratio], and systolic [global longitudinal strain (GLS) and LV ejection fraction (LVEF)] function. RESULTS: Study participants with the highest BNP concentrations had higher GLS, LVMI, e', E/e' ratio, LAVI, TRVmax, and E/A ratio. In adjusted analyses, both GLS and LVEF exhibited significant nonlinear associations with BNP, with reduced LV systolic function observed in both the low and high concentration range of BNP. CONCLUSIONS: In healthy participants recruited from the general population, concentrations of BNP exhibit nonlinear associations with LV systolic function, and both low and high concentrations are associated with reduced LV systolic function. This supports the notion that natriuretic peptides are beneficial and elicit cardioprotective effects, and may have important implications for the interpretation of BNP measurements in the general population.

Cardiac Troponin I and T Are Associated with Left Ventricular Function and Structure: Data from the Akershus Cardiac Examination 1950 Study.

BACKGROUND: Concentrations of cardiac troponin I (cTnI) and T (cTnT) are associated with clinical cardiac outcomes, but do not correlate closely in subjects recruited from the general population. Accordingly, we hypothesized that cTnI and cTnT concentrations would be influenced by different cardiovascular (CV) and non-CV risk factors and reflect different CV phenotypes. METHODS: We measured cTnI and cTnT with last generation assays in 1236 women and 1157 men with no known CV disease participating in the prospective observational Akershus Cardiac Examination 1950 Study. All study participants underwent extensive CV phenotyping at baseline, including detailed echocardiography. RESULTS: Concentrations of cTnI were measurable in 60.3% and cTnT in 72.5% of study participants (P < 0.001), and correlated moderately (r = 0.53; P < 0.001). cTnI was more strongly associated with male sex (P = 0.018), higher education (P < 0.001), history of hypertension (P < 0.001), and age (P < 0.001), whereas cTnT was more strongly associated with eGFR (P = 0.015). Both cTnI and cTnT were inversely associated with global longitudinal strain and positively associated with LV mass index (LVMI) in analyses adjusted for CV risk factors. The association between cTnI and LVMI was stronger than the association between cTnT and LVMI (P = 0.035). Concentrations of cTnI improved diagnostic accuracy for LV hypertrophy when added to established CV risk factors, but concentrations of cTnT did not improve these models further. CONCLUSIONS: In a large community-based cohort examined with extensive echocardiography, concentrations of cTnI and cTnT are associated with subclinical LV hypertrophy and dysfunction. Concentrations of cTnI appear superior to cTnT in predicting subclinical LV hypertrophy.

Prediction of incident atrial fibrillation with cardiac biomarkers and left atrial volumes.

OBJECTIVE: Atrial fibrillation is a common arrhythmia associated with risk of stroke, heart failure and death. We aimed to elucidate the associations of cardiac biomarkers, echocardiographic left atrial volumetric indices and risk of prevalent and incident atrial fibrillation in the general population. METHODS: We assessed cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), maximum (LAVimax) and minimum (LAVimin) indexed left atrial volumes and left atrial emptying fraction (LAEF) in subjects born in 1950 participating in the prospective observational cohort, Akershus Cardiac Examination 1950 Study. The Cohorts for Heart and Ageing Research in Genomic Epidemiology for Atrial Fibrillation risk score and sex was used to adjust for residual risk of atrial fibrillation. RESULTS: Out of 3487 subjects, 157 (4.5%) had prevalent and 123 (3.5%) had incident atrial fibrillation. Echocardiographic left atrial volumes and cardiac biomarkers associated with prevalent atrial fibrillation, but GDF-15 was non-significant in adjusted analysis. Incident atrial fibrillation was predicted by LAVimax (adjusted HR 1.51, 95% CI 1.30 to 1.75), LAVimin (adjusted HR 1.52, 95% CI 1.35 to 1.72), LAEF (adjusted HR 1.24, 95% CI 1.04 to 1.48) and NT-proBNP (adjusted HR 1.57, 95% CI 1.32 to 1.85). cTnT and NT-proBNP provided incremental prognostic information to left atrial volumes, but GDF-15 demonstrated no prognostic value for incident atrial fibrillation. CONCLUSIONS: In the general population, echocardiographic left atrial volumetric indices and NT-proBNP, but not cTnT and GDF-15, associate with prevalent atrial fibrillation and with risk of incident atrial fibrillation. cTnT and NT-proBNP provide incremental prognostic information to echocardiography.

