Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies.

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.

Can eHealth programs for cardiac arrhythmias be scaled-up by using the KardiaMobile algorithm?

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.

Developing practical recommendations for drug-disease interactions in patients with hypertension.

Background: Hypertension, a significant risk factor for cardiovascular diseases, demands proactive management as cardiovascular diseases remain the leading cause of death worldwide. Reducing systolic and diastolic blood pressure levels below recommended reference values of <140/90 mmHg can lead to a significant reduction of the risk of CVD and all-cause mortality. However, treatment of hypertension can be difficult and the presence of comorbidities could further complicate this treatment. Drugs used to manage these comorbidities may inadvertently have an impact on blood pressure, resulting in a phenomenon known as drug-disease interaction. This study aims to assess the safety of medication that can affect blood pressure in patients with hypertension and provide practical recommendations for healthcare professionals. Methods: For the development of recommendations for the drug-disease interaction (DDSI) hypertension, a six-step plan that combined literature selection and multidisciplinary expert opinion was used. The process involved (1) defining the scope of the DDSI and selecting relevant drugs, (2) collecting evidence, (3) data-extraction, (4) reaching of expert consensus, (5) publication and implementation of the recommendations in healthcare systems and (6) updating the information. Results: An increase of 10 mmHg in systolic blood pressure and 5 mmHg in diastolic blood pressure was defined as clinically relevant. Corticosteroids, danazol, and yohimbine caused a clinically relevant DDSI with hypertension. Several other drugs with warnings for hypertension in the official product information were assessed to have no clinically relevant DDSI due to minor influence or lack of data on blood pressure. Drugs with evidence for a relevant change in blood pressure which are prescribed under close monitoring of blood pressure according to clinical guidelines, were deemed to be not clinically relevant for signalling. Conclusion: This study provides specific recommendations that can be implemented directly in clinical practice, for example, in clinical decision support systems, potentially resulting in safer drug use in patients with hypertension and better healthcare by reducing alert fatigue. Future research should focus on evaluating the effectiveness of implementation strategies and their impact on reducing unsafe use of medication in patients with hypertension.

Biomarker patterns in patients with cardiogenic shock versus septic shock.

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.

Malignant Hypertension:A Systemic Cardiovascular Disease: JACC Review Topic of the Week.

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.

International Migration and Cardiovascular Health: Unraveling the Disease Burden Among Migrants to North America and Europe.

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.

Ethnic variations in metabolic syndrome components and their associations with the gut microbiota: the HELIUS study.

BACKGROUND: The occurrence of metabolic syndrome (MetS) and the gut microbiota composition are known to differ across ethnicities yet how these three factors are interwoven is unknown. Also, it is unknown what the relative contribution of the gut microbiota composition is to each MetS component and whether this differs between ethnicities. We therefore determined the occurrence of MetS and its components in the multi-ethnic HELIUS cohort and tested the overall and ethnic-specific associations with the gut microbiota composition. METHODS: We included 16,209 treatment naïve participants of the HELIUS study, which were of Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish, and Moroccan descent to analyze MetS and its components across ethnicities. In a subset (n = 3443), the gut microbiota composition (16S) was associated with MetS outcomes using linear and logistic regression models. RESULTS: A differential, often sex-dependent, prevalence of MetS components and their combinations were observed across ethnicities. Increased blood pressure was commonly seen especially in Ghanaians, while South-Asian Surinamese and Turkish had higher MetS rates in general and were characterized by worse lipid-related measures. Regarding the gut microbiota, when ethnic-independent associations were assumed, a higher α-diversity, higher abundance of several ASVs (mostly for waist and triglyceride-related outcomes) and a trophic network of ASVs of Ruminococcaceae, Christensenellaceae, and Methanobrevibacter (RCM) bacteria were associated with better MetS outcomes. Statistically significant ethnic-specific associations were however noticed for α-diversity and the RCM trophic network. Associations were significant in the Dutch but not always in all other ethnicities. In Ghanaians, a higher α-diversity and RCM network abundance showed an aberrant positive association with high blood pressure measures compared to the other ethnicities. Even though adjustment for socioeconomic status-, lifestyle-, and diet-related variables often attenuated the effect size and/or the statistical significance of the ethnic-specific associations, an overall similar pattern across outcomes and ethnicities remained. CONCLUSIONS: The occurrence of MetS characteristics among ethnicities is heterogeneous. Both ethnic-independent and ethnic-specific associations were identified between the gut microbiota and MetS outcomes. Across multiple ethnicities, a one-size-fits-all approach may thus be reconsidered in regard to both the definition and/or treatment of MetS and its relation to the gut microbiota.

