Diastolic dysfunction of the left ventricle (LVDD) is equally common in elderly women and men. LVDD is a condition that can remain latent for a long time but is also held responsible for elevated ...left ventricular filling pressures and high pulmonary pressures that may result in (exercise-induced) shortness of breath. This symptom is the hallmark of heart failure with preserved ejection fraction (HFpEF) which is predominantly found in women as compared to men within the HF spectrum. Given the mechanistic role of LVDD in the development of HFpEF, we review risk factors and mechanisms that may be responsible for this sex-specific progression of LVDD towards HFpEF from an epidemiological point-of-view and propose future research directions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although the association between menopause and cardiovascular disease (CVD) risk has been studied extensively, the simultaneous role of chronological aging herein remains underexposed. This study ...aims to disentangle the relationships of menopausal status and chronological aging with CVD risk factors in the largest study population to date.
In this cross-sectional study, CVD risk factors were compared between women with a different menopausal status within the same yearly age strata. The study population comprised female participants of the baseline visit of the population-based LifeLines Cohort Study. A total of 63,466 women, aged between 18 and 65 years, was included. Of them, 39,379 women were considered to be premenopausal, 8669 were perimenopausal, 14,514 were naturally postmenopausal, and 904 were surgically postmenopausal.
Compared to postmenopausal women aged 45 years, average total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) were 0.5 and 0.4 mmol/L higher, respectively, in postmenopausal women aged 50. Systolic and diastolic blood pressure levels were 4 and 1 mmHg higher, respectively. At all ages between 46 and 55 years, and after adjustment for confounders, naturally postmenopausal women had 0.2 to 0.4 mmol/L higher TC and 0.1 to 0.3 mmol/L higher LDL-c levels compared to premenopausal women in the same age range. Systolic blood pressure levels were up to 4 mmHg lower in naturally post- compared to premenopausal women at all ages between 29 and 52 years. Body mass index levels were up to 3.2 kg/m
higher in women with surgical menopause compared to all other women between the ages 32 and 52 years. All aforementioned results were statistically significant.
Chronological age and menopausal status are both independently associated with CVD risk factors. Based on the comparatively smaller observed differences associated with menopausal status than with chronological aging, the significance of a more unfavorable lipid profile in a later reproductive stage may be less obvious than previously thought.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Aim of the study A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as ...‘epigenetic clock’, has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. Methods Here, we profiled DNA methylation changes in a nested case–control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. Results We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007–1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007–1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020–1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03–1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. Conclusion Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility.
Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a ...stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium.
The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2).
No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios HRs, 1.06-1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04-1.23).
Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. PREREGISTRATION NUMBER: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.
Coronary microvascular dysfunction (CMD) is an important underlying cause of angina pectoris. Currently, no diagnostic tool is available to directly visualize the coronary microvasculature. Invasive ...microvascular reactivity testing is the diagnostic standard for CMD, but several non-invasive imaging techniques are being evaluated. However, evidence on reported non-invasive parameters and cut-off values is limited. Thus, we aimed to provide an overview of reported non-invasive parameters and corresponding cut-off values for CMD.
Pubmed and EMBASE databases were systematically searched for studies enrolling patients with angina pectoris without obstructed coronary arteries, investigating at least one non-invasive imaging technique to quantify CMD. Methodological quality assessment of included studies was performed using QUADAS-2.
Thirty-seven studies were included. Ten cardiac magnetic resonance studies reported MPRI and nine positron emission tomography (PET) and transthoracic echocardiography (TTE) studies reported CFR. Mean MPRI ranged from 1.47 ± 0.36 to 2.01 ± 0.41 in patients and from 1.50 ± 0.47 to 2.68 ± 0.49 in controls without CMD. Reported mean CFR in PET and TTE ranged from 1.39 ± 0.31 to 2.85 ± 1.35 and 1.69 ± 0.40 to 2.40 ± 0.40 for patients, and 2.68 ± 0.83 to 4.32 ± 1.78 and 2.65 ± 0.65 to 3.31 ± 1.10 for controls, respectively.
