Risk Factor For Resistant Hypertension Research Articles

Are lead, cadmium and mercury risk factors for resistant hypertension?

BackgroundLead (Pb), cadmium (Cd) and mercury (Hg) are toxic trace elements that represent a public health problem as risk factors for cardiovascular disease and hypertension (HT) and could also contribute to the development of resistant hypertension (rHT) AimsTo compare the blood concentrations of Pb, Cd and Hg in subjects with resistant and non-resistant HT and to define whether there is a relationship between its levels and rHT. MethodsCross-sectional study. Subjects aged ≥ 21 to ≤ 80 years with a body mass index < 40 kg/m2 were recruited on a discretionary basis from October 2001 to October 2004 in a hypertension unit of a tertiary hospital amongst those sent to the hypertension unit by their family physician. Resistant hypertension was defined according to the American Heart Association (AHA) criteria. Whole blood concentrations of Cd, Pb and Hg were measured by electrothermal atomic absorption spectrometry. Results46 out of 73 included subjects (63%) suffered from rHT. Blood Pb median: HT 3.9 (IQR 2.7–5.2) vs. rHT 3.6 (IQR 2.8–6.0) µg/dL (p=0.941). Blood Cd median: HT 0.07 (IQR 0.07–0.80) vs. rHT 0.30 (IQR 0.07–0.65) µg/L (p=0.681). Blood Hg median: HT 7.9 (IQR 5.8–12.9) vs. rHT 7.3 (IQR 4.6–13.3) µg/L (p=0.611). Considering the 75th percentile of each element (Pb: 5.55 µg/dL, Cd: 0.75 µg/L, Hg: 13.15 µg/L), a multiple logistic regression analysis (adjusted for age, BMI, diabetes mellitus, clearance of creatinine and only for Cd the smoking habit) showed an OR = 3.44 (0.84–14.10, p=0.086) for Pb, OR = 1.80 (0.39–8.24, p=0.451), for Cd and OR = 2.31 (0.59–9.14, p=0.232) for Hg. Moreover, the stratified analyses showed that men with Pb ≥5.55 µg/dL have a 14 times higher risk of suffering from rHT (p=0.026). Interestingly, a 9-fold increased risk was found for non-obese subjects with elevated Pb levels, above 5.55 µg/dL (p=0.029). Also in men, the probability of suffering from rHT was more than 7 times higher if Cd levels were ≥ 0.75 µg/L (p=0.076). Most smokers had higher Cd levels, with a high risk of suffering from rHT (ORa 12.6 (0.8–200.2), p=0.072). ConclusionA higher blood Pb levels, defined by the 75th percentile (Pb ≥ 5.55 µg/dL), is associated with a greater risk of suffering from rHT and to a lesser extent in the case of Cd and Hg.

Prevalence and Risk Factors for Resistant Hypertension: Cross-Sectional Study From a Tertiary Care Referral Hospital in South India.

BackgroundAround 10% patients with hypertension have resistant hypertension (RH). Older age, Black race, obesity, diabetes mellitus (DM) and chronic kidney disease (CKD) are the common risk factors for RH. The present study was done to find out the prevalence and factors associated with RH.MethodsThis cross-sectional study was done between December 2018 and February 2020. Adult patients registered with the hypertension clinic and on care for more than three months were included in the study. History was noted and blood pressure (BP) was measured using standard precautions. The patients were divided into two groups - resistant and non-resistant hypertension. Chi-square test was done to check the significance of the differences between the two groups. Binary logistic regression was done for the risk factors with a p-value < 0.2 in the Chi-square test.ResultsA total of 275 patients were included. The mean age was 56 ± 10 years and 61% were females. The mean duration of hypertension was 7 ± 5 years; 77% of patients were overweight or obese. A family history of hypertension was present in 30% and 18% had diabetes mellitus. History suggestive of secondary hypertension was present in 13%. BP was controlled (<130/80 mm of hg) in 145 (53%), uncontrolled in 130 (47%) and resistant hypertension was seen in 31 [(11%) 95% CI 8-16%] patients. Duration of hypertension, obesity, and elevated fasting blood sugar were significantly associated with RH. ConclusionsRH was found in 11% of hypertensive patients. Longer duration of hypertension, obesity, and higher fasting blood glucose were associated with RH.

Impaired l-arginine-nitric oxide pathway contributes to the pathogenesis of resistant hypertension.