Healthy ageing in a multi-ethnic population: A descriptive cross-sectional analysis from the HELIUS study.

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.

Sex differences in blood pressure phenotypes over time - the HELIUS study.

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 aged < 45 years stratified according to baseline office BP into normotension (<140/<90 mmHg), isolated systolic hypertension (ISH, ≥140/<90 mmHg), isolated diastolic hypertension (IDH, <140/≥90 mmHg) or systolic diastolic hypertension (SDH, ≥140/≥90 mmHg). Logistic regression adjusted for age, ethnicity, and follow-up time was used to assess the risk of hypertension at follow-up (BP ≥140/90 mmHg or use of antihypertensive medication), stratified by sex. RESULTS: We included 4103 participants [mean age 33.5 years (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.

Networks of gut bacteria relate to cardiovascular disease in a multi-ethnic population: the HELIUS study.

AIMS: Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVDs). The composition and abundance of gut microbiota trophic networks differ between ethnicities. We aim to evaluate the relationship between gut microbiotal trophic networks and CVD phenotypes. METHODS AND RESULTS: We included cross-sectional data from 3860 individuals without CVD history from 6 ethnicities living in the Amsterdam region participating in the prospective Healthy Life in Urban Setting (HELIUS) study. Genetic variants were genotyped, faecal gut microbiota were profiled, and blood and anthropometric parameters were measured. A machine learning approach was used to assess the relationship between CVD risk (Framingham score) and gut microbiota stratified by ethnicity. Potential causal relationships between gut microbiota composition and CVD were inferred by performing two-sample Mendelian randomization with hard CVD events from the Pan-UK Biobank and microbiome genome-wide association studies summary data from a subset of the HELIUS cohort (n = 4117). Microbial taxa identified to be associated with CVD by machine learning and Mendelian randomization were often ethnic-specific, but some concordance across ethnicities was found. The microbes Akkermansia muciniphila and Ruminococcaceae UCG-002 were protective against ischaemic heart disease in African-Surinamese and Moroccans, respectively. We identified a strong inverse association between blood lipids, CVD risk, and the combined abundance of the correlated microbes Christensenellaceae-Methanobrevibacter-Ruminococcaceae (CMR). The CMR cluster was also identified in two independent cohorts and the association with triglycerides was replicated. CONCLUSION: Certain gut microbes can have a potentially causal relationship with CVD events, with possible ethnic-specific effects. We identified a trophic network centred around Christensenellaceae, Methanobrevibacter, and various Ruminococcaceae, frequently lacking in South-Asian Surinamese, to be protective against CVD risk and associated with low triglyceride levels.

Comparative Analysis of Taxonomic and Functional Gut Microbiota Profiles in Relation to Seroconversion of Thyroid Peroxidase Antibodies in Euthyroid Participants.

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.

Ethnic Differences in Carotid Intima Media Thickness and Plaque Presence - The HELIUS study.

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.

Serum Adiponectin and Leptin Among Ghanaian Migrants in Amsterdam and Their Compatriots in Rural and Urban Ghana: The RODAM Study.

