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1.
Curr Hypertens Rep ; 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38878251

ABSTRACT

PURPOSE OF REVIEW: This review summarizes current knowledge on blood pressure in children and adolescents (youth), with a focus on primary hypertension-the most common form of elevated blood pressure in this demographic. We examine its etiology, progression, and long-term cardiovascular implications. The review covers definitions and recommendations of blood pressure classifications, recent developments in measurement, epidemiological trends, findings from observational and clinical studies, and prevention and treatment, while identifying gaps in understanding and suggesting future research directions. RECENT FINDINGS: Youth hypertension is an escalating global issue, with regional and national variations in prevalence. While the principles of blood pressure measurement have remained largely consistent, challenges in this age group include a scarcity of automated devices that have passed independent validation for accuracy and a generally limited tolerance for ambulatory blood pressure monitoring. A multifaceted interplay of factors contributes to youth hypertension, impacting long-term cardiovascular health. Recent studies, including meta-analysis and sophisticated life-course modelling, reveal an adverse link between youth and life-course blood pressure and subclinical cardiovascular outcomes later in life. New evidence now provides the strongest evidence yet linking youth blood pressure with clinical cardiovascular events in adulthood. Some clinical trials have expanded our understanding of the safety and efficacy of antihypertensive medications in youth, but this remains an area that requires additional attention, particularly regarding varied screening approaches. This review outlines the potential role of preventing and managing blood pressure in youth to reduce future cardiovascular risk. A global perspective is necessary in formulating blood pressure definitions and strategies, considering the specific needs and circumstances in low- and middle-income countries compared to high-income countries.

2.
Lancet Microbe ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38909617

ABSTRACT

BACKGROUND: Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts. METHODS: In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18-70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25-74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5-7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards. FINDINGS: We profiled gut microbiota from 10 699 participants (4248 [39·7%] from the derivation cohort and 6451 [60·3%] from the validation cohort). 602 (5·6%) participants (152 [3·6%] from the derivation cohort; 450 [7·0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0·041; validation p=0·0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0·75 [95% CI 0·60-0·94] per 10% increase in butyrate producers, p=0·013; validation cohort 0·86 [0·77-0·96] per 10% increase, p=0·0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities. INTERPRETATION: Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections. FUNDING: Amsterdam UMC, Porticus, National Institutes of Health, Netherlands Organisation for Health Research and Development (ZonMw), and Leducq Foundation.

3.
J Thromb Haemost ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38782299

ABSTRACT

BACKGROUND: Increased risk of venous thromboembolism (VTE) is a life-threatening side effect for users of oral contraceptives (OCs) or hormone therapy (HT). OBJECTIVES: To investigate the potential for genetic predisposition to VTE in OC or HT users, we conducted a gene-by-environment case-only meta-analysis of genome-wide association studies (GWAS). METHODS: Use or nonuse of OCs (7 studies) or HT (8 studies) at the time of the VTE event was determined by pharmacy records or self-report. A synergy index (SI) was modeled for each variant in each study and submultiplicative/supramultiplicative gene-by-environment interactions were estimated. The SI parameters were first meta-analyzed across OC and HT studies and subsequently meta-analyzed to obtain an overall estimate. The primary analysis was agnostic GWAS and interrogated all imputed genotypes using a P value threshold of <5.0 × 10-8; secondary analyses were candidate-based. RESULTS: The VTE case-only OC meta-analysis included 2895 OC users and 6607 nonusers; the case-only HT meta-analysis included 2434 HT users and 12 793 nonusers. In primary GWAS meta-analyses, no variant reached genome-wide significance, but the smallest P value approached statistical significance: rs9386463 (P = 5.03 × 10-8). We tested associations for 138 candidate variants and identified 2 that exceeded statistical significance (0.05/138 = 3.62 × 10-4): F5 rs6025 (P = 1.87 × 10-5; SI, 1.29; previously observed) and F11 rs2036914 (P = 2.0 × 10-4; SI, 0.91; new observation). CONCLUSION: The candidate variant approach to identify submultiplictive/supramultiplicative associations between genetic variation and OC and HT use identified a new association with common genetic variation in F11, while the agnostic interrogations did not yield new discoveries.