The precise mechanisms underlying resistant hypertension remain elusive. Reduced nitric oxide (NO) bioavailability is frequently documented in chronic kidney disease, obesity, diabetes and advanced age, all of which are risk factors for resistant hypertension. Sympathetic overactivity and chronic activation of the renin-angiotensin system are salient features of resistant hypertension. Interestingly, recent data indicate that renal sympathetic overactivity can reduce the expression of neuronal nitric oxide synthase in the paraventricular nucleus. Reduced NO levels in the paraventricular nucleus can increase sympathetic outflow and this can create a vicious cycle contributing to resistant hypertension. Angiotensin II can reduce l-arginine transport and hence NO production. Reduced NO levels may reduce the formation of angiotensin 1-7 dampening the cardio-protective effects of the renin-angiotensin system contributing to resistant hypertension. In addition, interleukin-6 (IL-6) is demonstrated to be independently associated with resistant hypertension, and IL-6 can reduce NO synthesis. Despite this, NO levels have not been quantified in resistant hypertension. Findings from a small proof of concept study indicate that NO donors can reduce blood pressure in patients with resistant hypertension but more studies are required to validate these preliminary findings. In the present paper, we put forward the hypothesis that reduced NO bioavailability contributes substantially to the development of resistant hypertension.

Low-Level Cumulative Lead and Resistant Hypertension: A Prospective Study of Men Participating in the Veterans Affairs Normative Aging Study.

BackgroundBone lead offers a better method over blood lead measurement to discern long‐term lead exposure and accumulation. We examined the risk of resistant hypertension based on bone lead levels in a prospective cohort study of NAS (Normative Aging Study).Methods and ResultsParticipants had clinic data on hypertension (systolic blood pressure, diastolic blood pressure, and antihypertension medication), lead (blood, bone‐patella, bone‐tibia), and demographic and confounding variables. Cases of resistant hypertension were identified by meeting criteria for: (1) inadequate systolic blood pressure (>140 mm Hg) or diastolic blood pressure (>90 mm Hg) while taking 3 medications or (2) requiring >4 medications for blood pressure control. A modified Poisson regression was used for model analysis. Of the 475 participants, 97 cases of resistant hypertension (20.4%) were identified. Among the cases of resistant hypertension, the median tibia and patella lead levels were 20 μg/g and 25 μg/g, respectively, while median tibia and patella lead levels were 20 μg/g and 27.5 μg/g, respectively, in participants without resistant hypertension. Tibia lead demonstrated a significant association with resistant hypertension (relative risk, 1.19; 95% confidence interval, 1.01–1.41 [P=0.04]) per interquartile range increase in tibia lead (13–28.5 μg/g). Patella lead was not associated with resistant hypertension (relative risk, 1.10; 95% confidence interval, 0.92–1.31 [P=0.31]) per interquartile range increase in patella lead (18–40 μg/g). Blood lead levels were not significantly associated with resistant hypertension (relative risk, 1.11; 95% confidence interval, 0.88–1.40 [P=0.38]).ConclusionsTibia lead represents a novel risk factor for resistant hypertension. Our study demonstrates an increased association between tibia lead and resistant hypertension status, with an increased risk of 19% per 1 interquartile range increase in tibia lead.

The role of the Nox4-derived ROS-mediated RhoA/Rho kinase pathway in rat hypertension induced by chronic intermittent hypoxia.

Obstructive sleep apnea syndrome, which is a risk factor for resistant hypertension, is characterized by chronic intermittent hypoxia (CIH) and is associated with many cardiovascular diseases. CIH elicits systemic oxidative stress and sympathetic hyperactivity, which lead to hypertension. Rho kinases (ROCKs) are considered to be major effectors of the small GTPase RhoA and have been extensively studied in the cardiovascular field. Upregulation of the RhoA/ROCK signaling cascade is observed in various cardiovascular disorders, such as atherosclerosis, pulmonary hypertension, and stroke. However, the exact molecular function of RhoA/ROCK in CIH remains unclear and requires further study. This study aimed to investigate the role of the NADPH oxidase 4 (Nox4)-induced ROS/RhoA/ROCK pathway in CIH-induced hypertension in rats. Male Sprague-Dawley rats were exposed to CIH for 21days (intermittent hypoxia of 21% O2 for 60s and 5% O2 for 30s, cyclically repeated for 8h/day). We randomly assigned 56 male rats to groups of normoxia (RA) or vertically implemented CIH together with vehicle (CIH-V), GKT137831 (CIH-G), N-acetyl cysteine (NAC) (CIH-N), or Y27632 (CIH-Y). The rats in the RA group were continuously exposed to room air, whereas the rats in the other groups were exposed to CIH. Systolic blood pressure (BP) was monitored at the beginning of each week. After the experiment, renal sympathetic nerve activity (RSNA) was recorded, and serum and renal tissues were subjected to molecular biological and biochemical analyses. Compared with the BP of RA rats, the BP of CIH-V rats started to increase 2weeks after the beginning of the experiment, subsequently stabilizing at a high level at the end of the third week. CIH increased both RSNA and oxidative stress. This response was attenuated by treatment of the rats with GKT137831 or NAC. Inhibiting Nox4 activity or ROS production reduced RhoA/ROCK expression. Treatment with Y27632 reduced both BP and RSNA in rats exposed to CIH. Hypertension can be induced by CIH in SD rats. The CIH-induced elevation of BP is at least partially mediated via the Nox4-induced ROS/RhoA/ROCK pathway.

