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BACKGROUND: Blood pressure (BP) control among treated patients in Africa is very suboptimal, with low levels of combination therapy use and therapeutic inertia being among the major barriers to effective control of hypertension. The VERONICA-Nigeria study aims to evaluate, among Black African adults with hypertension, the effectiveness and safety of a triple pill-based treatment protocol compared to Nigeria hypertension treatment protocol (standard care protocol) for the treatment of hypertension. METHODS: This study involves a randomized, parallel-group and open-label trial. Adults with uncontrolled hypertension (n = 300), untreated or receiving monotherapy, with no contraindication to study treatments will be randomly assigned 1:1 to treatment with a triple pill based-treatment protocol or standard care protocol. Follow-up is for 6 months, with interim follow up visits at month 1, 2, and 3. In a noncomparative extension treatment period, participants completing the 6 months randomized period and on ≤3 BP-lowering drugs will receive treatment with the triple pill-based treatment protocol for 12 months. The primary outcome is change in home mean SBP from baseline to month 6, and key secondary efficacy outcome is percentage of participants with clinic BP <140/90 mmHg at month 6. The primary safety outcome is discontinuation of trial treatment due to adverse events from randomization to month 6. Economic evaluation will be conducted to assess the cost-effectiveness of the triple pill-based treatment protocol, and process evaluation will be conducted to understand the context in which the trial was conducted, implementation of the trial and interventions and mechanisms of effect, and potential barriers and facilitators to implementing the intervention in clinical practice. CONCLUSION: The VERONICA-Nigeria trial will provide evidence of effectiveness and safety of the triple-based treatment protocol for the pharmacological management of hypertension, in Black African adults. TRIAL REGISTRATION: PACTR202107579572114.
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BACKGROUND: Low-potassium intake is associated with a higher risk of type 2 diabetes and hypertension. Both conditions occur more frequently in Black populations, who also consume less potassium-rich foods. OBJECTIVES: Using metabolomics to identify dysregulated metabolic pathways associated with low-potassium excretion may procure more accurate entry points for nutritional prevention and intervention for type 2 diabetes and hypertension. METHODS: A total of 440 White and 350 Black adults from the African-PREDICT study (aged 20-30 y) were included. Twenty-four-hour blood pressure (BP) was measured. Potassium, sodium, and fasting glucose concentrations were analyzed in 24-h urine and plasma samples. Liquid chromatography-tandem mass spectrometry-based metabolomics included the analyses of amino acids and acylcarnitines in spot urine samples. RESULTS: Black participants had lower urinary potassium concentrations than Whites (36.6 compared with 51.1 mmol/d; P < 0.001). In White but not Black adults, urinary potassium correlated positively with 2-aminoadipic acid (2-AAA) (r = 0.176), C3-[propionyl]carnitine (r = 0.137), C4-[butyryl]carnitine (r = 0.169) and C5-[isovaleryl]carnitine (r = 0.167) in unadjusted and 2-AAA (r = 0.158) and C4-carnitine (r = 0.160) in adjusted analyses (all P < 0.05 and q < 0.05). Elevated C0-, C3-, and C5-carnitine in turn were positively associated with systolic BP (Black and White groups), diastolic BP (Black group), and glucose (White group) (all P < 0.05). CONCLUSIONS: Racial differences are an important consideration when investigating nutrient-metabolite relationships and the role thereof in cardiovascular disease. Only in White adults did urinary potassium associate with 2-AAA and short-chain acylcarnitines. These metabolites were positively related to BP and fasting plasma glucose concentrations. In White adults, the metabolomic profiles related to potassium excretion may contribute to BP regulation and glucose homeostasis. This trial was registered at clinicaltrials.gov as NCT03292094.