4.
JAMA ; 331(22): 1898-1909, 2024 06 11.
Article in English | MEDLINE | ID: mdl-38739396

ABSTRACT

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. Results: The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.


Subject(s)
Biomarkers , Cardiovascular Diseases , Natriuretic Peptide, Brain , Peptide Fragments , Troponin I , Troponin T , Adult , Aged , Female , Humans , Male , Middle Aged , Atherosclerosis/blood , Biomarkers/blood , C-Reactive Protein/analysis , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Cohort Studies , Heart Failure/blood , Heart Failure/epidemiology , Heart Failure/mortality , Myocardial Infarction/epidemiology , Myocardial Infarction/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Predictive Value of Tests , Prognosis , Risk Factors , Troponin I/blood , Troponin T/blood , Internationality
5.
Eur J Nutr ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38753173

ABSTRACT

PURPOSE: Population-based studies on the associations of plant-based foods, red meat or dairy with gut microbiome are scarce. We examined whether the consumption of plant-based foods (vegetables, potatoes, fruits, cereals), red and processed meat (RPM) or dairy (fermented milk, cheese, other dairy products) are related to gut microbiome in Finnish adults. METHODS: We utilized data from the National FINRISK/FINDIET 2002 Study (n = 1273, aged 25-64 years, 55% women). Diet was assessed with 48-hour dietary recalls. Gut microbiome was analyzed using shallow shotgun sequencing. We applied multivariate analyses with linear models and permutational ANOVAs adjusted for relevant confounders. RESULTS: Fruit consumption was positively (beta = 0.03, SE = 0.01, P = 0.04), while a dairy subgroup including milk, cream and ice-creams was inversely associated (beta=-0.03, SE 0.01, P = 0.02) with intra-individual gut microbiome diversity (alpha-diversity). Plant-based foods (R2 = 0.001, P = 0.03) and dairy (R2 = 0.002, P = 0.01) but not RPM (R2 = 0.001, P = 0.38) contributed to the compositional differences in gut microbiome (beta-diversity). Plant-based foods were associated with several butyrate producers/cellulolytic species including Roseburia hominis. RPM associations included an inverse association with R. hominis. Dairy was positively associated with several lactic producing/probiotic species including Lactobacillus delbrueckii and potentially opportunistic pathogens including Citrobacter freundii. Dairy, fermented milk, vegetables, and cereals were associated with specific microbial functions. CONCLUSION: Our results suggest a potential association between plant-based foods and dairy or their subgroups with microbial diversity measures. Furthermore, our findings indicated that all the food groups were associated with distinct overall microbial community compositions. Plant-based food consumption particularly was associated with a larger number of putative beneficial species.

6.
Adv Sci (Weinh) ; 11(24): e2307718, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38647263

ABSTRACT

Results from two independent clinical validation studies for measuring hemodynamics at the patient's bedside using a compact finger probe are reported. Technology comprises a barometric pressure sensor, and in one implementation, additionally, an optical sensor for photoplethysmography (PPG) is developed, which can be used to measure blood pressure and analyze rhythm, including the continuous detection of atrial fibrillation. The capabilities of the technology are shown in several form factors, including a miniaturized version resembling a common pulse oximeter to which the technology could be integrated in. Several main results are presented: i) the miniature finger probe meets the accuracy requirements of non-invasive blood pressure instrument validation standard, ii) atrial fibrillation can be detected during the blood pressure measurement and in a continuous recording, iii) a unique comparison between optical and pressure sensing mechanisms is provided, which shows that the origin of both modalities can be explained using a pressure-volume model and that recordings are close to identical between the sensors. The benefits and limitations of both modalities in hemodynamic monitoring are further discussed.


