RESUMO
OBJECTIVE: To explore in a primary care setting the associations between patients' daily self-measured blood pressure (BP) during eight weeks and concurrent self-reported values of wellbeing, lifestyle, symptoms, and medication intake. We also explore these associations for men and women separately. DESIGN AND SETTING: The study is a secondary post-hoc analysis of the randomised controlled trial PERson-centeredness in Hypertension management using Information Technology (PERHIT). The trial was conducted in primary health care in four regions in Southern Sweden. PATIENTS: Participants (n = 454) in the intervention group in the PERHIT-trial used an interactive web-based system for self-management of hypertension for eight consecutive weeks. Each evening, participants reported in the system their wellbeing, lifestyle, symptoms, and medication adherence as well as their self-measured BP and heart rate. MAIN OUTCOME MEASURES: Association between self-reported BP and 10 self-report lifestyle-related variables. RESULTS: Self-reported less stress and higher wellbeing were similarly associated with BP, with 1.0 mmHg lower systolic BP and 0.6/0.4 mmHg lower diastolic BP (p < 0.001). Adherence to medication had the greatest impact on BP levels (5.2/2.6 mmHg, p < 0.001). Restlessness and headache were also significantly associated with BP, but to a lesser extent. Physical activity was only significantly associated with BP levels for men, but not for women. CONCLUSION: In hypertension management, it may be important to identify patients with high-stress levels and low wellbeing. The association between medication intake and BP was obvious, thus stressing the importance of medication adherence for patients with hypertension.
Associations between daily home blood pressure (BP) and self-reports of lifestyle and symptoms have not been previously well explored.Self-reported higher wellbeing, lower restlessness, less stress, and higher medication adherence were significantly associated with lower same-day BP levels.Physical activity was significantly associated with same-day BP for men, but not for women.Using a hypertension management system may be a valuable tool for communication between the patient and physician.
Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Hipertensão , Estilo de Vida , Adesão à Medicação , Atenção Primária à Saúde , Autorrelato , Humanos , Feminino , Masculino , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Suécia , Idoso , Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Adulto , Autocuidado , Frequência Cardíaca , Estresse PsicológicoRESUMO
ABSTRACT: We have previously shown increased vascular reactivity to angiotensin (Ang) II in familial combined hyperlipidemia. However, this has not been well studied in familial hypercholesterolemia (FH), a condition with incipient endothelial dysfunction. This study aimed to examine microvascular and macrovascular responses to Ang II in FH. Therefore, we investigated the effects of a 3-hour infusion of Ang II on blood pressure and forearm skin microvascular function in 16 otherwise healthy patients with FH and matched healthy controls. Skin microvascular hyperemia was studied by laser Doppler fluxmetry during local heating. Microvascular resistance was determined by the ratio of mean arterial pressure to microvascular hyperemia. Macrovascular reactivity was assessed by changes in brachial blood pressure. Compared with the controls, the FH group had increased baseline systolic blood pressure (127 ± 14 vs. 115 ± 12 mm Hg; P = 0.02), while systolic blood pressure responses were similar (+24 ± 9 vs. +21 ± 7 mm Hg; P = 0.26) after 3 hours of Ang II infusion. At baseline, there were no group differences in microvascular hyperemia or resistance. However, after 3 hours of Ang II infusion, heat-induced microvascular hyperemia was less pronounced in FH (126 ± 95 vs. 184 ± 102 arbitrary units; P = 0.01), while microvascular resistance during heat-induced hyperemia was increased (1.9 ± 0.9 vs. 0.9 ± 0.8, P = 0.01), as compared to controls. Both these responses were further pronounced 1 hour after stopping Ang II. In conclusion, despite similar blood pressure responses to Ang II in the FH group and controls, microvascular dilatation capacity was impaired in the FH group, indicating endothelial dysfunction. These findings and increased microvascular resistance may lead to hypertension and microvascular complications in FH.
