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INTRODUCTION: Sex differences in blood pressure (BP), hypertension and hypertension mediated cardiovascular complications have become an increasingly important focus of attention. This narrative review gives an overview of current studies on this topic, with the aim to provide a deeper understanding of the sex-based disparities in hypertension with essential insights for refining prevention and management strategies for both men and women. METHODS AND RESULTS: We searched Medline, Embase and the Cochrane libray on sex differences in BP-trajectories and hypertension prevalence. In the past decade various population-based studies have revealed substantial sex-disparities in BP-trajectories throughout life with women having a larger increase in hypertension prevalence after 30 years of age and a stronger association between BP and cardiovascular disease (CVD). In general, the effects of antihypertensive treatment appear to be consistent across sexes in different populations, although there remains uncertainty about differences in the efficacy of BP lowering drugs below 55 years of age. CONCLUSION: The current uniform approach to the diagnosis and management of hypertension in both sexes neglects the distinctions in hypertension, while the differences underscore the need for sex-specific recommendations, particularly for younger individuals. A major limitation hampering insights into sex differences in BP-related outcomes is the lack of sex-stratified analyses or an adequate representation of women. Additional large-scale, longitudinal studies are imperative.
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Anti-Hipertensivos , Pressão Sanguínea , Hipertensão , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Feminino , Anti-Hipertensivos/uso terapêutico , Prevalência , Masculino , Pressão Sanguínea/efeitos dos fármacos , Fatores SexuaisRESUMO
BACKGROUND: The microbiota-derived short chain fatty acid butyrate has been shown to lower blood pressure (BP) in rodent studies. Nonetheless, the net effect of butyrate on hypertension in humans remains uncovered. In this study, for the first time, we aimed to determine the effect of oral butyrate on BP in patients with hypertension. METHODS: We performed a double-blind randomized placebo-controlled trial including 23 patients with hypertension. Antihypertensive medication was discontinued for the duration of the study with a washout period of 4 weeks before starting the intervention. Participants received daily oral capsules containing either sodium butyrate or placebo with an equivalent dosage of sodium chloride for 4 weeks. The primary outcome was daytime 24-hour systolic BP. Differences between groups over time were assessed using linear mixed models (group-by-time interaction). RESULTS: Study participants (59.0±3.7 years; 56.5% female) had an average baseline office systolic BP of 143.5±14.6 mmâ Hg and diastolic BP of 93.0±8.3 mmâ Hg. Daytime 24-hour systolic and diastolic BP significantly increased over the intervention period in the butyrate compared with the placebo group, with an increase of +9.63 (95% CI, 2.02-17.20) mmâ Hg in daytime 24-hour systolic BP and +5.08 (95% CI, 1.34-8.78) mmâ Hg in diastolic BP over 4 weeks. Butyrate levels significantly increased in plasma, but not in feces, upon butyrate intake, underscoring its absorption. CONCLUSIONS: Four-week treatment with oral butyrate increased daytime systolic and diastolic BP in subjects with hypertension. Our findings implicate that butyrate does not have beneficial effects on human hypertension, which warrants caution in future butyrate intervention studies. REGISTRATION: URL: https://clinicaltrialregister.nl/nl/trial/22936; Unique identifier: NL8924.
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OBJECTIVE: Midlife dyslipidemia is associated with higher risk of dementia in late-life dementia, but the impact of late-life dyslipidemia on dementia risk is uncertain. This may be due to the large heterogeneity in cholesterol measures and study designs employed. We used detailed data from a large prospective cohort of older persons to comprehensively assess the relation between a broad range of cholesterol measures and incident dementia, addressing potential biases, confounders, and modifiers. DESIGN: Post hoc observational analysis based on data from a dementia prevention trial (PreDIVA). SETTING AND PARTICIPANTS: 3392 community-dwelling individuals, without dementia, aged 70-78 years at baseline (recruited between June 2006 and March 2009). METHODS: Total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein A1 and B were assessed. Over a median of 6.7 years' follow-up, dementia was established by clinical diagnosis confirmed by independent outcome adjudication. Hazard ratios (HRs) for dementia and mortality were calculated using Cox regression. RESULTS: Dementia occurred in 231 (7%) participants. One-SD increase in LDL/HDL conveyed a 19% (P = .01) lower dementia risk and a 10% (P = .02) lower risk of dementia/mortality combined. This was independent of age, cardiovascular risk factors, cognitive function, apolipoprotein E genotype, and cholesterol-lowering drugs (CLD). This association was not influenced by the competing risk of mortality. Consistent and significant interactions suggested these associations were predominant in individuals with low body mass index (BMI) and higher education. CONCLUSIONS AND IMPLICATIONS: Dyslipidemia in older individuals was associated with a lower risk of dementia. Low BMI and higher education level mitigate poor outcomes associated with dyslipidemia. These findings suggest that a different approach may be appropriate for interpreting lipid profiles that are conventionally considered adverse in older adults. Such an approach may aid predicting dementia risk and designing intervention studies aimed at reducing dementia risk in older populations.