Subject(s)
Photoplethysmography , Humans , Photoplethysmography/methods , Photoplethysmography/instrumentation , Equipment Design , Monitoring, Physiologic/methods , Monitoring, Physiologic/instrumentation , Hemodynamic Monitoring/methods , Hemodynamic Monitoring/instrumentation , Hemodynamics/physiology , Blood Pressure Determination/methods , Blood Pressure Determination/instrumentation , Point-of-Care Systems , Blood Pressure/physiology , Male , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Reproducibility of Results , Female
7.
Blood ; 143(23): 2425-2432, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38498041

ABSTRACT

ABSTRACT: The factor V Leiden (FVL; rs6025) and prothrombin G20210A (PTGM; rs1799963) polymorphisms are 2 of the most well-studied genetic risk factors for venous thromboembolism (VTE). However, double heterozygosity (DH) for FVL and PTGM remains poorly understood, with previous studies showing marked disagreement regarding thrombosis risk conferred by the DH genotype. Using multidimensional data from the UK Biobank (UKB) and FinnGen biorepositories, we evaluated the clinical impact of DH carrier status across 937 939 individuals. We found that 662 participants (0.07%) were DH carriers. After adjustment for age, sex, and ancestry, DH individuals experienced a markedly elevated risk of VTE compared with wild-type individuals (odds ratio [OR] = 5.24; 95% confidence interval [CI], 4.01-6.84; P = 4.8 × 10-34), which approximated the risk conferred by FVL homozygosity. A secondary analysis restricted to UKB participants (N = 445 144) found that effect size estimates for the DH genotype remained largely unchanged (OR = 4.53; 95% CI, 3.42-5.90; P < 1 × 10-16) after adjustment for commonly cited VTE risk factors, such as body mass index, blood type, and markers of inflammation. In contrast, the DH genotype was not associated with a significantly higher risk of any arterial thrombosis phenotype, including stroke, myocardial infarction, and peripheral artery disease. In summary, we leveraged population-scale genomic data sets to conduct, to our knowledge, the largest study to date on the DH genotype and were able to establish far more precise effect size estimates than previously possible. Our findings indicate that the DH genotype may occur as frequently as FVL homozygosity and may confer a similarly increased risk of VTE.


Subject(s)
Biological Specimen Banks , Factor V , Heterozygote , Prothrombin , Humans , Prothrombin/genetics , Factor V/genetics , Female , Male , Middle Aged , United Kingdom/epidemiology , Aged , Risk Factors , Venous Thromboembolism/genetics , Venous Thromboembolism/epidemiology , Adult , Thrombosis/genetics , Thrombosis/epidemiology , Thrombosis/etiology , Genetic Predisposition to Disease , Genotype , Polymorphism, Single Nucleotide , UK Biobank
8.
Nat Aging ; 4(4): 584-594, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38528230

ABSTRACT

Multiomics has shown promise in noninvasive risk profiling and early detection of various common diseases. In the present study, in a prospective population-based cohort with ~18 years of e-health record follow-up, we investigated the incremental and combined value of genomic and gut metagenomic risk assessment compared with conventional risk factors for predicting incident coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer disease and prostate cancer. We found that polygenic risk scores (PRSs) improved prediction over conventional risk factors for all diseases. Gut microbiome scores improved predictive capacity over baseline age for CAD, T2D and prostate cancer. Integrated risk models of PRSs, gut microbiome scores and conventional risk factors achieved the highest predictive performance for all diseases studied compared with models based on conventional risk factors alone. The present study demonstrates that integrated PRSs and gut metagenomic risk models improve the predictive value over conventional risk factors for common chronic diseases.


Subject(s)
Coronary Artery Disease , Diabetes Mellitus, Type 2 , Prostatic Neoplasms , Male , Humans , Diabetes Mellitus, Type 2/diagnosis , Prospective Studies , Risk Factors , Coronary Artery Disease/genetics , Genetic Risk Score
9.
Acta Obstet Gynecol Scand ; 103(6): 1132-1141, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38482868