Assuntos
Angiotensina II/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Artéria Braquial/efeitos dos fármacos , Hiperlipoproteinemia Tipo II/fisiopatologia , Microcirculação/efeitos dos fármacos , Pele/irrigação sanguínea , Vasodilatação/efeitos dos fármacos , Adulto , Angiotensina II/sangue , Artéria Braquial/fisiopatologia , Estudos de Casos e Controles , Feminino , Antebraço , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Infusões Intravenosas , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We examined the contribution of the angiotensin-converting enzyme inhibitor ramipril and the alpha 1-adrenergic receptor blocker doxazosin on blood pressure and on markers of inflammation and hemostasis in 59 individuals with mild-to-moderate hypertension randomized to receive double-blind ramipril 10 mg od or doxazosin 8 mg od for 12 weeks. Inflammatory markers (interleukin-6, soluble interleukin-6 receptor, interleukin-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and C-reactive protein) and hemostasis (plasminogen activator inhibitor-1 activity, tissue plasminogen activator antigen, thrombin-antithrombin complex, and thrombin generation by calibrated automated thrombogram) were assessed. The treatment reduced blood pressure in both groups. Thrombin-antithrombin complex decreased by treatment, and this was dependent on a reduction in thrombin-antithrombin complex in the ramipril group alone. There were no changes in plasminogen activator inhibitor-1 activity, whereas tissue plasminogen activator antigen increased by ramipril and decreased by doxazosin. Only minor changes were observed in systemic inflammation by treatment. Treatment with ramipril seems to reduce thrombin generation beyond effects on reducing blood pressure. Drugs blocking the renin-angiotensin-aldosterone system may reduce atherothrombotic complications beyond their effects to reduce blood pressure.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Doxazossina/uso terapêutico , Hemostasia/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Inflamação/tratamento farmacológico , Ramipril/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Biomarcadores/sangue , Método Duplo-Cego , Doxazossina/efeitos adversos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/fisiopatologia , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Ramipril/efeitos adversos , Suécia , Fatores de Tempo , Resultado do TratamentoRESUMO
Blood pressure variability (BPV) represents a cardiovascular risk factor, regardless of mean level of blood pressure (BP). In this post-hoc analysis from the PERson-centredness in Hypertension management using Information Technology (PERHIT) study, we aimed to explore BPV in daily home measurements in hypertensive patients from primary care, to identify factors associated with high BPV and to investigate whether estimated glomerular filtration rate (eGFR) and pulse pressure, as markers of target organ damage (TOD), are associated with BPV. For eight consecutive weeks, 454 participants reported their daily BP and heart rate in their mobile phone, along with reports of lifestyle and hypertension-related factors. Systolic BP (SBP) values were used to calculate BPV with coefficient of variation (CV) as primary estimate. Background characteristics and self-reports were tested between fifths of CV in a linear regression model, adjusted for age and sex. Associations between BPV and eGFR and pulse pressure were tested with linear and logistic regression models. Higher home BPV was associated with higher age, BP, heart rate, and smoking. BPV was lower for participants with low alcohol consumption and treatment with calcium channel blockers. There was a significant association between BPV and pulse pressure (P = 0.015), and between BPV and eGFR (P = 0.049). Participants with high BPV reported more dizziness and palpitations. In conclusion, pulse pressure and eGFR were significantly associated with home BPV. Older age, high BP, heart rate, and smoking were associated with high BPV, but treatment with calcium channel blockers and low alcohol consumption was associated with low BPV. Trial registration: The study was registered with ClinicalTrials.gov [NCT03554382].
Assuntos
Bloqueadores dos Canais de Cálcio , Hipertensão , Humanos , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Rim , Atenção Primária à SaúdeRESUMO
The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.