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Carnitina , Diabetes Mellitus Tipo 2 , Hipertensão , Adulto , Humanos , Pressão Sanguínea/fisiologia , Carnitina/análogos & derivados , Homeostase , Hipertensão/urina , Potássio/urinaRESUMO
BACKGROUND: Immune responses play a significant role in hypertension, though the importance of key inflammatory mediators remains to be defined. We used a systematic literature review and meta-analysis to study the associations between key cytokines and incident hypertension. METHODS: We performed a systematic search of Pubmed/Medline, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL), for peer-reviewed studies published up to August 2022. Incident hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg and/or the use of antihypertensive medications. Random effects meta-analyses were used to calculate pooled hazard ratios (HRs)/risk ratios (RRs) and 95% confidence intervals by cytokine levels (highest vs. lowest quartile). RESULTS: Only IL-6 and IL-1ß levels have evidence allowing for quantitative evaluation concerning the onset of hypertension. Six studies (10406 participants, 2932 incident cases) examined the association of IL-6 with incident hypertension. The highest versus lowest quartile of circulating IL-6 was associated with a significant HR/RR of hypertension (1.61, 95% CI: 1.00 to 2.60; I2 =87%). After adjusting for potential confounders, including body mass index (BMI), HR/RR was no longer significant (HR/RR: 1.24; 95% CI, 0.96 to 1.61; I2 = 56%). About IL-1ß, neither the crude (HR/RR: 1.03; 95% CI, 0.60 to 1.76; n = 2) nor multivariate analysis (HR/RR: 0.97, 95% CI, 0.60 to 1.56; n = 2) suggested a significant association with the risk of developing hypertension. CONCLUSIONS: A limited number of studies suggest that higher IL-6, but not IL-1ß, might be associated with the development of hypertension.
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Citocinas , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Citocinas/uso terapêutico , Hipertensão/epidemiologia , Hipertensão/tratamento farmacológico , Interleucina-1beta/farmacologia , Interleucina-6RESUMO
BACKGROUND AND AIMS: Potassium-enriched low sodium salt substitutes (LSSS), which replace a proportion of sodium chloride (NaCl) with potassium chloride (KCl), have been shown to reduce blood pressure and offer a potential solution to address the high burden of hypertension in South Africa. However, it is unknown which proportions of KCl in LSSS are acceptable. We compared the taste and visual acceptability of various LSSS in South African adults. METHODS AND RESULTS: Fifty-six adults underwent double-blind taste and visual tests of four LSSS (35%KCl/65%NaCl; 50%KCl/50%NaCl; 66%KCl/34%NaCl; 100%KCl) in comparison to 100%NaCl (common salt). Participants scored each product by taste ranking, taste perception and likeliness to use. Participants then visually inspected the five products and attempted to identify which was which. Almost half (45 %) of participants ranked the taste of 50%KCl/50 %NaCl as fantastic or really good. Furthermore, 62 % of participants liked and would be happy to use the 50 %KCl/50 %NaCl or felt this tasted like common salt. Only 12 % rated the 100%KCl highly for taste, and over half reported being unlikely to use this. Most participants (57.3 % and 36.4 %) were able to visually identify 100%NaCl and 100%KCl, while identification of other blends was generally poor. Responses were similar for 35%KCl/65%NaCl and 66%KCl/34%NaCl throughout. CONCLUSION: Our findings suggest that the taste of the 50%KCl salt substitute would be well tolerated by South African adults, most of which could not visually differentiate between this salt substitute and common salt.
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Cloreto de Sódio , Percepção Gustatória , Adulto , Humanos , Potássio , Cloreto de Potássio , Sódio , África do Sul , PaladarRESUMO
We participated in the UK and Republic of Ireland May Measurement Month 2021 (MMM21) campaign to raise awareness about blood pressure (BP) measurement and the dangers posed by elevated BP and hypertension. In addition, the campaign aimed to collect and report levels of BP awareness and control in the community setting. The MMM21 campaign set up opportunistic community screening sites at hospitals, general practice (GP) surgeries, community pharmacies, gyms, and various other public places. The campaign screened 1322 participants (mean age 46 years, 55% women) and found that 522 (39.5%) had hypertension (systolic BP ≥ 140â mmHg and/or diastolic BP ≥ 90â mmHg or on antihypertensive medication) at the time of testing. Of the 522 participants identified with hypertension, only 47.2% were aware of their condition. Of those on antihypertensive medication, only 45.7% had controlled BP (systolic BP < 140â mmHg and diastolic BP < 90â mmHg), and of all hypertensives, only 19.0% were controlled. Our UK and Ireland data continue to shed further light on low levels of awareness and control of hypertension in the UK and Ireland community setting. This evidence supports a critical need to further highlight the importance of identifying and taking action against raised BP.