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Viruses are core components of the human microbiome, impacting health through interactions with gut bacteria and the immune system. Most human microbiome viruses are bacteriophages, which exclusively infect bacteria. Until recently, most gut virome studies focused on low taxonomic resolution (e.g., viral operational taxonomic units), hampering population-level analyses. We previously identified an expansive and widespread bacteriophage lineage in inhabitants of Amsterdam, the Netherlands. Here, we study their biodiversity and evolution in various human populations. Based on a phylogeny using sequences from six viral genome databases, we propose the Candidatus order Heliusvirales. We identify heliusviruses in 82% of 5441 individuals across 39 studies, and in nine metagenomes from humans that lived in Europe and North America between 1000 and 5000 years ago. We show that a large lineage started to diversify when Homo sapiens first appeared some 300,000 years ago. Ancient peoples and modern hunter-gatherers have distinct Ca. Heliusvirales populations with lower richness than modern urbanized people. Urbanized people suffering from type 1 and type 2 diabetes, as well as inflammatory bowel disease, have higher Ca. Heliusvirales richness than healthy controls. We thus conclude that these ancient core members of the human gut virome have thrived with increasingly westernized lifestyles.
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Bacteriófagos , Microbioma Gastrointestinal , Filogenia , Humanos , Bacteriófagos/genética , Bacteriófagos/isolamento & purificação , Bacteriófagos/classificação , Microbioma Gastrointestinal/genética , Genoma Viral/genética , Metagenoma/genética , Viroma/genética , Doenças Inflamatórias Intestinais/virologia , Biodiversidade , Diabetes Mellitus Tipo 2/virologia , Feminino , Masculino , Europa (Continente) , Países Baixos , AdultoRESUMO
Background: In cardiogenic shock (CS), contractile failure is often accompanied by a systemic inflammatory response syndrome. In contrast, many patients with septic shock (SS) develop cardiac dysfunction. A similar hemodynamic support strategy is often deployed in both syndromes but it is unclear whether this is justified based on profiles of biomarkers expressing neurohormonal activation and cardiovascular stress. Methods: In this prospective, multicenter cohort, 111 patients with acute myocardial infarction related CS were identified, and matched to patients with SS. Clinical parameters were collected and blood samples were obtained on day 1-3 of Intensive Care admission. Results: In this shock cohort comprising 222 patients, with a mean age of 61 (±13.5) years and of whom 161 (37 %) were male, we found that despite obvious clinical disparities on admission, mortality at 30-days did not differ (CS: 40.5 % vs. SS 43.1 %, p = 0.56). Overall, plasma concentrations of all biomarkers were higher in SS patients, with the largest difference on the first day. However, only in CS patients the biomarker concentrations were associated with mortality. Conclusion: In this prospective, multicenter cohort SS and CS patients showed similarities in baseline conditions and had similar mortality. However, several biomarkers only showed prognostic value in CS.