Assuntos
Predisposição Genética para Doença , Genômica , Hipertensão/genética , Rim/patologia , Processamento Alternativo/genética , Pressão Sanguínea/genética , Metilação de DNA/genética , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genéticaRESUMO
OBJECTIVES: Calcium antagonists are vasodilating drugs, which may cause reflex activation of the sympathetic nervous system with potentially untoward effects. We studied the effects of long-term treatment with amlodipine, a long-acting dihydropyridine-type calcium antagonist, and mibefradil, a phenylalkylamine-type calcium antagonist, on sympathetic nerve activity. METHODS: Fourteen patients with primary hypertension participated in a double-blind, cross-over study comparing the effects of 6 weeks of treatment with mibefradil 100 mg daily and amlodipine 10 mg daily. Heart rate, direct arterial blood pressure and cardiac output by echocardiography were registered. Global sympathetic activity was estimated using a [3H]noradrenaline isotope dilution method with arterial and venous sampling; cardiac sympathetic activity was assessed indirectly by heart rate variability and tissue velocity echocardiography. RESULTS: Both drugs lowered mean arterial pressure; the decrease was more pronounced with mibefradil (from 118 +/- 3 to 99 +/- 2 mmHg, compared to 118 +/- 3 to 104 +/- 2 mmHg for amlodipine, P < 0.01 between drugs). Mibefradil decreased heart rate (66 +/- 2 to 57 +/- 2 bpm), whereas amlodipine caused a slight increase (66 +/- 2 to 70 +/- 2 bpm; P < 0.001 between drugs) and tended to increase cardiac output. Noradrenaline spillover increased similarly with the two drugs, from 3.44 +/- 0.27 to 5.20 +/- 0.48 nmol/min per m2(P < 0.01) during mibefradil and to 5.72 +/- 0.49 nmol/min per m2 (P < 0.001) during amlodipine. There were minor effects on cardiac sympatho-vagal balance, but systolic and diastolic myocardial velocities were increased similarly by both drugs. CONCLUSIONS: Mibefradil and amlodipine treatment increase global sympathetic nerve activity similarly during long-term treatment, despite opposite effects on heart rate. Increases in myocardial velocities suggest concomitant cardiac sympathetic activation.
Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/tratamento farmacológico , Mibefradil/uso terapêutico , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Anlodipino/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Débito Cardíaco/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Coração/inervação , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Masculino , Mibefradil/farmacologia , Pessoa de Meia-Idade , Norepinefrina/sangue , Fatores de Tempo , UltrassonografiaRESUMO
Impaired fibrinolysis is related to insulin resistance, also a characteristic feature of familial combined hyperlipidemia (FCHL). The renin-angiotensin (Ang) system is upregulated with insulin resistance, and there is crosstalk between Ang II and insulin-signalling pathways. We studied the fibrinolytic effects of a 3-h systemic Ang II infusion in 16 patients with FCHL and 16 controls, and placebo infusion in eight individuals. Baseline plasminogen activator inhibitor-1 (PAI-1) activity, plasmin-antiplasmin complex, insulin resistance and C-reactive protein were higher in patients with FCHL than in controls. PAI-1 activity decreased during Ang II, similar in patients with FCHL and controls, and by placebo. Plasmin-antiplasmin complex was unaffected by Ang II in FCHL but increased in controls. Patients with FCHL show signs of insulin resistance, low-grade inflammation and impaired fibrinolysis. Ang II enhances fibrinolysis in controls but not in patients with FCHL, suggesting that patients with FCHL are not capable of increasing tissue plasminogen activator activity in response to Ang II. Ang II has no short-term effects on PAI-1 activity.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Fibrinólise/efeitos dos fármacos , Hiperlipidemia Familiar Combinada/genética , Hiperlipidemia Familiar Combinada/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Angiotensina II/administração & dosagem , Feminino , Voluntários Saudáveis , Humanos , MasculinoRESUMO
INTRODUCTION: We examined potential prothrombotic and proinflammatory effects of angiotensin II in 16 otherwise healthy familial hypercholesterolaemia subjects and 16 matched controls. METHODS: Markers of fibrinolysis, thrombin generation and inflammation were assessed in plasma before, during and 1h after a 3h intravenous infusion of angiotensin II. In addition, placebo experiments with saline infusion were carried out. RESULTS: Baseline plasminogen activator inhibitor type-1 activity and plasmin-antiplasmin-complex concentrations were similar in FH and controls, as were interleukin-6, leukocyte counts and C-reactive protein. Fibrinogen levels were higher in FH, and we observed a greater thrombin generating potential in FH (calibrated automated thrombogram), but no signs of elevated thrombin generation in vivo (prothrombin fragment 1+2). During angiotensin infusion plasminogen activator inhibitor type-1 activity decreased and plasmin-antiplasmin-complex concentrations increased similarly in FH and controls. Total and maximal amount of thrombin generated was unchanged, as were prothrombin-fragment-1+2 levels. Interleukin-6 and leukocyte counts increased similarly in both groups during angiotensin infusion, while fibrinogen tended to increase in FH and increased in controls. During saline infusion plasminogen activator inhibitor type-1 activity and prothrombin fragment 1+2 concentrations fell, whereas other markers were unchanged. CONCLUSIONS: FH exhibits an increased thrombin generation potential, an intact fibrinolysis, and has no convincing signs of inflammation. Angiotensin has proinflammatory effects, and might have minor profibrinolytic and procoagulatory effects.