Impact of Blood Pressure in the Early 40s on Left Atrial Volumes in the Mid-60s: Data From the ACE 1950 Study.

Background Echocardiographic measures of left atrial volumes are powerful predictors of cardiovascular events and important for assessing diastolic dysfunction. Despite this, there is limited knowledge of factors influencing left atrial remodeling. In particular, the impact of blood pressure in those in their early 40s on left atrial volumes later in life has not been sufficiently elucidated. Methods and Results We linked data from individuals born in 1950 who participated in the Age 40 Program, and the ACE (Akershus Cardiac Examination) 1950 Study. We divided the study population into quartiles of systolic blood pressure in their early 40s and assessed the proportion of individuals with an enlarged left atrium in their mid-60s. The associations between blood pressure and left atrial volumes were assessed in linear regression analyses. Of the 2591 individuals included in this study, 1302 (50.3%) were women, and the mean age in the Age 40 Program was 40.1±0.3 years. Systolic blood pressure was 128.1±13.6 mm Hg and diastolic blood pressure was 78.3±9.5 mm Hg. Mean age in the ACE 1950 Study was 64.0±0.6 years. The proportion of individuals with an enlarged left atrium increased across the quartiles of systolic blood pressure (P=0.001). Systolic blood pressure was independently associated with left atrial volumes; the end-systolic volume was 0.09 mL (95% CI, 0.04-0.14 mL) larger per 1-mm Hg higher systolic blood pressure. Conclusions Our findings suggest that increased blood pressure in those in their early 40s is relevant for left atrial remodeling later in life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01555411.

Sex differences and higher upper normal limits for left atrial end-systolic volume in individuals in their mid-60s: data from the ACE 1950 Study.

AIMS: The current study aimed to describe normal values of left atrial (LA) volumes and LA emptying fraction (LAEF) in a large sample in their mid-60s from the general population and to explore sex differences. METHODS AND RESULTS: In the Akershus Cardiac Examination (ACE) 1950 Study, body surface area-indexed LA maximum (LAVimax) and minimum (LAVimin) volumes and LAEF were measured in 3489 individuals aged 63.9 ± 0.6 years from the general population. A healthy group of 832 individuals was defined. Data are presented as mean ± standard deviation (SD) and a normal range of mean ± 2 SD. T-tests were used for comparisons. In the healthy group, mean LAVimax was 25.5 ± 6.2 mL/m2 and the normal range was 13.1-37.9 mL/m2. Men had significantly larger body surface area-indexed volumes than women, but there was no difference in LAEF. The mean LAVimax for healthy men was 26.4 ± 6.5 mL/m2, for healthy women 24.9 ± 5.8 mL/m2 (P < 0.001) and the upper normal limits were 39.4 and 36.5 mL/m2, respectively. In the healthy group, 13.0% of all men and 5.4% of all women had LAVimax above the current upper normal limit of 34 mL/m2. CONCLUSION: A large proportion of healthy individuals, in particular men, had LAVimax >34 mL/m2. Our findings suggest that the recommended cut-off may be too low at the age of 65 years and above and that sex-specific cut-offs should be considered.

Mechanical dispersion as a marker of left ventricular dysfunction and prognosis in stable coronary artery disease.