ABSTRACT

INTRODUCTION: Female sexual dysfunction is very common, but its determinants remain under-investigated. Vasculogenic impairments are suggested to be related to female sexual dysfunction, but previous literature regarding the association is scarce. This study aims to study the association between arterial health and female sexual function in women in their 60s. MATERIAL AND METHODS: The sample for this cross-sectional study comprised 117 women (aged 60-64 years) who participated in the Finnish Retirement and Aging study. Arterial health was measured according to the participants' pulse wave velocity, ankle-brachial index, blood pressure, and pulse pressure. Sexual function was measured using the Female Sexual Function Index, which resulted in a total score and six sub-scores. Associations were examined using multivariable regression analyses, which were adjusted for age, relationship happiness, systemic menopausal hormone therapy and/or local estrogen, smoking, alcohol risk use, body mass index, and depressive symptoms. RESULTS: Higher diastolic blood pressure was associated with a higher total Female Sexual Function Index score (ß = 0.24, 95% confidence interval [CI] 0.07-0.41) and with higher desire (ß = 0.02, 95% CI 0.01-0.04), arousal (ß = 0.04, 95% CI 0.01-0.08), lubrication (ß = 0.04, 95% CI 0.002-0.08), satisfaction (ß = 0.03, 95% CI 0.003-0.05), and pain (ß = 0.06, 95% CI 0.02-0.10) sub-scores. Also, higher ankle-brachial index was associated with higher satisfaction sub-score (ß = 2.10, 95% CI 0.44-3.73) and lower pulse pressure was associated with higher orgasm sub-score (ß = 0.03, 95% CI 0.0002-0.06). Other associations between ankle-brachial index and Female Sexual Function Index scores were statistically insignificant, but considering the magnitude the findings may imply clinical significance. Systolic blood pressure and pulse wave velocity were not associated with sexual function. CONCLUSIONS: This study suggested a plausible association between higher diastolic blood pressure and female sexual function, but considering clinical significance our findings suggest an association between higher ankle-brachial index and good sexual function in women in their 60s.


Subject(s)
Ankle Brachial Index , Blood Pressure , Pulse Wave Analysis , Sexual Dysfunction, Physiological , Humans , Female , Middle Aged , Cross-Sectional Studies , Sexual Dysfunction, Physiological/epidemiology , Blood Pressure/physiology , Finland/epidemiology
10.
J Oral Microbiol ; 16(1): 2330867, 2024.
Article in English | MEDLINE | ID: mdl-38528961

ABSTRACT

Background: Gingivitis, i.e. inflammation of the gums, is often induced by dentalplaque. However, its exact link to the oral microbiota remains unclear. Methods: In a case-control study involving 120 participants, comprising 60 cases and 60 controls (mean age (SD) 36.6 (7.6) years; 50% males), nested within a prospective multicentre cohort study, we examined theoral microbiome composition of gingivitis patients and their controlsusing shotgun metagenomic sequencing of saliva samples. Participants underwent clinical and radiographic oral health examinations, including bleeding on probing (BOP), at six tooth sites. BOP ≥33%was considered 'generalized gingivitis/initial periodontitis'(GG/IP), and BOP <33% as 'healthy and localized gingivitis'(H/LG). Functional potential was inferred using HUMANn3. Results: GG/IP exhibited an increase in the abundance of Actinomyces, Porphyromonas, Aggregatibacter, Corynebacterium, Olsenella, and Treponema, whereas H/LG exhibited an increased abundance of Candidatus Nanosynbacter. Nineteen bacterial species and fourmicrobial functional profiles, including L-methionine, glycogen, andinosine-5'-phosphate biosynthesis, were associated with GG/IP. Constructing models with multiple markers resulted in a strong predictive value for GG/IP, with an area under the curve (ROC) of 0.907 (95% CI: 0.848-0.966). Conclusion: We observed distinct differences in the oral microbiome between the GG/IP and H/LG groups, indicating similar yet unique microbial profiles and emphasizing their potential role in progression of periodontal diseases.

11.
bioRxiv ; 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38328113

ABSTRACT

Pulmonary arterial hypertension (PAH) is a rare and fatal vascular disease with heterogeneous clinical manifestations. To date, molecular determinants underlying the development of PAH and related outcomes remain poorly understood. Herein, we identify pulmonary primary oxysterol and bile acid synthesis (PPOBAS) as a previously unrecognized pathway central to PAH pathophysiology. Mass spectrometry analysis of 2,756 individuals across five independent studies revealed 51 distinct circulating metabolites that predicted PAH-related mortality and were enriched within the PPOBAS pathway. Across independent single-center PAH studies, PPOBAS pathway metabolites were also associated with multiple cardiopulmonary measures of PAH-specific pathophysiology. Furthermore, PPOBAS metabolites were found to be increased in human and rodent PAH lung tissue and specifically produced by pulmonary endothelial cells, consistent with pulmonary origin. Finally, a poly-metabolite risk score comprising 13 PPOBAS molecules was found to not only predict PAH-related mortality but also outperform current clinical risk scores. This work identifies PPOBAS as specifically altered within PAH and establishes needed prognostic biomarkers for guiding therapy in PAH.