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PURPOSE OF REVIEW: We summarise the physiological changes and risk factors for hypertension in females, potential sex-specific management approaches, and long-term prognosis. KEY FINDINGS: Pregnancy and menopause are two key phases of the life cycle where females undergo significant biological and physical changes, making them more prone to developing hypertension. Gestational hypertension occurs from changes in maternal cardiac output, kidney function, metabolism, or placental vasculature, with one in ten experiencing pregnancy complications such as intrauterine growth restriction and delivery complications such as premature birth. Post-menopausal hypertension occurs as the protective effects of oestrogen are reduced and the sympathetic nervous system becomes over-activated with ageing. Increasing evidence suggests that post-menopausal females with high blood pressure (BP) experience greater risk of cardiovascular events at lower BP thresholds, and greater vulnerability to treatment-related adverse effects. Hypertension is a key risk factor for cardiovascular disease in females. Current BP treatment guidelines and recommendations are similar for both sexes, without addressing sex-specific factors. Future investigations into ideal diagnostic thresholds, BP control targets and treatment regimens in females are needed.
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Hipertensão , Humanos , Feminino , Gravidez , Prognóstico , Hipertensão/fisiopatologia , Pós-Menopausa/fisiologia , Fatores de Risco , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologiaRESUMO
BACKGROUND AND AIMS: Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. METHODS: Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non-sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. RESULTS: A total of 460 980 and 14 462 patients were identified for the non-sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference -0.04 mmHg (95% confidence interval -0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. CONCLUSIONS: This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice.
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Doenças Cardiovasculares , Hipertensão , Infarto do Miocárdio , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Pressão Sanguínea , Hipertensão/complicações , Acetaminofen/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Sódio , Bicarbonato de Sódio/farmacologia , Infarto do Miocárdio/complicaçõesRESUMO
Hypertension is one of the most important and complex risk factors for cardiovascular diseases (CVDs). By using urinary peptidomics analyses, we aimed to identify peptides associated with hypertension, building a framework for future research towards improved prediction and prevention of premature development of CVD. We included 78 hypertensive and 79 normotensive participants from the African-PREDICT study (aged 20-30 years), matched for sex (51% male) and ethnicity (49% black and 51% white). Urinary peptidomics data were acquired using capillary-electrophoresis-time-of-flight-mass-spectrometry. Hypertension-associated peptides were identified and combined into a support vector machine-based multidimensional classifier. When comparing the peptide data between the normotensive and hypertensive groups, 129 peptides were nominally differentially abundant (Wilcoxon p < 0.05). Nonetheless, only three peptides, all derived from collagen alpha-1(III), remained significantly different after rigorous adjustments for multiple comparisons. The 37 most significant peptides (all p ≤ 0.001) served as basis for the development of a classifier, with 20 peptides being combined into a unifying score, resulting in an AUC of 0.85 in the ROC analysis (p < 0.001), with 83% sensitivity at 80% specificity. Our study suggests potential value of urinary peptides in the classification of hypertension, which could enable earlier diagnosis and better understanding of the pathophysiology of hypertension and premature cardiovascular disease development.
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Hipertensão , Proteômica , Humanos , Masculino , Adulto Jovem , Feminino , Biomarcadores , Proteômica/métodos , Peptídeos/química , Espectrometria de Massas/métodosRESUMO
Increased arterial stiffness is related to early vascular aging and is an independent predictor for cardiovascular disease and mortality. Molecular mechanisms underlying increased arterial stiffness are largely unexplored, especially at the proteome level. We aimed to explore the relationship between pulse wave velocity and urinary proteomics. We included 919 apparently healthy (no chronic illnesses) Black and White men and women (equally distributed) between 20 and 30 years from the African-PREDICT study. Capillary electrophoresis time-of-flight mass spectrometry was used to analyze the urinary proteome. We measured the carotid-femoral pulse wave velocity to estimate arterial stiffness. In the total group, pulse wave velocity correlated positively with collagen-derived peptides including collagen types I, II, III, IV, V, and IX and inversely with collagen type XI (adjusted for mean arterial pressure). Regarding noncollagen-derived peptides, pulse wave velocity positively correlated with polymeric immunoglobulin receptor peptides (n = 2) (all q-value ≤0.05). In multivariable adjusted analyses, pulse wave velocity associated positively and independently with seven urinary peptides (collagen type I, n = 5) (all p-value ≤0.05). We found significant positive and independent associations between pulse wave velocity and the collagen type I-derived peptides, suggesting that dysregulation of collagen type I in the extracellular matrix scaffold could lead to early onset of increased arterial stiffness.