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Background: Remote monitoring devices for atrial fibrillation are known to positively contribute to the diagnostic process and therapy compliance. However, automatic algorithms within devices show varying sensitivity and specificity, so manual double-checking of electrocardiographic (ECG) recordings remains necessary. Objective: The purpose of this study was to investigate the validity of the KardiaMobile algorithm within the Dutch telemonitoring program (HartWacht). Methods: This retrospective study determined the diagnostic accuracy of the algorithm using assessments by a telemonitoring team as reference. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and F1 scores were determined. Results: A total of 2298 patients (59.5% female; median age 57 ± 15 years) recorded 86,816 ECGs between April 2019 and January 2021. The algorithm showed sensitivity of 0.956, specificity 0.985, PPV 0.996, NPV 0.847, and F1 score 0.976 for the detection of sinus rhythm. A total of 29 false-positive outcomes remained uncorrected within the same patients. The algorithm showed sensitivity of 0.989, specificity 0.953, PPV 0.835, NPV 0.997, and F1 score 0.906 for detection of atrial fibrillation. A total of 2 false-negative outcomes remained uncorrected. Conclusion: Our research showed high validity of the algorithm for the detection of both sinus rhythm and, to a lesser extent, atrial fibrillation. This finding suggests that the algorithm could function as a standalone instrument particularly for detection of sinus rhythm.
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Europe and North America are the 2 largest recipients of international migrants from low-resource regions in the world. Here, large differences in cardiovascular disease (CVD) morbidity and death exist between migrants and the host populations. This review discusses the CVD burden and its most important contributors among the largest migrant groups in Europe and North America as well as the consequences of migration to high-income countries on CVD diagnosis and therapy. The available evidence indicates that migrants in Europe and North America generally have a higher CVD risk compared with the host populations. Cardiometabolic, behavioral, and psychosocial factors are important contributors to their increased CVD risk. However, despite these common denominators, there are important ethnic differences in the propensity to develop CVD that relate to pre- and postmigration factors, such as socioeconomic status, cultural factors, lifestyle, psychosocial stress, access to health care and health care usage. Some of these pre- and postmigration environmental factors may interact with genetic (epigenetics) and microbial factors, which further influence their CVD risk. The limited number of prospective cohorts and clinical trials in migrant populations remains an important culprit for better understanding pathophysiological mechanism driving health differences and for developing ethnic-specific CVD risk prediction and care. Only by improved understanding of the complex interaction among human biology, migration-related factors, and sociocultural determinants of health influencing CVD risk will we be able to mitigate these differences and truly make inclusive personalized treatment possible.
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Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etnologia , América do Norte/epidemiologia , Europa (Continente)/epidemiologia , Migrantes/estatística & dados numéricos , Migrantes/psicologia , Fatores de Risco , Medição de Risco , Emigração e Imigração , Emigrantes e Imigrantes/estatística & dados numéricosRESUMO
Malignant hypertension (MHT) is a hypertensive emergency with excessive blood pressure (BP) elevation and accelerated disease progression. MHT is characterized by acute microvascular damage and autoregulation failure affecting the retina, brain, heart, kidney, and vascular tree. BP must be lowered within hours to mitigate patient risk. Both absolute BP levels and the pace of BP rise determine risk of target-organ damage. Nonadherence to the antihypertensive regimen remains the most common cause for MHT, although antiangiogenic and immunosuppressant therapy can also trigger hypertensive emergencies. Depending on the clinical presentation, parenteral or oral therapy can be used to initiate BP lowering. Evidence-based outcome data are spotty or lacking in MHT. With effective treatment, the prognosis for MHT has improved; however, patients remain at high risk of adverse cardiovascular and kidney outcomes. In this review, we summarize current viewpoints on the epidemiology, pathogenesis, and management of MHT; highlight research gaps; and propose strategies to improve outcomes.
