RESUMO
Out-of-office blood pressure (BP) measurement is encouraged by recent hypertension guidelines for assessing BP phenotypes. These showed acceptable reproducibility in the short term, but few data exist about long-term reproducibility, particularly for chronic kidney disease (CKD) patients. We evaluated changes of the BP phenotypes at 6 and 12 months in 280 consecutive non-dialysis CKD outpatients (186 males, age 71 ± 12 years, eGFR 38 ± 13 ml/min/1.73), without any change in drug therapy. Elevated BP is defined as office BP > 140/90 and home BP > 135/85 mmHg for defining the following BP phenotypes: sustained uncontrolled hypertension (SUCH); white-coat uncontrolled hypertension (WUCH); masked uncontrolled hypertension (MUCH); and controlled hypertension (CH). At baseline, the prevalence of the phenotypes was SUCH 36.6%, CH 30.1%, WUCH 25.4% and MUCH 7.9%, and it was similar at 6 months and 12 months. On the other hand, individual phenotype reproducibility at 12 months was poor both overall (38.0%) and across the different phenotypes (SUCH 53.9%, WUCH 32.4% and CH 32.1%, MUCH 9.1%). Patients who were not maintaining the same phenotype (non-concordant) were not distinguished by age, sex, BMI, eGFR, presence of diabetes or cardiovascular disease, or pharmacological therapy. When reproducibility of BP phenotypes both at 6 months and at 12 months was assessed, it was very low (19.6%), particularly for MUCH (0%), CH (14%) and WUCH (15.5%), while it was 31% for SUCH. In a CKD cohort, the overall prevalence of the different BP phenotypes defined by office and home BP remains constant over time. However, only 38% of patients maintained the same phenotype at 12 months, suggesting a poor reproducibility over time for the BP phenotypes.
Assuntos
Pressão Sanguínea/fisiologia , Fenótipo , Insuficiência Renal Crônica/complicações , Hipertensão do Jaleco Branco/genética , Idoso , Idoso de 80 Anos ou mais , Instituições de Assistência Ambulatorial/organização & administração , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Pressão Sanguínea/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Estatísticas não Paramétricas , Hipertensão do Jaleco Branco/fisiopatologiaRESUMO
Background: White-coat effect (WCE) confounds diagnosis and treatment of hypertension. The prevalence of white-coat hypertension is higher in Europe and Asia compared to other continents suggesting that genetic factors could play a role. Methods: To study genetic variation affecting WCE, we conducted a two-stage genome-wide association study involving 1343 Finnish subjects. For the discovery stage, we used Genetics of Drug Responsiveness in Essential Hypertension (GENRES) cohort (n = 206), providing the mean WCE values from up to four separate office/ambulatory recordings conducted on placebo. Associations with p values <1 × 10-5 were included in the replication step in three independent cohorts: Haemodynamics in Primary and Secondary Hypertension (DYNAMIC) (n = 182), Finn-Home study (n = 773) and Dietary, Lifestyle and Genetic Determinants of Obesity and Metabolic Syndrome (DILGOM) (n = 182). Results: No single nucleotide polymorphisms reached genome-wide significance for association with either systolic or diastolic WCE. However, two loci provided suggestive evidence for association. A known coronary artery disease risk locus rs2292954 in SPG7 associated with systolic WCE (discovery p value = 2.2 × 10-6, replication p value = 0.03 in Finn-Home, meta-analysis p value 2.6 × 10-4), and rs10033652 in RASGEF1B with diastolic WCE (discovery p value = 4.9 × 10-6, replication p value = 0.04 in DILGOM, meta-analysis p value = 5.0 × 10-3). Conclusion: This study provides evidence for two novel candidate genes, SPG7 and RASGEF1B, associating with WCE. Our results need to be validated in even larger studies carried out in other populations.
Assuntos
Estudo de Associação Genômica Ampla , Hipertensão do Jaleco Branco/genética , ATPases Associadas a Diversas Atividades Celulares/genética , Hipertensão Essencial/genética , Feminino , Finlândia , Humanos , Masculino , Síndrome Metabólica/genética , Metaloendopeptidases/genética , Pessoa de Meia-Idade , Obesidade/genética , Fatores ras de Troca de Nucleotídeo Guanina/genéticaRESUMO
BACKGROUND: White coat effect (WCE), the blood pressure (BP) difference between clinical and non-clinical settings, can lead to clinical problems such as misdiagnosis of hypertension. Etiology of WCE has been still unclear, especially from genetic aspects. The present article investigated association between genome-wide single nucleotide polymorphisms (SNPs) and WCE in patients with essential hypertension. METHODS: The present cross-sectional analyses were based on 295 Japanese essential hypertensive outpatients aged â§40 years enrolled in randomized control study, Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP) study, who were not taking antihypertensive medications before the randomization. Home and clinic BP were measured. WCE was defined by subtracting home BP from clinic BP. Genotyping was conducted with 500K DNA microarray chips. Association between genome-wide SNPs and WCE were analyzed. For replication (p < 10-4), we analyzed participants from Ohasama study who took no antihypertension medications and whose SNPs were collected. RESULTS: Genome-wide SNPs were not significantly associated with WCE of systolic and diastolic BP after corrections of multiple comparisons (p < 2 × 10-7). We found suggestive SNPs associated with WCE of systolic and diastolic BP (p < 10-4). However, the consistent results were not obtained in the replication study. CONCLUSION: The present article showed no significant association between genome-wide SNPs and WCE. Since there were several suggestive SNPs associated with WCE, the present study warrants a further study with bigger sample size for investigating the genetic influence on WCE.