Asymptomatic hyperuricemia is a strong risk factor for resistant hypertension in elderly subjects from general population.

In clinical practice, patient characteristics predicting resistant hypertension (RH) include higher blood pressure levels, left ventricular hypertrophy, older age, obesity, chronic kidney disease and diabetes. On the contrary little is known about the role of serum uric acid (SUA) as a risk factor for RH in subjects from general population. 580 elderly subjects aged ≥65 years were enrolled in the Risk Of Vascular complications Impact of Genetics in Old people (ROVIGO) study. RH was defined as the failure to maintain blood pressure values below 140mmHg (systolic) and 90mmHg (diastolic) despite therapeutic interventions that include appropriate lifestyle measures plus adherence to treatment with full doses of at least three antihypertensive drugs, including a diuretic. RH was confirmed using 24-h ambulatory blood pressure measurement. Hyperuricemic was defined as the subjects having SUA ≥6.8mg/dl or taking uricosuric drugs. Gender-specific odds ratio (OR) for RH was calculated by logistic regression analysis. The prevalence of RH was 5.7% in the cohort and was higher in women (8.3%) than in men (3.0%, p<0.05). Independent of chronic kidney disease (OR 3.89, 95% confidence interval 1.49-10.1), hyperuricemia predicted resistant hypertension in women (odds ratio 3.11, 95% confidence intervals 1.06-9.1, p=0.03) but not in men. In elderly women from the general population, an SUA value of ≥6.8mg/dl triples the risk of RH. SUA assessment should be recommended to better define the pattern of risk associated with RH.

The highly neglected burden of resistant hypertension in Africa: a systematic review and meta-analysis

ObjectiveThe hypertension epidemic in Africa collectively with very low rates of blood pressure control may predict an incremented prevalence of resistant hypertension (RH) across the continent. The aim of this study was to determine the prevalence of RH and associated risk factors in Africa.Data sourcesWe conducted a comprehensive search of electronic databases (PubMed, EMBASE, Africa Wide Information and Africa Index Medicus) completed by manual search of articles, regardless of language or publication date.MethodsWe included studies which have reported the prevalence and/or risk factors for RH in Africa from inception to 19 May 2016. Forest plots were drawn to visualise the combined prevalence of RH and extent of statistical heterogeneity between studies.ResultsOut of 259 retrieved studies, only 5 from Cameroon, Nigeria, Burkina Faso, Lesotho and Algeria with a total population of 4 068 patients were finally included in this review. There was no study from the Eastern part of Africa. Though the definition of RH was not similar across studies, its prevalence was respectively 11.7%, 4.9%, 14.6%, 14.3% and 19.0%, with an overall pooled prevalence of 12.1% (95% CI 8.0% to 17.7%). Potential risk factors were: non-compliance to treatment, ageing, male sex, dyslipidaemia, metabolic syndrome, previous cardiovascular events, physical inactivity and stress, but not excessive salt intake, alcohol and coffee ingestions. Moreover, diabetes, smoking, obesity and renal insufficiency yielded discrepant results.ConclusionsThere is a huge dearth of research on the epidemiology of RH in Africa. Thereby, an extensive study of RH prevalence and risk factors is still largely warranted to curtail the high and continuously increasing burden of hypertension across Africa.

Effects of Dietary l-Arginine on Nitric Oxide Bioavailability in Obese Normotensive and Obese Hypertensive Subjects.