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Hipertensão Maligna , Humanos , Hipertensão Maligna/epidemiologia , Hipertensão Maligna/fisiopatologia , Hipertensão Maligna/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologiaRESUMO
OBJECTIVE: We investigated ethnic health disparities in the Healthy Life in an Urban Setting multi-ethnic cohort using the multidimensional Healthy Ageing Score. STUDY DESIGN: We conducted a cross-sectional analysis of the study baseline data (2011-2015) collected through questionnaires/physical examinations for 17,091 participants (54.8 % women, mean (SD) age = 44.5 (12.8) years) from South-Asian Surinamese (14.8 %), African Surinamese (20.5 %), Dutch (24.3 %), Moroccan (15.5 %), Turkish (14.9 %), and Ghanaian (10.1 %) origins, living in Amsterdam, the Netherlands. MAIN OUTCOME MEASURES: We computed the Healthy Ageing Score developed in the Rotterdam Study, which has seven biopsychosocial domains: chronic diseases, mental health, cognitive function, physical function, pain, social support, and quality of life. That score was used to discern between healthy, moderate, and poor ageing. We explored differences in healthy ageing by ethnicity, sex, and age group using multinomial logistic regression. RESULTS: The Healthy Ageing Score [overall: poor (69.0 %), moderate (24.8 %), and healthy (6.2 %)] differed between ethnicities and was poorer in women and after midlife (cut-off 45 years) across ethnicities (all p < 0.001). In the fully adjusted models in men and women, poor ageing (vs. healthy ageing) was highest in the South-Asian Surinamese [adjusted odds ratios (95 % confidence intervals)] [2.96 (2.24-3.90) and 6.88 (3.29-14.40), respectively] and Turkish [2.80 (2.11-3.73) and 7.10 (3.31-15.24), respectively] vs. Dutch, in the oldest [5.89 (3.62-9.60) and 13.17 (1.77-98.01), respectively] vs. youngest, and in the divorced [1.48 (1.10-2.01) and 2.83 (1.39-5.77), respectively] vs. married. Poor ageing was inversely associated with educational and occupational levels, mainly in men. CONCLUSIONS: Compared with those of Dutch ethnic origin, ethnic minorities displayed less healthy ageing, which was more pronounced in women, before and after midlife, and was associated with sociodemographic factors.
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Etnicidade , Envelhecimento Saudável , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Crônica/etnologia , Cognição , Estudos Transversais , Etnicidade/estatística & dados numéricos , Envelhecimento Saudável/etnologia , Saúde Mental/etnologia , Países Baixos , Qualidade de Vida , Apoio Social , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Hypertension can be classified into different phenotypes according to systolic and diastolic blood pressure (BP). In younger adults, these phenotypical differences have different prognostic value for men and women. However, little is known about sex differences in the natural course of different BP phenotypes over time. METHODS: We used baseline and follow-up data from the multiethnic, population-based HELIUS study to assess differences in BP phenotypes over time in men and women agedâ<â45âyears stratified according to baseline office BP into normotension (<140/<90âmmHg), isolated systolic hypertension (ISH, ≥140/<90âmmHg), isolated diastolic hypertension (IDH, <140/≥90âmmHg) or systolic diastolic hypertension (SDH, ≥140/≥90âmmHg). Logistic regression adjusted for age, ethnicity, and follow-up time was used to assess the risk of hypertension at follow-up (BP ≥140/90âmmHg or use of antihypertensive medication), stratified by sex. RESULTS: We included 4103 participants [mean age 33.5âyears (SD 7.4), 43.4% men] with a median follow-up time of 6.2 years. Compared to normotensive individuals, the age-adjusted odds ratios (OR) for having hypertension at follow-up were 4.78 (95% CI 2.90; 7.76) for ISH, 6.02 (95% CI 3.70; 9.74) for IDH and 33.73 (95% CI 20.35; 58.38) for SDH in men, while in women, OR were 10.08 (95% CI 4.09; 25.56) for ISH, 27.59 (95% CI 14.68; 53.82) for IDH and 50.58 (95% CI 24.78; 114.84) for SDH. CONCLUSIONS: The risk of hypertension at follow-up was higher among women for all phenotypes compared to men, particularly in those with IDH. Findings of this study emphasize the importance of close BP monitoring in the young, especially in women.