This systematic review summarized current evidence on reported parameters and cut-off values to diagnose CMD for various non-invasive imaging modalities. In current clinical practice, CMD is generally diagnosed with a CFR less than 2.0. However, due to heterogeneity in methodology and reporting of outcome measures, outcomes could not be compared and no definite reference values could be provided.
Angina without angiographic evidence of obstructive coronary artery disease (ANOCA) is a highly prevalent condition with insufficient pathophysiological knowledge and lack of evidence-based medical ...therapies. This affects ANOCA patients prognosis, their healthcare utilization and quality of life. In current guidelines, performing a coronary function test (CFT) is recommended to identify a specific vasomotor dysfunction endotype. The NetherLands registry of invasive Coronary vasomotor Function testing (NL-CFT) has been designed to collect data on ANOCA patients undergoing CFT in the Netherlands.
The NL-CFT is a web-based, prospective, observational registry including all consecutive ANOCA patients undergoing clinically indicated CFT in participating centers throughout the Netherlands. Data on medical history, procedural data and (patient reported) outcomes are gathered.
The implementation of a common CFT protocol in all participating hospitals promotes an equal diagnostic strategy and ensures representation of the entire ANOCA population. A CFT is performed after ruling out obstructive coronary artery disease. It comprises of both acetylcholine vasoreactivity testing as well as bolus thermodilution assessment of microvascular function. Optionally, continuous thermodilution or Doppler flow measurements can be performed. Participating centers can perform research using own data, or pooled data will be made available upon specific request via a secure digital research environment, after approval of a steering committee.
NL-CFT will be an important registry by enabling both observational and registry based (randomized) clinical trials in ANOCA patients undergoing CFT.
•NL-CFT is a web-based, prospective, observational registry.•All consecutive ANOCA patients undergoing clinically indicated CFT are included.•NL-CFT enables both observational and registry based (randomized) clinical trials.
The causal effects of alcohol-in-moderation on cardiometabolic health are continuously debated. Mendelian randomization (MR) is an established method to address causal questions in observational ...studies. We performed a systematic review of the current evidence from MR studies on the association between alcohol consumption and cardiometabolic diseases, all-cause mortality and cardiovascular risk factors. We performed a systematic search of the literature, including search terms on type of design and exposure. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. We additionally looked at exploration of non-linearity. We reported the direction of the studied associations. Our search yielded 24 studies that were eligible for inclusion. A full instrumental variable analysis was performed in 17 studies (71%) and 13 out of 24 studies (54%) validated all three key assumptions. Five studies (21%) assessed potential non-linearity. In general, null associations were reported for genetically predicted alcohol consumption with the primary outcomes cardiovascular disease (67%) and diabetes (75%), while the only study on all-cause mortality reported a detrimental association. Considering the heterogeneity in methodological quality of the included MR studies, it is not yet possible to draw conclusions on the causal role of moderate alcohol consumption on cardiometabolic health. As MR is a rapidly evolving field, we expect that future MR studies, especially with recent developments regarding instrument selection and non-linearity methodology, will further substantiate this discussion.
•Previous studies found contradictory results of the association between vasomotor menopausal symptoms and cardiovascular outcomes.•We found no convincing association between vasomotor menopausal ...symptoms or the duration of symptoms and cardiovascular outcomes.•This is de largest study to date of the association of vasomotor menopausal symptoms and cardiovascular outcomes.•This is the only study to have investigated the duration of menopausal symptoms in relation to cardiovascular outcomes.
To ascertain the association between vasomotor menopausal symptoms (VSM), hot flushes and night sweats, and cardiovascular disease, coronary heart disease and cerebrovascular disease.
The study sample comprised 8881 women (aged 45–50 years) with available hospital separation data from the 1946-51 cohort (1996–2016) of the ongoing Australian Longitudinal Study on Women’s Health, a national prospective cohort study.
