Nighttime ambulatory pulse pressure predicts cardiovascular and all-cause mortality among middle-aged participants in the 21-year follow-up

Office pulse pressure (PP) is a predictor for cardiovascular (CV) events and mortality. Our aim was to evaluate ambulatory PP as a long-term risk factor in a random cohort of middle-aged participants. The Opera study took place in years 1991-1993, with a 24-h ambulatory blood pressure measurement (ABPM) performed to 900 participants. The end-points were non-fatal and fatal CV events, and deaths of all-causes. Follow-up period, until the first event or until the end of the year 2014, was 21.1 years (mean). Of 900 participants, 22.6% died (29.6% of men/15.6% of women, p<.001). A CV event was experienced by 208 participants (23.1%), 68.3% of them were male (p<.001). High nighttime ambulatory PP predicted independently CV mortality (hazard ratio [HR] 2.60; 95% confidence interval [CI 95%] 1.08-6.31, p=.034) and all-cause mortality in the whole population (HR 1.72; Cl 95% 1.06-2.78, p=.028). In males, both 24-h PP and nighttime PP associated with CV mortality and all-cause mortality (24-h PP HR for CV mortality 2.98; CI 95% 1.11-8.04, p=.031 and all-cause mortality HR 2.40; CI 95% 1.32-4.37, p=.004). Accordingly, nighttime PP; HR for CV mortality 3.13; CI 95% 1.14-8.56, p=.026, and for all-cause mortality HR 2.26; CI 95% 1.29-3.96, p=.004. Cox regression analyses were adjusted by sex, CV risk factors, and appropriate ambulatory mean systolic BP. In our study, high ambulatory nighttime PP was detected as a long-term risk factor for CV and all-cause mortality in middle-aged individuals

Gender differences in prevalence and prognostic value of fragmented QRS complex

Background: Fragmented QRS (fQRS) on 12-lead electrocardiogram(ECG) is associated with scarred myocardium and adverse outcome. However, the data on gender differences in terms of its prevalence and prognostic value is sparse. The aim of this study was to evaluate whether gender differences in fQRS exist among subjects drawn from populations with different risk profiles. Methods: We analyzed fQRS from 12-lead ECG in 953 autopsy-confirmed victims of sudden cardiac death (SCD) (78% men; 67.0 +/- 11.4 yrs), 1900 coronary artery disease (CAD) patients with angiographically confirmed stenosis of >= 50% (70% men; 66.6 +/- 9.0 yrs, 43% with previous myocardial infarction [MI]), and in 10,904 adults drawn from the Finnish adult general population (52% men; 44.0 +/- 8.5 yrs). Results: Prevalence of fQRS was associated with older age, male sex and the history and severity of prior cardiac disease of subjects. Among the general population fQRS was more commonly found among men in comparison to women (20.5% vs. 14.8%, p <0.001). The prevalence of fQRS rose gradually along with the severity of prior cardiac disease in both genders, yet remained significantly higher in the male population: subjects with suspected or known cardiac disease (25.4% vs. 15.8% p <0.001), CAD patients without prior MI (39.9% vs. 26.4%, p <0.001), CAD patients with prior MI (42.9% vs. 31.2%, p <0.001), and victims of SCD (56.4% vs. 44.4%, p <0.001). Conclusions: The prevalence of QRS fragmentation varies in different populations. The fragmentation is clearly related to the underlying cardiac disease in both genders, however women seem to have significantly lower prevalence of fQRS in each patient population in comparison to men. (C) 2020 The Authors. Published by Elsevier Inc.Peer reviewe

Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.</p

Cancer increases the risk of atrial fibrillation during long-term follow-up (OPERA study)

Abstract Introduction: Relation between atrial fibrillation (AF) and cancer is known but not very well understood. The purpose of this prospective study was to find out whether subjects with cancer were at greater risk of AF than subjects without cancer. Materials and methods: The study was based on the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) material and had 1045 subjects and the mean follow-up time of 16.3 years. During the follow-up AF and cancer diagnosis were made (atrial flutter included) if these events were listed in the National Death Registry and/or hospital discharge registry. Results: In this study 130 subjects (12%) had cancer and 19% of these had AF, whereas only 9% of those without cancer experienced AF during the follow-up (p&lt;0.001). Subjects in the cancer group had greater probability of developing atrial fibrillation during the follow-up time in comparison to the subjects without cancer (Hazard ratio (HR) 2.47 (95%CI) 1.57–3.88) in multivariate model including relevant confounding factors. Conclusion: The main finding of this OPERA study was that cancer is an independent risk factor of atrial fibrillation. Still it remains unclear whether this association is causative or whether cancer and atrial fibrillation just share the same pathophysiologic mechanisms