13.
Hypertension ; 81(5): 1065-1075, 2024 May.
Article in English | MEDLINE | ID: mdl-38390718

ABSTRACT

BACKGROUND: Wave separation analysis enables individualized evaluation of the aortic pulse wave components. Previous studies focused on the pressure height with overall positive but differing results. In the present analysis, we assessed the associations of the pressure of forward and backward (Pfor and Pref) pulse waves with prospective cardiovascular end points, with extended analysis for time to pressure peak (Tfor and Tref). METHODS: Participants in 3 IDCARS (International Database of Central Arterial Properties for Risk Stratification) cohorts (Argentina, Belgium, and Finland) aged ≥20 years with valid pulse wave analysis and follow-up data were included. Pulse wave analysis was done using the SphygmoCor device, and pulse wave separation was done using the triangular method. The primary end points consisted of cardiovascular mortality and nonfatal cardiovascular and cerebrovascular events. Multivariable-adjusted Cox regression was used to calculate hazard ratios. RESULTS: A total of 2206 participants (mean age, 57.0 years; 55.0% women) were analyzed. Mean±SDs for Pfor, Pref, Tfor, and Tfor/Tref were 31.0±9.1 mm Hg, 20.8±8.4 mm Hg, 130.8±35.5, and 0.51±0.11, respectively. Over a median follow-up of 4.4 years, 146 (6.6%) participants experienced a primary end point. Every 1 SD increment in Pfor, Tfor, and Tfor/Tref was associated with 27% (95% CI, 1.07-1.49), 25% (95% CI, 1.07-1.45), and 32% (95% CI, 1.12-1.56) higher risk, respectively. Adding Tfor and Tfor/Tref to existing risk models improved model prediction (∆Uno's C, 0.020; P<0.01). CONCLUSIONS: Pulse wave components were predictive of composite cardiovascular end points, with Tfor/Tref showing significant improvement in risk prediction. Pending further confirmation, the ratio of time to forward and backward pressure peak may be useful to evaluate increased afterload and signify increased cardiovascular risk.


Subject(s)
Cardiovascular Diseases , Vascular Stiffness , Humans , Female , Middle Aged , Male , Prospective Studies , Heart , Aorta , Heart Rate , Arteries , Pulse Wave Analysis , Blood Pressure , Risk Factors
14.
Article in English | MEDLINE | ID: mdl-38216540

ABSTRACT

Men and women have differing risks of adverse events after revascularization procedures and these differences could be partially driven by genetics. We studied the sex-specific differences in associations of polygenic risk scores (PRSs) with atrial fibrillation (AF), ischaemic stroke (STR), intracranial haemorrhage (ICH), myocardial infarction (MI) and gastrointestinal haemorrhage (GIH) in coronary revascularization patients. The study cohort comprised 5561 and 17 578 revascularized women and men. All participants underwent genotyping and register-based follow-up from 1961 to 2021. We calculated PRSs for all individuals and used Cox models with interaction term to examine the sex-specific associations between the PRSs and adverse outcomes after revascularization. The AF-PRS was more strongly associated with AF in men [hazard ratio (HR) per 1 standard deviation increase, 1.16; 95% confidence interval (CI), 1.12-1.19; P = 7.6 × 10-22) than in women (P for interaction 0.006). Conversely, ICH-PRS was more strongly associated with ICH after revascularization in women (HR, 1.32; 95% CI, 1.08-1.62; P = 0.008) than in men (P for interaction 0.008). We observed no sex-specific differences for the associations of PRSs with STR, MI or GIH. The genetic risk of AF after revascularization is greater in men than in women, and vice versa for ICH. Sex-specific PRSs could be used to identify individuals in high genetic risk for these complications.