First fatal or non-fatal cardiovascular disease, coronary heart disease, and cerebrovascular disease events were obtained through linkage with hospital admission data, the National Death Index, and Medicare Benefits Schedule. Hot flushes and night sweats were assessed via questionnaires at each main survey. Additionally, we calculated the duration of symptoms based on whether or not women reported vasomotor menopausal symptoms in each survey.
There were 925 cardiovascular disease, 484 coronary heart disease and 154 cerebrovascular disease events. There was no consistent evidence of any association with vasomotor menopausal symptoms, hot flushes and night sweats. We did find marginally statistically significant associations between presence of night sweats and cardiovascular disease (Hazard Ratio = 1.18, 95 % Confidence Interval: 1.01–1.38), and between the duration of vasomotor menopausal symptoms years and coronary heart disease (Hazard Ratioper year = 1.03, 95 % Confidence Interval: 1.00–1.05). However, given the number of associations tested, these findings could very well have arisen by chance.
In this large longitudinal study with 20 years of follow-up and clinical outcomes we did not find a convincing association between vasomotor menopausal symptoms, hot flushes, night sweats and cardiovascular disease, coronary heart disease and cerebrovascular disease.
BACKGROUND Timing of natural menopause has great implications for fertility and women's health. Age at natural menopause (ANM) is largely influenced by genetic factors. In the past decade, several ...genetic studies have been conducted to identify genes in ANM, which can help us unravel the biological pathways underlying this trait and the associated infertility and health risks. After providing an overview of the results of the genetic studies performed so far, we give recommendations for future studies in identifying genetic factors involved in determining the variation in timing of natural menopause. METHODS The electronic databases of Pubmed and Embase were systematically searched until September 2009 for genetic studies on ANM, using relevant keywords on the subject. Additional papers identified through hand search were also included. RESULTS Twenty-eight papers emerged from our literature search. A number of genetic regions and variants involved in several possible pathways underlying timing of ANM were identified, including two possible interesting regions (9q21.3 and chromosome 8 at 26 cM) in linkage analyses. Recent genome-wide association studies have identified two genomic regions (19q13.42 and 20p12.3), containing two promising candidate genes (BRKS1 and MCM). In the candidate gene association studies on ANM, very few consistent associations were found. CONCLUSION A number of genetic variants have been discovered in association with ANM, although the overall results have been rather disappointing. We have described possible new strategies for future genetic studies to identify more genetic loci involved in the variation in menopausal age.
Abstract Background and aims Studies comparing dietary patterns derived from different a posteriori methods in view of predicting disease risk are scarce. We aimed to explore differences between ...dietary patterns derived from principal component- (PCA) and k-means cluster analysis (KCA) in relation to their food group composition and ability to predict CHD and stroke risk. Methods and results The study was conducted in the EPIC-NL cohort that consists of 40,011 men and women. Baseline dietary intake was measured using a validated food-frequency questionnaire. Food items were consolidated into 31 food groups. Occurrence of CHD and stroke was assessed through linkage with registries. After 13 years of follow-up, 1,843 CHD and 588 stroke cases were documented. Both PCA and KCA extracted a prudent pattern (high intakes of fish, high-fiber products, raw vegetables, wine) and a western pattern (high consumption of French fries, fast food, low-fiber products, other alcoholic drinks, soft drinks with sugar) with small variation between components and clusters. The prudent component was associated with a reduced risk of CHD (HR for extreme quartiles: 0.87; 95%-CI: 0.75–1.00) and stroke (0.68; 0.53–0.88). The western component was not related to any outcome. The prudent cluster was related with a lower risk of CHD (0.91; 0.82–1.00) and stroke (0.79; 0.67–0.94) compared to the western cluster. Conclusion PCA and KCA found similar underlying patterns with comparable associations with CHD and stroke risk. A prudent pattern reduced the risk of CHD and stroke.
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