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Análise de Onda de Pulso , Rigidez Vascular , Masculino , Humanos , Feminino , Colágeno Tipo I , Proteoma , Rigidez Vascular/fisiologia , Colágeno , Peptídeos , Pressão SanguíneaRESUMO
BACKGROUND: Despite high blood pressure being the leading preventable risk factor for death, only 1 in 3 patients achieve target blood pressure control. Key contributors to this problem are clinical inertia and uncertainties in relying on clinic blood pressure measurements to make treatment decisions. METHODS: The NEXTGEN-BP open-label, multicenter, randomized controlled trial will investigate the efficacy, safety, acceptability and cost-effectiveness of a wearable blood pressure monitor-based care strategy for the treatment of hypertension, compared to usual care, in lowering clinic blood pressure over 12 months. NEXTGEN-BP will enroll 600 adults with high blood pressure, treated with 0 to 2 antihypertensive medications. Participants attending primary care practices in Australia will be randomized 1:1 to the intervention of a wearable-based remote care strategy or to usual care. Participants in the intervention arm will undergo continuous blood pressure monitoring using a wrist-wearable cuffless device (Aktiia, Switzerland) and participate in 2 telehealth consultations with their primary care practitioner (general practitioner [GP]) at months 1 and 2. Antihypertensive medication will be up-titrated by the primary care practitioner at the time of telehealth consults should the percentage of daytime blood pressure at target over the past week be <90%, if clinically tolerated. Participants in the usual care arm will have primary care consultations according to usual practice. The primary outcome is the difference between intervention and control in change in clinic systolic blood pressure from baseline to 12 months. Secondary outcomes will be assessed at month 3 and month 12, and include acceptability to patients and practitioners, cost-effectiveness, safety, medication adherence and patient engagement. CONCLUSIONS: NEXTGEN-BP will provide evidence for the effectiveness and safety of a new paradigm of wearable cuffless monitoring in the management of high blood pressure in primary care. TRIAL REGISTRATION: ACTRN12622001583730.
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Hipertensão , Dispositivos Eletrônicos Vestíveis , Adulto , Humanos , Pressão Sanguínea/fisiologia , Anti-Hipertensivos/uso terapêutico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Atenção Primária à Saúde/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
INTRODUCTION: Increased exposure to risk factors in the young and healthy contributes to arterial changes, which may be accompanied by an altered metabolism. OBJECTIVES: To increase our understanding of early metabolic alterations and how they associate with markers of arterial stiffness, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and in a control group without CVD risk factors. METHODS: We included healthy black and white women and men (N = 1202), aged 20-30 years with a detailed CVD risk factor profile, reflecting obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036) and the control group (N = 166). Markers of arterial stiffness, central systolic blood pressure (BP) and pulse wave velocity were measured. A targeted metabolomics approach was followed by measuring amino acids and acylcarnitines using a liquid chromatography-tandem mass spectrometry method. RESULTS: In the CVD risk group, central systolic BP (adjusted for age, sex, ethnicity) was negatively associated with histidine, arginine, asparagine, serine, glutamine, dimethylglycine, threonine, GABA, proline, methionine, pyroglutamic acid, aspartic acid, glutamic acid, branched chain amino acids (BCAAs) and butyrylcarnitine (all P ≤ 0.048). In the same group, pulse wave velocity (adjusted for age, sex, ethnicity, mean arterial pressure) was negatively associated with histidine, lysine, threonine, 2-aminoadipic acid, BCAAs and aromatic amino acids (AAAs) (all P ≤ 0.044). In the control group, central systolic BP was negatively associated with pyroglutamic acid, glutamic acid and dodecanoylcarnitine (all P ≤ 0.033). CONCLUSION: In a group with increased CVD risk, markers of arterial stiffness were negatively associated with metabolites related to AAA and BCAA as well as energy metabolism and oxidative stress. Our findings may suggest that metabolic adaptations may be at play in response to increased CVD risk to maintain cardiovascular integrity.