15.
Arterioscler Thromb Vasc Biol ; 44(2): 477-487, 2024 02.
Article in English | MEDLINE | ID: mdl-37970720

ABSTRACT

BACKGROUND: Dyslipidemia is treated effectively with statins, but treatment has the potential to induce new-onset type-2 diabetes. Gut microbiota may contribute to this outcome variability. We assessed the associations of gut microbiota diversity and composition with statins. Bacterial associations with statin-associated new-onset type-2 diabetes (T2D) risk were also prospectively evaluated. METHODS: We examined shallow-shotgun-sequenced fecal samples from 5755 individuals in the FINRISK-2002 population cohort with a 17+-year-long register-based follow-up. Alpha-diversity was quantified using Shannon index and beta-diversity with Aitchison distance. Species-specific differential abundances were analyzed using general multivariate regression. Prospective associations were assessed with Cox regression. Applicable results were validated using gradient boosting. RESULTS: Statin use associated with differing taxonomic composition (R2, 0.02%; q=0.02) and 13 differentially abundant species in fully adjusted models (MaAsLin; q<0.05). The strongest positive association was with Clostridium sartagoforme (ß=0.37; SE=0.13; q=0.02) and the strongest negative association with Bacteroides cellulosilyticus (ß=-0.31; SE=0.11; q=0.02). Twenty-five microbial features had significant associations with incident T2D in statin users, of which only Bacteroides vulgatus (HR, 1.286 [1.136-1.457]; q=0.03) was consistent regardless of model adjustment. Finally, higher statin-associated T2D risk was seen with [Ruminococcus] torques (ΔHRstatins, +0.11; q=0.03), Blautia obeum (ΔHRstatins, +0.06; q=0.01), Blautia sp. KLE 1732 (ΔHRstatins, +0.05; q=0.01), and beta-diversity principal component 1 (ΔHRstatin, +0.07; q=0.03) but only when adjusting for demographic covariates. CONCLUSIONS: Statin users have compositionally differing microbiotas from nonusers. The human gut microbiota is associated with incident T2D risk in statin users and possibly has additive effects on statin-associated new-onset T2D risk.


Subject(s)
Diabetes Mellitus, Type 2 , Dyslipidemias , Gastrointestinal Microbiome , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Cross-Sectional Studies , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Dyslipidemias/diagnosis , Dyslipidemias/drug therapy , Dyslipidemias/epidemiology
16.
J Hypertens ; 42(2): 337-343, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37965725

ABSTRACT

OBJECTIVES: Stress, and particularly job strain, has been found to associate with ambulatory blood pressure (BP). Moreover, BP is known to vary between days. One potential over-looked factor underlying this day-to-day BP variation could be work-related psychosocial factors. Thus, we aimed to study the association between job strain, job demands, job control and day-to-day BP variation. METHODS: The home BP of 754 regularly working participants (mean age 50.9 ±â€Š4.8, women 51%) of the Finn-Home Study was measured twice in the morning and twice in the evening over seven days. Average SBP and DBP were calculated for each day. Work-related psychosocial factors were measured with survey. Multivariable-adjusted generalized linear models were used for statistical analysis. RESULTS: We found a greater SBP/DBP decrease between weekdays and weekend among participants with high job strain (-1.8 [95% confidence interval, 95% CI, -2.7 to -0.8]/-1.7 [95% CI, -2.3 to -1.1] mmHg) compared to participants with low job strain (-0.7 [95% CI, -1.1 to -0.2]/-0.7 [95% CI, -1.0 to -0.4] mmHg). The participants with high job demands showed a higher BP decrease between weekdays and weekend (-1.4 [95% CI, -2.0 to -0.8]/-1.3 [95% CI, -1.6 to -0.9] mmHg) than the participants with low job demands (-0.5 [95% CI, -1.1 to 0.0]/-0.6 [95% CI, -1.0 to -0.3] mmHg). We did not find BP differences regarding job control. CONCLUSION: High job strain and high job demands were associated with a greater BP reduction from weekdays to the weekend. Work-related psychosocial factors should be considered when assessing day-to-day BP variation.