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Pressão Sanguínea , Hipertensão , Fenótipo , Humanos , Feminino , Masculino , Adulto , Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Fatores Sexuais , Caracteres Sexuais , SeguimentosRESUMO
Background: Previous studies have reported gut microbiome alterations in Hashimoto's autoimmune thyroiditis (HT) patients. Yet, it is unknown whether an aberrant microbiome is present before clinical disease onset in participants susceptible to HT or whether it reflects the effects of the disease itself. In this study, we report for the first time a comprehensive characterization of the taxonomic and functional profiles of the gut microbiota in euthyroid seropositive and seronegative participants. Our primary goal was to determine taxonomic and functional signatures of the intestinal microbiota associated with serum thyroid peroxidase antibodies (TPOAb). A secondary aim was to determine whether different ethnicities warrant distinct reference intervals for accurate interpretation of serum thyroid biomarkers. Methods: In this cross-sectional study, euthyroid participants with (N = 159) and without (N = 1309) TPOAb were selected from the multiethnic (European Dutch, Moroccan, and Turkish) HEalthy Life In an Urban Setting (HELIUS) cohort. Fecal microbiota composition was profiled using 16S rRNA sequencing. Differences between the groups were analyzed based on the overall composition (alpha and beta diversity), as well as differential abundance (DA) of microbial taxa and functional pathways using multiple DA tools. Results: Overall composition showed a substantial overlap between the two groups (p > 0.05 for alpha-diversity; p = 0.39 for beta-diversity), indicating that TPOAb-seropositivity does not significantly differentiate gut microbiota composition and diversity. Interestingly, TPOAb status accounted for only a minor fraction (0.07%) of microbiome variance (p = 0.545). Further exploration of taxonomic differences identified 138 taxa nominally associated with TPOAb status. Among these, 13 taxa consistently demonstrated nominal significance across three additional DA methods, alongside notable associations within various functional pathways. Furthermore, we showed that ethnicity-specific reference intervals for serum thyroid biomarkers are not required, as no significant disparities in serum thyroid markers were found among the three ethnic groups residing in an iodine-replete area (p > 0.05 for thyrotropin, free thyroxine, and TPOAb). Conclusion: These findings suggest that there is no robust difference in gut microbiome between individuals with or without TPOAb in terms of alpha and beta-diversity. Nonetheless, several taxa were identified with nominal significance related to TPOAb presence. Further research is required to determine whether these changes indeed imply a higher risk of overt HT.
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Microbioma Gastrointestinal , Doença de Hashimoto , Humanos , Autoanticorpos , Biomarcadores , Estudos Transversais , Iodeto Peroxidase , RNA Ribossômico 16S/genética , SoroconversãoRESUMO
Introduction In the Netherlands, the prevalence of cardiovascular diseases (CVD) is higher among South-Asian Surinamese and lower among Moroccans compared to the Dutch. Traditional risk factors for atherosclerotic CVD do not fully explain these disparities. We aim to assess ethnic differences in plaque presence and intima media thickness (cIMT) and explore to which extent these differences are explained by traditional risk factors. Methods We used cross-sectional data from a subgroup of participants enrolled in the multi-ethnic population-based HEalthy Life In an Urban Setting (HELIUS) study who underwent carotid ultrasonography. Logistic and linear regression models were built to assess ethnic differences in plaque presence and cIMT with the Dutch population as reference. Additional models were created to adjust for socioeconomic status, body height and cardiovascular risk factors. Results Of the 3022 participants, 1183, 1051 and 790 individuals were of Dutch, South-Asian Surinamese and Moroccan descent. Mean age was 60.9 years (SD 8.0), 52.8% was female. Compared to the Dutch, we found lower odds for plaque presence in Moroccans (0.77, 95% CI 0.62; 0.95) and no significant differences between the South-Asian Surinamese and Dutch population (0.91, 95% CI 0.76; 1.10). After adjustment for CVD risk factors, we found a lower plaque presence in South-Asian Surinamese (0.63, 95% CI 0.48; 0.82). In both Moroccan and South-Asian Surinamese individuals, adjustment for socioeconomic status did not materially change the results. cIMT was lower in South-Asian Surinamese compared to the Dutch (-17.9 µm, 95% CI -27.9; -7.9) and partly explained by ethnic differences in body height as South-Asian Surinamese individuals were, on average, shorter than the Dutch population. No differences in cIMT between Moroccans and Dutch were found. Conclusions cIMT and plaque prevalence differ between ethnic groups independent of CVD risk. Lower plaque prevalence in Moroccans was partly attributable to a lower prevalence of traditional CVD risk factors, while body height was an important contributor to differences in cIMT in South-Asians. This study emphasizes the need for ethnic-specific cut-off values for plaque presence and cIMT.