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Doenças Cardiovasculares , Rigidez Vascular , Masculino , Humanos , Feminino , Adulto Jovem , Fatores de Risco , Metabolômica/métodos , Rigidez Vascular/fisiologia , Histidina , Ácido Pirrolidonocarboxílico , Análise de Onda de Pulso/efeitos adversos , Aminoácidos de Cadeia Ramificada , Fatores de Risco de Doenças Cardíacas , TreoninaRESUMO
In recent decades low- and middle-income countries (LMICs) have been witnessing a significant shift toward raised blood pressure; yet in LMICs, only 1 in 3 are aware of their hypertension status, and ≈8% have their blood pressure controlled. This rising burden widens the inequality gap, contributes to massive economic hardships of patients and carers, and increases costs to the health system, facing challenges such as low physician-to-patient ratios and lack of access to medicines. Established risk factors include unhealthy diet (high salt and low fruit and vegetable intake), physical inactivity, tobacco and alcohol use, and obesity. Emerging risk factors include pollution (air, water, noise, and light), urbanization, and a loss of green space. Risk factors that require further in-depth research are low birth weight and social and commercial determinants of health. Global actions include the HEARTS technical package and the push for universal health care. Promising research efforts highlight that successful interventions are feasible in LMICs. These include creation of health-promoting environments by introducing salt-reduction policies and sugar and alcohol tax; implementing cost-effective screening and simplified treatment protocols to mitigate treatment inertia; pooled procurement of low-cost single-pill combination therapy to improve adherence; increasing access to telehealth and mHealth (mobile health); and training health care staff, including community health workers, to strengthen team-based care. As the blood pressure trajectory continues creeping upward in LMICs, contextual research on effective, safe, and cost-effective interventions is urgent. New emergent risk factors require novel solutions. Lowering blood pressure in LMICs requires urgent global political and scientific priority and action.
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Países em Desenvolvimento , Hipertensão , Consumo de Bebidas Alcoólicas/efeitos adversos , Monitores de Pressão Arterial/normas , Monitores de Pressão Arterial/provisão & distribuição , COVID-19/complicações , COVID-19/epidemiologia , Fenômenos Fisiológicos Cardiovasculares , Países em Desenvolvimento/estatística & dados numéricos , Dieta/efeitos adversos , Meio Ambiente , Poluição Ambiental/efeitos adversos , Comportamentos Relacionados com a Saúde , Cardiopatias/mortalidade , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/etiologia , Perspectiva de Curso de Vida , Estilo de Vida , Enfermeiras e Enfermeiros/provisão & distribuição , Obesidade/complicações , Médicos/provisão & distribuição , Prevalência , Pesquisa , Fatores de Risco , Comportamento Sedentário , Determinantes Sociais da Saúde , Acidente Vascular Cerebral/mortalidade , Uso de Tabaco/efeitos adversos , UrbanizaçãoRESUMO
PURPOSE OF REVIEW: Sodium glucose transporter 2 inhibitors (SGLT2 inhibitors) are increasingly prescribed due to their considerable benefits on clinical outcomes in people with diabetes, heart failure, and chronic kidney disease (CKD). Hypertension is a common comorbidity in each of these disease states, increasing risk of cardiovascular morbidity and mortality. We herein review the effects of SGLT2 inhibitors on blood pressure in different populations, proposed mechanisms of action, and the contribution of blood pressure lowering to end-organ protection. RECENT FINDINGS: A recognised effect of SGLT2 inhibitors in recent clinical trials is blood pressure lowering, with multiple postulated mechanisms. This advantageous effect was first identified in populations with type 2 diabetes mellitus, prior to expansion of these trials to broader cohorts. On our review, we identified that the blood pressure lowering effect of SGLT2 inhibitors appears to be a dose-independent class-effect, with a magnitude of effect comparable to that seen with a low dose hydrochlorothiazide. There is considerable evidence demonstrating that this effect is observed across populations including those with type 2 diabetes mellitus, chronic kidney disease, and resistant hypertension.