Subject(s)
Hypertension , Occupational Stress , Humans , Female , Middle Aged , Blood Pressure/physiology , Blood Pressure Monitoring, Ambulatory , Research Design
17.
Eur J Prev Cardiol ; 31(5): 569-577, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-37976098

ABSTRACT

AIMS: The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period. METHODS AND RESULTS: The study sample comprised 553 818 individuals from 49 cohorts in 11 European countries (baseline: 1982-2012) who were followed up for a maximum of 10 years. Risk factors [sex, smoking, diabetes, non-HDL cholesterol, systolic blood pressure (BP), and body mass index (BMI)] and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor-outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. The differences in the risk factor-CVD associations between central Europe, northern Europe, southern Europe, and the UK were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (P = 0.043 for overall difference), and those with diabetes had a slightly lower HR in central Europe (P = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol [7% per mmol/L; 95% confidence interval (CI), 3-10%] and systolic BP (4% per 20 mmHg; 95% CI, 1-8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1-13%). CONCLUSION: The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk.


All classic cardiovascular disease (CVD) risk factors are still relevant in Europe, irrespective of regional area. The differences in the associations of CVD risk factors with overt CVD between regions of Europe are generally small. Minor temporal hazard decreases were observed for non-HDL cholesterol and systolic blood pressure, while a minor hazard increase was observed for body mass index.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Male , Humans , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Risk Factors , Cholesterol , Europe/epidemiology , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology
18.
J Intern Med ; 295(2): 196-205, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37899293

ABSTRACT

AIMS: Dementia is a major health problem. Cardiovascular diseases (CVD) and risk factors are associated with incident dementia. However, whether there is an association among CVD, Alzheimer's disease (AD) and vascular dementia (VD) at the population level remains unclear. METHODS: We analysed the association between CVD (heart failure [HF], atrial fibrillation [AF], myocardial infarction [MI], peripheral arterial disease, stroke and transient ischemic attack) and the incidence of dementia using nationwide FinnGen data of 218,192 individuals. The last follow-up information on dementia was available from October 2021. RESULTS: The age at the end of the follow-up was 61.7 ± 17.1 years, and 53% were women. Overall, we observed 9701 (4.4%) dementia, 6323 (2.9%) AD and 1918 (0.7%) VD cases. Individuals with CVD had a higher risk of developing dementia than unexposed individuals. In the multivariable-adjusted Cox models, stroke was most strongly associated with dementia (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.6-1.8). CVD was more strongly associated with VD than with AD. Individuals with HF and MI had an increased risk of AD (HF: HR 1.11, 95% CI 1.04-1.19; MI: HR 1.10, 95% CI 1.02-1.18). AF was associated with VD (HR 1.58, 95% CI 1.42-1.77), but not with AD (HR 1.03, 95% CI 0.97-1.09). Clinical characteristics, such as diabetes, smoking and alcohol abuse, were associated with both types of dementia. CONCLUSION: All major CVDs were associated with an increased risk of developing dementia, particularly VD. Therefore, CVD onset should prompt an assessment of cognitive decline and possible preventive measures.


Subject(s)
Alzheimer Disease , Atrial Fibrillation , Cardiovascular Diseases , Heart Failure , Myocardial Infarction , Stroke , Humans , Female , Male , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/complications , Risk Factors , Alzheimer Disease/epidemiology , Alzheimer Disease/complications , Myocardial Infarction/epidemiology , Myocardial Infarction/complications , Heart Failure/epidemiology , Stroke/epidemiology , Stroke/etiology , Atrial Fibrillation/complications
20.
iScience ; 26(11): 108295, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-38026187

ABSTRACT

Our aim is to develop a blood pressure (BP) measurement technology that could be integrated into a finger-worn pulse oximeter, eliminating the need for a brachial cuff. We present a miniature cuffless tonometric finger probe system that uses the oscillometric method to measure BP. Our approach uses a motorized press that is used to apply pressure to the fingertip to measure BP. We verified the functionality of the device in a clinical trial (n = 43) resulting in systolic and diastolic pressures ((mean ± SD) mmHg) of (-3.5 ± 8.4) mmHg and (-4.0 ± 4.4) mmHg, respectively. Comparison was made with manual auscultation (n = 26) and automated cuff oscillometry (n = 18). In addition to BP, we demonstrated the ability of the device to assess arterial stiffness (n = 18) and detect atrial fibrillation (n = 6). We were able to introduce a sufficiently small device that could be used for convenient ambulatory measurements with minimal discomfort.

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