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Background Medication nonadherence contributes to poor health outcomes but remains challenging to identify. This study assessed the association between self-rated adherence and systolic blood pressure, low-density lipoprotein cholesterol levels, cardiovascular events, and all-cause mortality in SPRINT (Systolic Blood Pressure Intervention Trial). Methods and Results A total of 9361 patients randomized to 2 systolic blood pressure target groups, <120 mm Hg (intensive) and <140 mm Hg (standard), self-rated their medication adherence at each visit by marking a scale, ranging from 0% to 100%. Lower and high adherence were defined as scores ≤80% and >80%, respectively. Linear mixed effect regression models and Cox proportional hazard models were used to evaluate the association between self-rated adherence and systolic blood pressure and low-density lipoprotein cholesterol and cardiovascular events and all-cause mortality, respectively. A total of 9278 participants (mean age 68±9.4 years, 35.6% female) had repeated self-rated adherence measurements available, with a mean of 15±4 measurements per participant over 3.8 years follow-up. Of these, 2694 participants (29.0%) had ≥1 adherence measurements ≤80%. Compared with high-adherent patients, patients with lower adherence had significantly higher estimated on-treatment systolic blood pressure at 2-year follow-up: 128.7 (95% CI, 127.6-129.9) versus 120.0 (95% CI, 119.7-120.2) mm Hg in the intensive arm; and 139.8 (95% CI 138.4-141.1) versus 135.0 (95% CI 134.7-135.2) in the standard arm. Moreover, lower adherence was associated with an estimated 11 mg/dL higher low-density lipoprotein cholesterol level, more cardiovascular events (hazard ratio [HR], 1.69 [95% CI, 1.20-2.39]), and higher all-cause mortality (HR, 1.63 [95% CI, 1.16-2.31]). Conclusions Self-rated adherence allows identification of lower medication adherence and correlates with blood pressure control, low-density lipoprotein cholesterol levels, and adverse outcomes.
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OBJECTIVE: Evidence shows that the conventional cardiometabolic risk factors do not fully explain the burden of microvascular complications in type 2 diabetes (T2D). One potential factor is the impact of pulmonary dysfunction on systemic microvascular injury. We assessed the associations between spirometric impairments and systemic microvascular complications in T2D. DESIGN: Cross-sectional study. SETTING: National Diabetes Management and Research Centre in Ghana. PARTICIPANTS: The study included 464 Ghanaians aged ≥35 years with established diagnosis of T2D without primary myocardial disease or previous/current heart failure. Participants were excluded if they had primary lung disease including asthma or chronic obstructive pulmonary disease. PRIMARY AND SECONDARY OUTCOME MEASURES: The associations of spirometric measures (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio) with microvascular complications (nephropathy (albumin-creatinine ratio ≥3 mg/g), neuropathy (vibration perception threshold ≥25 V and/or Diabetic Neuropathy Symptom score >1) and retinopathy (based on retinal photography)) were assessed using multivariable logistic regression models with adjustments for age, sex, diabetes duration, glycated haemoglobin concentration, suboptimal blood pressure control, smoking pack years and body mass index. RESULTS: In age and sex-adjusted models, lower Z-score FEV1 was associated with higher odds of nephropathy (OR 1.55, 95% CI 1.19-2.02, p=0.001) and neuropathy (1.27 (1.01-1.65), 0.038) but not retinopathy (1.22 (0.87-1.70), 0.246). Similar observations were made for the associations of lower Z-score FVC with nephropathy (1.54 (1.19-2.01), 0.001), neuropathy (1.25 (1.01-1.54), 0.037) and retinopathy (1.19 (0.85-1.68), 0.318). In the fully adjusted model, the associations remained significant for only lower Z-score FEV1 with nephropathy (1.43 (1.09-1.87), 0.011) and neuropathy (1.34 (1.04-1.73), 0.024) and for lower Z-score FVC with nephropathy (1.45 (1.11-1.91), 0.007) and neuropathy (1.32 (1.03-1.69), 0.029). Lower Z-score FEV1/FVC ratio was not significantly associated with microvascular complications in age and sex and fully adjusted models. CONCLUSION: Our study shows positive but varying strengths of associations between pulmonary dysfunction and microvascular complications in different circulations. Future studies could explore the mechanisms linking pulmonary dysfunction to microvascular complications in T2D.