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Diabetes Mellitus Tipo 2 , Hipertensão , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes , Pressão Sanguínea/fisiologia , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
BACKGROUND AND AIMS: Risk factor exposure from young ages was shown to contribute to cardiovascular events - cardiac hypertrophy, which may be accompanied by an altered metabolism. To determine how early metabolic alterations associate with myocardial structural changes, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and a control group without CVD risk factors. METHODS AND RESULTS: We included healthy adults (N = 1202), aged 20-30 years, stratified based on risk factors, i.e., obesity, physical inactivity, elevated blood pressure (BP), hyperglycemia, dyslipidemia, low socio-economic status, smoking and excessive alcohol use - forming the CVD risk group (N = 1036) and the control group (N = 166). Relative wall thickness (RWT) and left ventricular mass index (LVMi) were measured using echocardiography. Targeted metabolomics data were obtained using a liquid chromatography-tandem mass spectrometry method. Clinic systolic BP, 24 h BP and RWT were higher in the CVD risk group compared to the control group (all P ≤ 0.031). Exclusively in the CVD risk group, RWT associated with creatine and dodecanoylcarnitine; while LVMi associated with glycine, serine, glutamine, threonine, alanine, citrulline, creatine, proline, pyroglutamic acid and glutamic acid (all P ≤ 0.040). Exclusively in the control group, LVMi associated with propionylcarnitine and butyrylcarnitine (all P ≤ 0.009). CONCLUSION: In young adults without CVD, but with CVD risk factors, LVMi and RWT associated with metabolites linked energy metabolism (shifting from solely fatty acid oxidation to glycolysis, with impaired creatine kinase activity) and oxidative stress. Our findings support early onset metabolic changes accompanying cardiac structural alterations due to lifestyle and behavioural risk factors.
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Creatina , Hipertensão , Humanos , Adulto Jovem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Fatores de Risco , Metabolômica , Redes e Vias MetabólicasRESUMO
BACKGROUND: There is a dearth of comprehensive studies examining the burden and trends of hypertensive heart disease (HHD) and high systolic blood pressure (SBP) among the Australian population. We aimed to explore the burden of HHD and high SBP, and how they changed over time from 1990 to 2019 in Australia. METHODS: We analysed data from the Global Burden of Disease study in Australia. We assessed the prevalence, mortality, disability-adjusted life-years (DALY), years lived with disability (YLD) and years of life lost (YLL) attributable to HHD and high SBP. Data were presented as point estimates with 95% uncertainty intervals (UI). We compared the burden of HHD and high SBP in Australia with World Bank defined high-income countries and six other comparator countries with similar sociodemographic characteristics and economies. RESULTS: From 1990 to 2019, the burden of HHD and high SBP in Australia reduced. Age standardised prevalence rate of HHD was 119.3 cases per 100,000 people (95% UI 86.6-161.0) in 1990, compared to 80.1 cases (95% UI 57.4-108.1) in 2019. Deaths due to HDD were 3.4 cases per 100,000 population (95% UI 2.6-3.8) in 1990, compared to 2.5 (95% UI 1.9-3.0) in 2019. HHD contributed to 57.2 (95% UI 46.6-64.7) DALYs per 100,000 population in 1990 compared to 38.4 (95% UI 32.0-45.2) in 2019. Death rates per 100,000 population attributable to high SBP declined significantly over time for both sexes from 1990 (155.6 cases; 95% UI 131.2-177.0) to approximately one third in 2019 (53.8 cases; 95% UI 43.4-64.4). Compared to six other countries in 2019, the prevalence of HHD was highest in the USA (274.3%) and lowest in the UK (52.6%), with Australia displaying the third highest prevalence. Australia ranked second in term of lowest rates of deaths and third for lowest DALYs respectively due to high SBP. From 1990-2019, Australia ranked third best for reductions in deaths and DALYs due to HHD and first for reductions in deaths and DALYs due to high SBP. CONCLUSION: Over the past three decades, the burden of HHD in Australia has reduced, but its prevalence remains relatively high. The contribution of high SBP to deaths, DALYs and YLLs also reduced over the three decades.