Assuntos
Pressão Sanguínea/genética , Hipertensão Essencial/genética , Hipertensão do Jaleco Branco/genética , Idoso , Assistência Ambulatorial , Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Estudos Transversais , Hipertensão Essencial/tratamento farmacológico , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Ensaios Clínicos Controlados Aleatórios como Assunto , SístoleRESUMO
AIM: The aim of the present study was to investigate the association of circulating miRNAs with white-coat hypertension (WCH) and further analyze whether miRNAs could be as potential biomarkers for WCH. METHOD: Quantitative reverse transcriptase PCR (qRT-PCR) was used to evaluate the expression of selected miRNAs. The area under the receiver-operating characteristic curve was used to evaluate diagnostic accuracy. RESULTS: MiR-30a yielded an AUC of 0.984 (95% CI: 0.001-1.00; p < 0.001) and 0.816 (95% CI: 0.718-0.915; p < 0.001); miR-29 yielded an AUC of 0.955 (95% CI: 0.913-0.998; p < 0.001) and 0.799 (95% CI: 0.697-0.902; p < 0.001); miR-133 yielded an AUC of 0.949 (95% CI: 0.900-0.999; p < 0.001) and 0.713 (95% CI: 0.593-0.834; p < 0.001), respectively. CONCLUSION: The study suggested that miR-30a, miR-29 and miR-133 have great potential to be noninvasive screening tools for WCH detection.
Assuntos
MicroRNAs/sangue , Hipertensão do Jaleco Branco/diagnóstico , Idoso , Área Sob a Curva , Biomarcadores/sangue , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Hipertensão do Jaleco Branco/genética , Hipertensão do Jaleco Branco/metabolismoRESUMO
BACKGROUND: Blood pressure (BP) is known to aggregate in families. Yet, heritability estimates are population-specific and no Swiss data have been published so far. We estimated the heritability of ambulatory and office BP in a Swiss population-based sample. METHODS: The Swiss Kidney Project on Genes in Hypertension is a population-based family study focusing on BP genetics. Office and ambulatory BP were measured in 1009 individuals from 271 nuclear families. Heritability was estimated for SBP, DBP, and pulse pressure using a maximum likelihood method implanted in the Statistical Analysis in Genetic Epidemiology software. RESULTS: The 518 women and 491 men included in this analysis had a mean (±SD) age of 48.3 (±17.4) and 47.3 (±17.7) years, and a mean BMI of 23.8 (±4.2) and 25.9 (±4.1) kg/m, respectively. Narrow-sense heritability estimates (±standard error) for ambulatory SBP, DBP, and pulse pressure were 0.37â±â0.07, 0.26â±â0.07, and 0.29â±â0.07 for 24-h BP; 0.39â±â0.07, 0.28â±â0.07, and 0.27â±â0.07 for day BP; and 0.25â±â0.07, 0.20â±â0.07, and 0.30â±â0.07 for night BP, respectively (all Pâ<â0.001). Heritability estimates for office SBP, DBP, and pulse pressure were 0.21â±â0.08, 0.25â±â0.08, and 0.18â±â0.07 (all Pâ<â0.01). CONCLUSIONS: We found significant heritability estimates for both ambulatory and office BP in this Swiss population-based study. Our findings justify the ongoing search for the genetic determinants of BP.
Assuntos
Pressão Sanguínea/genética , Hipertensão , Adulto , Determinação da Pressão Arterial , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Suíça/epidemiologia , Hipertensão do Jaleco Branco/epidemiologia , Hipertensão do Jaleco Branco/genéticaRESUMO
Resistant hypertension (RH), defined simply, is blood pressure (BP) requiring the use of four or more antihypertensive agents, whether controlled or uncontrolled. RH is an increasingly common problem in elderly patients and may affect as many as 20% of the hypertensive population. Unfortunately, at least 30% of patients evaluated for RH are actually adequately controlled when more carefully assessed by home BP monitoring or ambulatory BP monitoring, thus representing a white coat effect. It is also essential to exclude pseudoresistance resulting from improper BP recording techniques or failure of the patient to adhere to the prescribed treatment regimen. Concurrent use of drugs that may interfere with prescribed antihypertensive agents, including many over the counter herbal preparations, must also be excluded. The underlying mechanisms principally driving true RH include pathophysiologic abnormalities of aldosterone signaling, sodium and water retention, excessive sympathetic nervous system activity, and obstructive sleep apnea. Appropriate treatment regimens will usually include an inhibitor of the renin-angiotensin-aldosterone system, a calcium channel blocker, and a diuretic. An aldosterone receptor blocker can be instituted at any step, and is very effective as a fourth drug. Beta-blockers can also be integrated into these treatment plans and may be especially helpful when excessive sympathetic nervous system activity is suspected. Novel device therapies that interrupt sympathetic nerve stimulation at the carotid sinus and kidney are under investigation, and may add entirely new directions in the management of RH. What is most important is that treatment regimens should be targeted to specific patient profiles.