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Diabetes Mellitus Tipo 2 , Doenças Retinianas , Humanos , Estudos Transversais , Gana , PulmãoRESUMO
Blood pressure (BP) responses to sodium intake show great variation, discriminating salt-sensitive (SS) from salt-resistant (SR) individuals. The pathophysiology behind salt sensitivity is still not fully elucidated. We aimed to investigate salt-induced effects on body fluid, vascular tone, and autonomic cardiac response with regard to BP change in healthy normotensive individuals. We performed a randomized crossover study in 51 normotensive individuals with normal body mass index and estimated glomerular filtration rate. Subjects followed both a low-Na+ diet (LSD, <50 mmol/day) and a high-Na+ diet (HSD, >200 mmol/day). Cardiac output, systemic vascular resistance (SVR), and cardiac autonomous activity, through heart rate variability and cross-correlation baroreflex sensitivity (xBRS), were assessed with noninvasive continuous finger BP measurements. In a subset, extracellular volume (ECV) was assessed by iohexol measurements. Subjects were characterized as SS if mean arterial pressure (MAP) increased ≥3 mmHg after HSD. After HSD, SS subjects (25%) showed a 6.1-mmHg (SD 1.9) increase in MAP. No differences between SS and SR in body weight, cardiac output, or ECV were found. SVR was positively correlated with Delta BP (r = 0.31, P = 0.03). xBRS and heart rate variability were significantly higher in SS participants compared to SR participants after both HSD and LSD. Sodium loading did not alter heart rate variability within groups. Salt sensitivity in normotensive individuals is associated with an inability to decrease SVR upon high salt intake that is accompanied by alterations in autonomous cardiac regulation, as reflected by decreased xBRS and heart rate variability. No discriminatory changes upon high salt were observed among salt-sensitive individuals in body weight and ECV.NEW & NOTEWORTHY Extracellular fluid expansion in normotensive individuals after salt loading is present in both salt-sensitive and salt-resistant individuals and is not discriminatory to the blood pressure response to sodium loading in a steady-state measurement. In normotensive subjects, the ability to sufficiently vasodilate seems to play a pivotal role in salt sensitivity. In a normotensive cohort, differences in sympathovagal balance are also present in low-salt conditions rather than being affected by salt loading. Whereas treatment and prevention of salt-sensitive blood pressure increase are mostly focused on renal sodium handling and extracellular volume regulation, our study suggests that an inability to adequately vasodilate and altered autonomous cardiac functioning are additional key players in the pathophysiology of salt-sensitive blood pressure increase.
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Hipertensão , Cloreto de Sódio na Dieta , Humanos , Pressão Sanguínea , Cloreto de Sódio na Dieta/efeitos adversos , Frequência Cardíaca/fisiologia , Estudos Cross-Over , Cloreto de Sódio/farmacologia , Sódio/farmacologia , Peso CorporalRESUMO
Renal sympathetic innervation is important in the control of renal and systemic hemodynamics and is a target for pharmacological and catheter-based therapies. The effect of a physiological sympathetic stimulus using static handgrip exercise on renal hemodynamics and intraglomerular pressure in humans is unknown. We recorded renal arterial pressure and flow velocity in patients with a clinical indication for coronary or peripheral angiography using a sensor-equipped guidewire during baseline, handgrip, rest, and hyperemia following intrarenal dopamine (30 µg/kg). Changes in perfusion pressure were expressed as the change in mean arterial pressure, and changes in flow were expressed as a percentage with respect to baseline. Intraglomerular pressure was estimated using a Windkessel model. A total of 18 patients (61% male and 39% female) with a median age of 57 yr (range: 27-85 yr) with successful measurements were included. During static handgrip, renal arterial pressure increased by 15.2 mmHg (range: 4.2-53.0 mmHg), whereas flow decreased by 11.2%, but with a large variation between individuals (range: -13.4 to 49.8). Intraglomerular pressure increased by 4.2 mmHg (range: -3.9 to 22.1 mmHg). Flow velocity under resting conditions remained stable, with a median of 100.6% (range: 82.3%-114.6%) compared with baseline. During hyperemia, maximal flow was 180% (range: 111%-281%), whereas intraglomerular pressure decreased by 9.6 mmHg (interquartile range: 4.8 to 13.9 mmHg). Changes in renal pressure and flow during handgrip exercise were significantly correlated (ρ = -0.68, P = 0.002). Measurement of renal arterial pressure and flow velocity during handgrip exercise allows the identification of patients with higher and lower sympathetic control of renal perfusion. This suggests that hemodynamic measurements may be useful to assess the response to therapeutic interventions aimed at altering renal sympathetic control.NEW & NOTEWORTHY Renal sympathetic innervation is important in the homeostasis of systemic and renal hemodynamics. We showed that renal arterial pressure significantly increased and that flow decreased during static handgrip exercise using direct renal arterial pressure and flow measurements in humans, but with a large difference between individuals. These findings may be useful for future studies aimed to assess the effect of interventions that influence renal sympathetic control.