Non-dipping blood pressure pattern and new-onset diabetes in a 21-year follow-up

Purpose: Non-dipping blood pressure (BP) pattern has been associated with metabolic changes and cardiovascular events. With regard of diabetes, studies are scarce. Our aim was to investigate if there is an association between changes in dipping patterns and incidence of diabetes. Materials and methods: A 24-h ambulatory BP measurement was recorded in addition to other laboratory measurements, and a questionnaire and physical examination were carried out in the baseline study and after 21-year follow-up among a study population (n = 449) consisting of randomly selected middle-aged Finnish females and males without diabetes. Results: 128 (28.5%) developed diabetes during the follow-up. The incidence of new-onset diabetes was the highest, 41.0%, among those subjects who were non-dippers (their systolic BP declined <10% from daytime to nighttime) in the baseline and also in the follow-up study, while the incidence of diabetes was 19.6% in the dipper – dipper (a nighttime decline of systolic BP 10% or more) group (p = 0.003). The difference remained statistically significant after adjustment with age, sex, body mass index, fasting glucose, triglycerides, and insulin levels, smoking status, 24-h mean systolic BP, high-sensitivity C-reactive protein, estimated glomerular filtration and diuretics use. In logistic regression analysis, the non-dipper – non-dippers were at higher risk of diabetes compared with dipper – dipper group (OR = 2.27, 95% CI: 1.13–4.56, p = 0.022). Conclusions: Our prospective study shows that there is an independent association between non-dipping BP pattern and the incidence of diabetes in a 21-year follow-up

Smoking cessation and obesity-related morbidities and mortality in a 20-year follow-up study

Background Smoking is the biggest preventable factor causing mortality and morbidity and the health benefits of smoking cessation are commonly known. Smoking cessation-related weight gain is well documented. We evaluated the association between smoking cessation and the incidence of obesity-related morbidities such as hypertension, diabetes and metabolic syndrome as well as mortality. We also evaluated telomere length related to smoking cessation. Material and methods This study was part of the OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. The mean follow up time among the 600 study subjects was 20 years. We divided the study subjects into four groups by smoking status (“never”, “current”, “ex-smokers” and “quit”) and analyzed their health status. “Ex-smokers” had quit smoking before baseline and “quit” quit during the follow-up time. Information about total mortality between the years 2013–2020 was also utilized. Results During the follow-up time systolic blood pressure decreased the most in the “current” and in the “ex-smoker” groups. Office SBP decreased the least in the “quit” group (p = 0.001). BMI increased the most in the “quit” and the least in the “ex-smokers” group (p = 0.001). No significant increases were seen in the incidence of obesity-related-diseases, such as metabolic syndrome, hypertension and diabetes was seen. There was no significant difference in the shortening of telomeres. Odds of short-term mortality was increased in the “current” group (2.43 (CI 95% 1.10; 5.39)), but not in the “quit” (1.43 (CI 95% 0.73–2.80)) or “ex-smoker” (1.02 (CI 95% 0.56–1.86)) groups when compared to “never” group. Conclusions Even though, the blood pressure levels were unfavorable in the “quit” group, there was no significant increase in the incidence of obesity-related-diseases, and a noticeable benefit in short-term mortality was seen during the 6-year follow-up. The benefits of smoking cessation outweigh the disadvantages in the long-term

Leisure time and occupational physical activity, overall and cardiovascular mortality: a 24-year follow-up in the OPERA study

AbstractBackground In earlier studies, the health benefits of physical activity have only been related to leisure time physical activity (LTPA). High occupational physical activity (OPA) might even be harmful. The current physical activity recommendations do not separate the OPA and LTPA. We investigated the effect of LTPA and OPA on cardiovascular morbidity and mortality during long-term follow-up. We also examined how heavy work affects the benefits of leisure time exercise.Material and methods The study was part of the OPERA study and the baseline examinations were conducted between the years 1991 and 1993. The Follow-up of events continued until the end of the year 2020. Study subjects (n = 1044) were divided into four groups according to their LTPA (“no exercise”, “irregular”, “regular” and “heavy regular”) and into three groups according to their OPA (“no activity”, “mild” and “heavy”). The amount of exercise was self-reported and the exercise status was defined at the beginning of the study. Study subjects were followed up for their overall mortality (26 years), fatal and non-fatal CVD events (24 and 20 years) and heart failure (20 years). The survival analysis was performed using Kaplan–Meier curves and Cox-proportional hazard models.Results “Heavy” OPA group subjects belonging to the “irregular” (less than 1–2 times 30 min exercise per week) LTPA group experienced the lowest overall mortality compared to other LTPA groups. Also, overall mortality was increased in the “mild” (p = 0.002) and CVD mortality in the” heavy” (p = 0.005) OPA group compared to “no activity”. The incidence of heart failure was increased in the “no exercise” LTPA compared to the “heavy regular” (p = 0.015) group.Conclusions Study subjects who were in physically demanding occupations (heavy OPA) seemed to benefit from less LTPA than WHO currently recommends. Thus we suggest targeting different LTPA recommendations to different OPA groups