Assuntos
Angiotensina II/administração & dosagem , Angiotensina II/farmacologia , Hemostasia/efeitos dos fármacos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/patologia , Inflamação/complicações , Adulto , Antifibrinolíticos/metabolismo , Biomarcadores/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Calibragem , Estudos de Casos e Controles , Demografia , Feminino , Fibrinolisina/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Leucócitos/metabolismo , Masculino , Fragmentos de Peptídeos/metabolismo , Placebos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Protrombina/metabolismoRESUMO
OBJECTIVES: Patients with familial combined hyperlipidemia (FCHL) are at increased risk of hypertension and cardiovascular disease. We examined if patients with FCHL have altered microvascular and macrovascular responses to angiotensin II, a principal mediator of the renin-angiotensin-aldosterone system. METHODS: Sixteen patients with FCHL and 16 healthy controls were investigated before, during and after a 3 h intravenous infusion of angiotensin II (10 ng/kg/min). Forearm skin microcirculation was studied by laser Doppler fluxmetry during rest and local heating to 44 degrees C (microvascular hyperemia). RESULTS: Baseline systolic blood pressures were 129 +/- 13 and 123 +/- 12 mmHg in FCHL patients and controls (P = 0.11), respectively. Angiotensin II elicited a greater systolic blood pressure response in the FCHL group (+32 +/- 13 mmHg) than in the control group (+20 +/- 11 mmHg; P < 0.001). At 3 h angiotensin II infusion, microvascular hyperemia increased in the controls (P < 0.001), whereas microvascular hyperemia was unchanged in the FCHL patients (P < 0.01, between groups). CONCLUSION: In healthy individuals, a 3 h intravenous infusion of angiotensin II enhances heat-induced microvascular hyperemia. In FCHL, this microvascular hyperemia is impaired and the systolic blood pressure response is increased. A reduced microvascular dilatation capacity in FCHL may contribute to the observed blood pressure elevation and promote development of micro- and macrovascular complications.
Assuntos
Angiotensina II/metabolismo , Hemodinâmica , Hiperlipidemia Familiar Combinada/metabolismo , Pele/irrigação sanguínea , Adulto , Angiotensina II/administração & dosagem , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Frequência Cardíaca , Temperatura Alta , Humanos , Hiperemia/metabolismo , Hiperemia/fisiopatologia , Hiperlipidemia Familiar Combinada/fisiopatologia , Infusões Intravenosas , Fluxometria por Laser-Doppler , Masculino , Microcirculação/metabolismo , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Fluxo Sanguíneo Regional , Temperatura Cutânea , Fatores de Tempo , Resistência Vascular , VasodilataçãoRESUMO
Antihypertensive treatment reduces the risk of thromboembolic events in hypertension. The aim of this study was to examine the influence of angiotensin-converting enzyme inhibition on blood coagulation in subjects with mild-to-moderate essential hypertension. Fibrinogen, thrombin-antithrombin complex (TAT) and Factor VII were determined in plasma at rest and after a mental stress test following placebo for 6 weeks, or ramipril for 6 weeks or 6 months. Ramipril reduced resting TAT, and tended to reduce fibrinogen; Factor VII remained unchanged. Mental stress increased fibrinogen, but did not alter TAT or Factor VII activity. The reduced thrombin generation in patients taking ramipril may explain in part why angiotensin-converting enzyme inhibitors reduce thromboembolic complications in patients with cardiovascular disease.