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Carga Global da Doença , Cardiopatias , Masculino , Feminino , Humanos , Anos de Vida Ajustados por Qualidade de Vida , Pressão Sanguínea , Austrália/epidemiologiaRESUMO
BACKGROUND: People with type 2 diabetes and chronic kidney disease experience a high burden of hypertension, but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population are uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP-lowering therapy is also unknown. METHODS: The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) randomized people with type 2 diabetes and chronic kidney disease to canagliflozin or placebo. In a post hoc analysis, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP-lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mm Hg while receiving ≥3 classes of BP-lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups. RESULTS: The trial included 4401 participants, of whom 3361 (76.4%) had baseline systolic BP ≥130 mm Hg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50 mm Hg (95% CI, -4.27 to -2.72), an effect maintained over the duration of the trial, with similar reductions across BP and BP-lowering therapy subgroups (all P interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP-lowering agents during the trial (hazard ratio, 0.68 [95% CI, 0.61-0.75]). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death caused by kidney or cardiovascular disease (hazard ratio, 0.70 [95% CI, 0.59-0.82]) was consistent across BP and BP-lowering therapy subgroups (all P interaction ≥0.35), as were effects on other key kidney, cardiovascular, and safety outcomes. CONCLUSIONS: In people with type 2 diabetes and chronic kidney disease, canagliflozin lowers systolic BP across all BP-defined subgroups and reduces the need for additional BP-lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP-lowering therapy in people with chronic kidney disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.
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Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Insuficiência Renal Crônica/induzido quimicamente , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologiaRESUMO
Raised blood pressure (BP) is the leading cause of death and disability worldwide, and its particular strong association with stroke is well established. Although systolic BP increases with age in both sexes, raised BP is more prevalent in males in early adulthood, overtaken by females at middle age, consistently across all ethnicities/races. However, there are clear regional differences on when females overtake males. Higher BP among males is observed until the seventh decade of life in high-income countries, compared with almost 3 decades earlier in low- and middle-income countries. Females and males tend to have different cardiovascular disease risk profiles, and many lifestyles also influence BP and cardiovascular disease in a sex-specific manner. Although no hypertension guidelines distinguish between sexes in BP thresholds to define or treat hypertension, observational evidence suggests that in terms of stroke risk, females would benefit from lower BP thresholds to the magnitude of 10 to 20 mm Hg. More randomized evidence is needed to determine if females have greater cardiovascular benefits from lowering BP and whether optimal BP is lower in females. Since 1990, the number of people with hypertension worldwide has doubled, with most of the increase occurring in low- and-middle-income countries where the greatest population growth was also seen. Sub-Saharan Africa, Oceania, and South Asia have the lowest detection, treatment, and control rates. High BP has a more significant effect on the burden of stroke among Black and Asian individuals than Whites, possibly attributable to differences in lifestyle, socioeconomic status, and health system resources. Although pharmacological therapy is recommended differently in local guidelines, recommendations on lifestyle modification are often very similar (salt restriction, increased potassium intake, reducing weight and alcohol, smoking cessation). This overall enhanced understanding of the sex- and ethnic/racial-specific attributes to BP motivates further scientific discovery to develop more effective prevention and treatment strategies to prevent stroke in high-risk populations.
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Doenças Cardiovasculares , Hipertensão , Acidente Vascular Cerebral , Adulto , Pressão Sanguínea , Doenças Cardiovasculares/complicações , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Grupos Raciais , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND: High dietary sodium intake is a leading cause of hypertension. A major source of dietary sodium is salt added to processed food products available in retail food environments. The fast-growing online grocery shopping setting provides new opportunities for salt reduction interventions that support consumers in choosing healthier options. METHODS: The SaltSwitch Online Grocery Shopping randomized controlled trial is investigating the feasibility, acceptability, and effectiveness of a novel intervention for lowering salt consumption and blood pressure amongst people with hypertension who shop for groceries online. The intervention is based on a bespoke web browser extension that interfaces with a major retailer's online store to highlight and interpret product sodium content and suggest similar but lower-sodium alternatives. The primary outcome of interest is change in mean systolic blood pressure between individuals randomized (1:1) to the intervention and control (usual online shopping) arms at 12 weeks. Secondary outcomes are diastolic blood pressure, spot urinary sodium and sodium:potassium ratio, sodium purchases, and dietary intake. Intervention implementation and lessons for future uptake will be assessed using a mixed methods process evaluation. Participants with hypertension who shop online for groceries and exhibit high sodium purchasing behavior are being recruited across Australia. A target sample size of 1,966 provides 80% power (2-sided alpha = 0.05) to detect a 2 mm Hg difference in systolic blood pressure between groups, assuming a 15 mm Hg standard deviation, after allowing for a 10% dropout rate. DISCUSSION: This trial will provide evidence on an innovative intervention to potentially reduce salt intake and blood pressure in people with hypertension. The intervention caters to individual preferences by encouraging sustainable switches to similar but lower-salt products. If effective, the intervention will be readily scalable at low cost by interfacing with existing online retail environments.