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Força da Mão , Hiperemia , Humanos , Masculino , Feminino , Força da Mão/fisiologia , Hemodinâmica/fisiologia , Rim , Pressão Arterial , Pressão Sanguínea/fisiologia , Sistema Nervoso SimpáticoRESUMO
BACKGROUND AND AIMS: Since plasma metabolites can modulate blood pressure (BP) and vary between men and women, we examined sex differences in plasma metabolite profiles associated with BP and sympathicovagal balance. Our secondary aim was to investigate associations between gut microbiota composition and plasma metabolites predictive of BP and heart rate variability (HRV). METHODS: From the HELIUS cohort, we included 196 women and 173 men. Office systolic BP and diastolic BP were recorded, and heart rate variability (HRV) and baroreceptor sensitivity (BRS) were calculated using finger photoplethysmography. Plasma metabolomics was measured using untargeted LC-MS/MS. Gut microbiota composition was determined using 16S sequencing. We used machine learning models to predict BP and HRV from metabolite profiles, and to predict metabolite levels from gut microbiota composition. RESULTS: In women, best predicting metabolites for systolic BP included dihomo-lineoylcarnitine, 4-hydroxyphenylacetateglutamine and vanillactate. In men, top predictors included sphingomyelins, N-formylmethionine and conjugated bile acids. Best predictors for HRV in men included phenylacetate and gentisate, which were associated with lower HRV in men but not in women. Several of these metabolites were associated with gut microbiota composition, including phenylacetate, multiple sphingomyelins and gentisate. CONCLUSIONS: Plasma metabolite profiles are associated with BP in a sex-specific manner. Catecholamine derivatives were more important predictors for BP in women, while sphingomyelins were more important in men. Several metabolites were associated with gut microbiota composition, providing potential targets for intervention.
Assuntos
Caracteres Sexuais , Esfingomielinas , Humanos , Masculino , Feminino , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Cromatografia Líquida , Gentisatos , Espectrometria de Massas em Tandem , FenilacetatosRESUMO
BACKGROUND: During the course of history, various important lifestyle changes have caused profound transitions of the gut microbiome. These include the introduction of agriculture and animal husbandry, a shift from a nomadic to a more sedentary lifestyle, and recently increased levels of urbanization and a transition towards a more Western lifestyle. The latter is linked with shifts in the gut microbiome that have a reduced fermentative capability and which are commonly associated with diseases of affluence. In this study, in which 5193 subjects are included, we investigated the direction of microbiome shifts that occur in various ethnicities living in Amsterdam by comparing 1st and 2nd generation participants. We furthermore validated part of these findings with a cohort of subjects that moved from rural Thailand to the USA. RESULTS: The abundance of the Prevotella cluster, which includes P. copri and the P. stercorea trophic network, diminished in the 2nd generation Moroccans and Turks but also in younger Dutch, whilst the Western-associated Bacteroides/Blautia/Bifidobacterium (BBB) cluster, which has an inverse correlation with α-diversity, increased. At the same time, the Christensenellaceae/Methanobrevibacter/Oscillibacter trophic network, which is positively associated with α-diversity and a healthy BMI, decreased in younger Turks and Dutch. Large compositional shifts were not observed in South-Asian and African Surinamese, in whom the BBB cluster is already dominant in the 1st generation, but ASV-level shifts towards certain species, associated amongst others with obesity, were observed. CONCLUSION: The Moroccan and Turkish populations, but also the Dutch population are transitioning towards a less complex and fermentative less capable configuration of the gut microbiota, which includes a higher abundance of the Western-associated BBB cluster. The Surinamese, whom have the highest prevalence of diabetes and other diseases of affluence, are already dominated by the BBB cluster. Given the continuous increase in diseases of affluence, this devolution towards low-diversity and fermentatively less capable gut microbiome compositions in urban environments is a worrying development. Video Abstract.