Nighttime ambulatory pulse pressure predicts cardiovascular and all-cause mortality among middle-aged participants in the 21-year follow-up

Abstract Office pulse pressure (PP) is a predictor for cardiovascular (CV) events and mortality. Our aim was to evaluate ambulatory PP as a long-term risk factor in a random cohort of middle-aged participants. The Opera study took place in years 1991–1993, with a 24-h ambulatory blood pressure measurement (ABPM) performed to 900 participants. The end-points were non-fatal and fatal CV events, and deaths of all-causes. Follow-up period, until the first event or until the end of the year 2014, was 21.1 years (mean). Of 900 participants, 22.6% died (29.6% of men/15.6% of women, p&lt;.001). A CV event was experienced by 208 participants (23.1%), 68.3% of them were male (p&lt;.001). High nighttime ambulatory PP predicted independently CV mortality (hazard ratio [HR] 2.60; 95% confidence interval [CI 95%] 1.08–6.31, p=.034) and all-cause mortality in the whole population (HR 1.72; Cl 95% 1.06–2.78, p=.028). In males, both 24-h PP and nighttime PP associated with CV mortality and all-cause mortality (24-h PP HR for CV mortality 2.98; CI 95% 1.11–8.04, p=.031 and all-cause mortality HR 2.40; CI 95% 1.32–4.37, p=.004). Accordingly, nighttime PP; HR for CV mortality 3.13; CI 95% 1.14–8.56, p=.026, and for all-cause mortality HR 2.26; CI 95% 1.29–3.96, p=.004. Cox regression analyses were adjusted by sex, CV risk factors, and appropriate ambulatory mean systolic BP. In our study, high ambulatory nighttime PP was detected as a long-term risk factor for CV and all-cause mortality in middle-aged individuals

Higher hemoglobin levels are an independent risk factor for adverse metabolism and higher mortality in a 20-year follow-up

Abstract The aim of this study was to cross-sectionally and longitudinally examine whether higher hemoglobin (Hb) levels within the normal variation associate with key components of metabolic syndrome and total and cardiovascular mortality. The study included 967 Finnish subjects (age 40–59 years) followed for ≥ 20 years. The focus was on Hb levels, cardiovascular diseases (CVDs) and mortality rates. Higher Hb levels associated positively with key anthropometric and metabolic parameters at baseline. At the follow-up similar associations were seen in men. The highest Hb quartile showed higher leptin levels and lower adiponectin levels at baseline and follow-up (p &lt; 0.05) and lower plasma ghrelin levels at baseline (p &lt; 0.05). Higher baseline Hb levels associated independently with prevalence of type 2 diabetes at follow-up (p &lt; 0.01). The highest Hb quartile associated with higher serum alanine aminotransferase levels (p &lt; 0.001) and independently with increased risk for liver fat accumulation (OR 1.63 [1.03; 2.57]) at baseline. The highest Hb quartile showed increased risk for total (HR = 1.48 [1.01; 2.16]) and CVD-related mortality (HR = 2.08 [1.01; 4.29]). Higher Hb levels associated with an adverse metabolic profile, increased prevalence of key components of metabolic syndrome and higher risk for CVD-related and total mortality

Metabolic syndrome but not genetic polymorphisms known to induce NAFLD predicts increased total mortality in subjects with NAFLD (OPERA study)

Abstract Metabolic syndrome (MetS) and genetic polymorphisms PNPLA3 rs738409, TM6SF2 rs58542926 and MBOAT7 rs641738 are known inductors of non-alcoholic fatty liver disease (NAFLD). However, knowledge about how these affect the mortality of subjects with NAFLD is scarce. Therefore, we investigated the impact of MetS, PNPLA3 rs738409, TM6SF2 rs58542926 and MBOAT7 rs641738 on overall and cardiovascular disease (CVD) specific mortality among subjects with or without NAFLD. NAFLD diagnosis was based on liver ultrasound at the baseline. After this and other comprehensive examinations, 958 middle-aged Finns, 249 with NAFLD, were followed for 21 years. The mortality data was gathered from the National Death Registry. After multiple adjustments, the NAFLD individuals with MetS had increased risk of overall mortality as compared to the NAFLD subjects without MetS [2.054 (1.011–4.173, p = 0.046)]. However, PNPLA3 rs738409 [1.049 (0.650–1.692, p =0 .844)], TM6SF2 rs58542926 [0.721 (0.369–1.411, p = 0.340)] or MBOAT7 rs641738 [0.885 (0.543–1.439, p = 0.621)] did not affect the overall mortality. MetS was also a marker of increased risk of CVD mortality (15% vs. 2%, p =0.013) while genetic polymorphisms did not affect CVD mortality. In conclusion, MetS, but not the gene polymorphisms studied, predicts increased overall and CVD-specific mortality among NAFLD subjects