Obesity related hypertension is a major risk factor for resistant hypertension. We do not completely understand the mechanism(s) underlying the development of obesity related hypertension which hinders the development of novel treatment strategies for this condition. Data from experimental studies and small clinical trials indicate that transport of l-arginine, the substrate for nitric oxide (NO), and subsequent NO production are reduced in obesity induced hypertension. Reduced NO bioavailability can induce hypertension via multiple mechanisms. Mirmiran et al. recently analyzed data from a large population study and found that the association between dietary l-arginine and serum nitrate and nitrite was weakened in obese hypertensive subjects compared to obese normotensives. These data suggest that l-arginine dependent NO production is impaired in the former group compared to the latter which may represent a novel mechanism contributing to hypertension in the setting of obesity.

PP.41.24

Objective: It's well established that resistant hypertension (RH) is associated with a longer history of hypertension, obesity and other accompanying cardiovascular (CV) risk factors, such as diabetes, left ventricular hypertrophy (LVH), albuminuria and chronic renal dysfunction (CKD). On the contrary little is known about the role of serum uric acid (SUA) as risk factor for RH. Design and method: The Risk Of Vascular complications: Impact of Genetics in Old people (ROVIGO) study is a cross-sectional, population-based study performed in 580 elderly subjects aged >= 65 years, representative of general population living in Rovigo, a town of Veneto region, in the North-Eastern of Italy. According to 2013 ESH/ESC guidelines RH was defined as failure to lower clinic systolic and diastolic blood pressure (BP) values <140/90 mmHg despite a therapeutic strategy including appropriate lifestyle measures plus the adherence to treatment with full doses of at least 3 antihypertensive drugs, including a diuretic. We defines hyper-uricemic subjects, those having SUA level >= 6.5 mg/dl, this latter a cut-off value for which in physiologic conditions SUA precipitation is observed. LVH was diagnosed by 12-leads electrocardiogram using the Sokolow-Lion index criterion and CKD was defined by an eGFR<60 ml/min/1.73m2 calculated with the MDRD formula. Gender specific odds ratio (OR) and 95% confidence intervals (CI 95%) for RH were calculated for independent variables by binary logistic regression analysis. Results: The prevalence of RH was 5.7% and it was not different in men than in women (6.3% and 5.2%, NS, respectively). Independently of age, history oh hypertension, anti-hypertensive treatment, diabetes, obesity (i.e. BMI>30 kg/m2), LVH, albuminuria, and CKD, hyper-uricemia predicts RH in women (OR 4.4, CI95% 1.24–15.7, p = 0,022) but not in men (OR 1.46, CI95% 0.51 -4.21, p = 0.47). Conclusions: In elderly women from general population a SUA > = 6.5 mg/dl 4-fold increase the risk of RH. To better define the REAL burden of RH, SUA assessment is recommended. We speculate that lowering SUA levels may reduce the prevalence of RH. However to confirm this hypothesis interventional clinical trials are needed.

Intensive blood pressure control during the hyperacute phase of intracerebral hemorrhage in patients at risk for resistant hypertension: A retrospective cohort study

IntroductionThere are limited data evaluating intensive systolic blood pressure (SBP) control during the hyperacute phase of intracerebral hemorrhage (ICH) in patients with multiple risk factors for resistant hypertension. We evaluated the feasibility and safety of this intervention in a primary population that includes patients with multiple risk factors for resistant hypertension. Materials and methodsWe conducted a retrospective analysis of ICH patients for which intensive SBP control (<140 mm Hg)- i.e. less than or equal to 140 was targeted. All patients possessed at least 2 risk factors that have been associated with resistant hypertension. Our primary objective was to determine the percentage of patients who achieved goal SBP within 1 hour of ICH diagnosis. Secondary objectives included identifying predictors of achieving goal SBP within 6 hours. ResultsGoal SBP within 1 hour was achieved in 8.1% of patients. The total number of risk factors a patient possessed was found to negatively predict ability to achieve goal SBP. For each risk factor possessed, the odds of achieving goal SBP within 6 hours are reduced by 31% (odds ratio, 0.69 [95% confidence interval, 0.54-0.89]). ConclusionIntensive SBP control after ICH was difficult to achieve within 1 hour in those with risk factors for resistant hypertension. Patients' total risk factors were found to reduce the odds of achieving goal SBP within 6 hours.