Assuntos
Hipertensão , Hipotensão , Sódio na Dieta , Pressão Sanguínea , Humanos , Hipotensão/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Sódio , Cloreto de Sódio na DietaRESUMO
AIM: To define the proportional and absolute benefits of the sodium-glucose co-transporter-2 inhibitor canagliflozin in patients with type 2 diabetes (T2D) with and without peripheral arterial disease (PAD). MATERIALS AND METHODS: We pooled individual participant data from the CANVAS Program (n = 10 142) and CREDENCE trial (n = 4401). In this post hoc analysis, the main outcomes of interest were major adverse cardiovascular events (MACE: non-fatal myocardial infarction, non-fatal stroke or cardiovascular death), kidney outcomes, and extended major adverse limb events (MALE). Cox proportional hazards models were used to assess canagliflozin treatment effects in those with and without PAD. Absolute risk reductions per 1000 patients treated for 2.5 years were estimated using Poisson regression. RESULTS: Of 14 543 participants, 3159 (21.7%) had PAD at baseline. In patients with PAD, canagliflozin reduced MACE (hazard ratio, 0.76; 95% confidence interval, 0.62-0.92), with similar relative benefits for other cardiovascular and kidney outcomes in participants with or without PAD at baseline (all Pinteraction > .268). There was no increase in the relative risk of extended MALE with canagliflozin, irrespective of baseline PAD history (Pinteraction > .864). The absolute benefits of canagliflozin were greater in those with PAD. CONCLUSIONS: Patients with T2D and PAD derived similar relative cardiorenal benefits from canagliflozin treatment but higher absolute benefits compared with those without PAD, with no increase in extended MALE.
Assuntos
Canagliflozina , Diabetes Mellitus Tipo 2 , Doença Arterial Periférica , Canagliflozina/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Nefropatias/epidemiologia , Doença Arterial Periférica/complicações , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversosRESUMO
OBJECTIVE: Single-pill combination (SPC) therapy is recommended as first-line therapy for most patients in global hypertension guidelines due to benefits of improved adherence and blood pressure (BP) control. We aimed to understand factors affecting SPC use in the management of raised BP in Australia. DESIGN: A mixed-method study comprising of qualitative (policy review and interviews) and quantitative (Pharmaceutical Benefits Scheme [PBS] data) approaches. MAIN OUTCOME MEASURES: Australian and international hypertension guideline recommendations regarding SPC use; the Australian registration and subsidy approval processes of SPCs; use of SPCs on the PBS; cost-analysis of PBS-listed SPCs compared to free-drug combinations; perceptions of healthcare providers towards SPCs. RESULTS: The 2016 Australian Heart Foundation's "Guideline for the diagnosis and management of hypertension in adults" does not recommend combination therapy (including SPCs) as first-line treatment. Additional challenges in the uptake of SPCs include: (1) the additional PBS requirements and barriers imposed for the listing of SPCs. (2) Script volumes for SPCs have not matched the rise in the number of SPCs listed for subsidy, have plateaued since 2016 and remained significantly lower than single constituent scripts. (3) SPCs are not subsidised by the PBS for initial treatment. Most SPCs provided substantial cost savings for individual patients compared to free-drug combinations. Health care providers were positive about the cost-saving and convenience of SPCs, however perceived negatives included inflexibility of SPCs during dose titration, medicine shortages, and potential adverse effects when initiating treatment with multiple drugs. CONCLUSION: The safety, efficacy and cost-saving potential of SPCs have been established in the literature but several roadblocks in the existing health system in Australia impede uptake. Interventions addressing these barriers may facilitate improved uptake, which may in turn improve blood pressure control in Australia.