Background: The rapidly rising cardiometabolic disease (CMD) burden in urbanizing sub-Saharan African populations and among sub-Saharan African migrants in Europe likely affects serum adiponectin and leptin levels, but this has not yet been quantified. Objectives: To compare the serum levels of adiponectin and leptin among migrant, and non-migrant (urban and rural) populations of Ghanaian descent. Methods: Cross-sectional analysis of serum leptin and adiponectin in the multi-centre Research on Obesity and Diabetes among African Migrants (RODAM) study. Logistic-regression models were used to examine the association between these adipocyte-derived hormones after stratification (sex, geographic area) and adjustments for potential confounders. Results: A total of 2518 Ghanaians were included. Rural participants had the highest serum adiponectin and lowest leptin levels compared to Amsterdam and urban Ghanaians (P < .001). In fully adjusted models, participants living in urban Ghana had significantly higher odds of hyperleptinemia compared to rural participants (women-odds ratio 2.88; 95% CI, 1.12-7.38, P = .028 and men 43.52, 95% CI, 4.84-391.25, P < .001). Urban Ghanaian men also had higher odds of elevated leptin: adiponectin ratio (6.29, 95% CI, 1.43-27.62, P = .015). The odds of hyperleptinemia were only higher in Amsterdam Ghanaian men (10.56; 95% CI, 1.11-100.85, P = .041), but not in women (0.85; 95% CI, 0.30-2.41, P = .759). There was no significant association between hypoadiponectinemia and geographical location in both sexes. Conclusion: Urbanization is associated with serum adiponectin and leptin levels after adjusting for confounding covariates in sub-Saharan Africans. These findings serve as a backdrop for further research on the role adipokines play in CMD epidemiology among Africans.

Association Between Self-Rated Medication Adherence and Adverse Cardiovascular Outcomes in Patients With Hypertension.

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.

Associations between spirometric impairments and microvascular complications in type 2 diabetes: a cross-sectional study.

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.

Salt-sensitive trait of normotensive individuals is associated with altered autonomous cardiac regulation: a randomized controlled intervention study.

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.

Macrovascular and renal microvascular complications in West Africans with intermediate hyperglycemia living in West Africa and Europe: The RODAM study.

Background: Metabolic conditions, including intermediate hyperglycemia (IH), affect migrants to a greater extent than the populations of origin. Evidence suggests that IH increases the risk of vascular complications, but it is unclear whether the differences in IH between the non-migrant and migrant populations translate to differences in vascular complications between the two populations. We compared the prevalence of macrovascular and renal microvascular complications among West Africans with IH living in West Africa and their migrant compatriots in Europe. Methods: Data from the multicenter Research on Obesity and Diabetes among African Migrants(RODAM) study were analyzed. Ghanaians with IH(524 non-migrant and 1439 migrants) were included. Logistic regression analyses were used to determine the associations between migrant status and macrovascular [coronary artery disease(CAD) and peripheral artery disease(PAD)] and renal microvascular[nephropathy] complications with adjustment for age, sex, socioeconomic status, smoking, systolic blood pressure, BMI, total cholesterol, HbA1c, C-reactive protein, and serum uric acid. Findings: The prevalence of microvascular/macrovascular complications was higher in non-migrants than in migrants(nephropathy 15.3vs.9.7%; PAD 3.1%vs.1.3%; and CAD 15.8% vs. 5.0%). The differences persisted in the fully adjusted model: nephropathy [odds ratio, 2.12; 95% CI(1.46-3.08); PAD, 4.44(1.87-10.51); CAD 2.35(1.64-3.37)]. Non-migrant females had higher odds of nephropathy[2.14(1.34-3.43)], PAD[7.47(2.38-23.40)] and CAD [2.10(1.34-3.27)] compared to migrant females. Non-migrant males had higher odds of nephropathy[2.54(1.30-4.97)] and CAD[2.85(1.48-5.50)], but not PAD[1.81(0.32-10.29)],than their migrant peers. Interpretation: Macrovascular and renal microvascular complications were more prevalent in non-migrants than in migrant West Africans with IH. Further studies are needed to identify factors that increase the risk to aid preventive/treatment strategies.

Assessment of renal sympathetic control using invasive pressure and flow velocity measurements in humans.

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.