Assessment of global longitudinal strain (GLS) is superior to ejection fraction (EF) in the evaluation of left ventricular (LV) function in patients with stable coronary artery disease (CAD). However, the role of mechanical dispersion (MD) in this context remains unresolved. We aimed to evaluate the potential role of MD as a marker of LV dysfunction and long-term prognosis in stable CAD. EF, GLS and MD were assessed in 160 patients with stable CAD, 1 year after successful coronary revascularization. Serum levels of high-sensitivity cardiac troponin I (hs-cTnI) and amino-terminal pro B-type natriuretic peptide (NT-proBNP) were quantified as surrogate markers of LV dysfunction. The primary endpoint was defined as all-cause mortality, the secondary endpoint was defined as the composite of all-cause mortality and hospitalization for acute myocardial infarction or heart failure during follow-up. Whereas no associations between EF and the biochemical markers of LV function were found, both GLS and MD correlated positively with increasing levels of hs-cTnI (R = 0.315, P < 0.001 and R = 0.442, P < 0.001, respectively) and NT-proBNP (R = 0.195, P = 0.016 and R = 0.390, P < 0.001, respectively). Median MD was 46 ms (interquartile range [IQR] 37-53) and was successfully quantified in 96% of the patients. During a median follow-up of 8.4 (IQR 8.2-8.8) years, 14 deaths and 29 secondary events occurred. MD was significantly increased in non-survivors, and provided incremental prognostic value when added to EF and GLS. NT-proBNP was superior to the echocardiographic markers in predicting adverse outcomes. MD may be a promising marker of LV dysfunction and adverse prognosis in stable CAD.

Prevalence of atrial fibrillation and cardiovascular risk factors in a 63-65 years old general population cohort: the Akershus Cardiac Examination (ACE) 1950 Study.

OBJECTIVES: To investigate the sex-specific prevalence of atrial fibrillation (AF), including subclinical AF found by screening in a general population aged 63-65 years. The prevalence of cardiovascular risk factors and their association with AF will also be investigated. DESIGN: Cross-sectional analysis of an observational, prospective, longitudinal, population-based cohort study. SETTING: General population in Akershus county, Norway. PARTICIPANTS: Women and men born in 1950. We included 3706 of 5827 eligible individuals (63.6%); 48.8% were women. METHODS: All participants underwent extensive cardiovascular examinations, including 12-lead ECG. History of AF and other cardiovascular diseases were self-reported. Subsequent validation of all reported or detected AF diagnoses was performed. RESULTS: Mean age was 63.9±0.7 years. Prevalence of ECG-verified AF was 4.5% (women 2.4%, men 6.4%; p<0.001), including screen-detected AF in 0.3% (women 0.1%, men 0.6%; p<0.01). Hypertension was found in 62.0% (women 57.8%, men 66.0%; p<0.001). Overweight or obesity was found in 67.6% (women 59.8%, men 74.9%; p<0.001). By multivariate logistic regression, risk factors associated with AF were height (OR 1.67 per 10 cm; 95% CI 1.26 to 2.22; p<0.001), weight (OR 1.15 per 10 kg; 95% CI 1.01 to 1.30; p=0.03), hypertension (OR 2.49; 95% CI 1.61 to 3.86; p<0.001), heart failure (OR 3.51; 95% CI 1.71 to 7.24; p=0.001), reduced estimated glomerular filtration rate (OR 2.56; 95% CI 1.42 to 4.60; p<0.01) and at least one first-degree relative with AF (OR 2.32; 95% CI 1.63 to 3.31; p<0.001), whereas male sex was not significantly associated (OR 1.00; 95% CI 0.59 to 1.68; p=0.99). CONCLUSION: In this cohort from the general population aged 63-65 years, we found a higher prevalence of known AF than previously reported below the age of 65 years. The additional yield of single time point screening for AF was low. Body size and comorbidity may explain most of the sex difference in AF prevalence at this age. TRIAL REGISTRATION NUMBER: NCT01555411; Results.