The Role of Obesity and Obstructive Sleep Apnea in the Pathogenesis and Treatment of Resistant Hypertension

The incidence of resistant hypertension, obesity, and obstructive sleep apnea (OSA), three highly prevalent conditions in the United States, is rising. Approximately one in three adults in the US has hypertension, and a significant proportion of these individuals have hypertension that is difficult to treat, or resistant. Obesity and OSA are well-established risk factors for resistant hypertension, a condition that portends significant cardiovascular risk. Awareness of the various mechanisms by which obesity and OSA impact systemic blood pressure is essential to better understand how best to effectively care for patients with resistant hypertension. In this review, we discuss the clinical and pathophysiologic associations between obesity, OSA, and resistant hypertension. Furthermore, we will explore the effect of continuous positive airway pressure therapy (CPAP) and other therapeutic interventions on blood pressure control in patients with resistant hypertension.Key Points• Obesity, obstructive sleep apnea, and resistant hypertension are highly prevalent conditions, with increasing overall incidence [1-3].• Both obesity and obstructive sleep apnea are independent risk factors for the development of resistant hypertension.• OSA is characterized by a physiologic cascade of collapse of the upper airway, which can lead to intermittent hypoxia, hypercapnia, significant negative intra-thoracic pressure, and increased SNS output.• Intermittent hypoxia leads to activation of the endothelin system [17, 18, 19•], which can lead to the development of resistant hypertension.• Intermittent hypoxia can lead to the over activation of the SNS, which can also contribute to the development of resistant hypertension [20, 21].• OSA leads to state of elevated adrenergic tone, which in turn may contribute to resistant hypertension [25-27].• OSA patients have a higher incidence of "non-dipping" of nocturnal systolic blood pressure, a marker of increased adrenergic tone. This potentially represents a risk factor for hypertensive end organ disease [31, 32].• The prevalence of OSA is significantly higher in patients predisposed to fluid accumulation: including kidney disease, heart failure and resistant hypertension [33].• Interventions (such as the daytime use of compression stocking) which reduce daytime lower extremity fluid accumulation can significantly reduce the severity of OSA, particularly in patients with comorbid resistant hypertension [35, 36].• CPAP therapy can significantly reduce blood pressure in patients with comorbid hypertension and OSA. The treatment effect is most pronounced in those with resistant hypertension and OSA [16••, 38-42].

Prevalence and risk factors for resistant hypertension among hypertensive patients from a developing country

BackgroundTo study the prevalence and define deferential risk factors for ‘Resistant’ hypertension (RHT) in a hypertensive population of South Asian origin.MethodsA descriptive cross-sectional study was carried out among hypertensive patients attending clinics at the Cardiology Unit, Colombo from July-October 2009. All the patients with hypertension who provided informed written consent were recruited to the study (n = 277). A pre-tested interviewer-administered questionnaire was used for data collection. A binary logistic-regression analysis was performed in all patients with ‘presence of RHT’ as the dichotomous dependent variable and other independent co-variants.ResultsMean age was 61 ± 10.3 years and 50.2% were males. The mean of average systolic and diastolic blood pressures (BP) were 133.04 ± 12.91 mmHg and 81.07 ± 6.41 mmHg respectively. Uncontrolled BP was present in 41.1% (n = 114) of patients, of which RHT was present in 19.1% (n = 53). Uncontrolled BP were due to ‘therapeutic inertia’ in 27.8% of the study population. Those with diabetes mellitus, obesity (BMI > 27.5 kg/m2) and those who were older than 55 years were significantly higher in the RHT group than in the non-RHT group. In the binary logistic regression analysis older age (OR:1.36), longer duration of hypertension (OR:1.76), presence of diabetes mellitus (OR:1.67) and being obese (OR:1.84) were significantly associated with RHT.ConclusionA significant proportion of the hypertensive patients were having uncontrolled hypertension. Nearly 1/5th of the population was suffering from RHT, which was significantly associated with the presence of obesity and diabetes mellitus. Therapeutic inertia seems to contribute significantly towards the presence of uncontrolled BP.

Prevalence of resistant hypertension in 1810 patients followed up in a specialized outpatient clinic and its association with the metabolic syndrome

We aimed to assess the prevalence of resistant hypertension (RH) in patients attending hypertension outpatient clinics and to identify risk factors for RH. We studied the medical records of the last visit of all patients (n = 1810; 40.4% males, age 56.5 ± 13.5 years) who attended at least once our hypertension outpatient clinic during the last decade. RH was defined as blood pressure (BP) > 140/90 mmHg in patients without diabetes or chronic kidney disease (or BP > 130/80 mmHg in patients with the latter diseases) despite treatment with full doses of three antihypertensive agents from different classes or controlled BP on four or more different antihypertensive agents. The prevalence of RH was 12.3%, whereas 22.2% of the patients had well-controlled hypertension and 65.5% had uncontrolled hypertension but were on less than three antihypertensive agents. Independent predictors of RH were age (risk ratio, RR = 1.08, 95% confidence interval, CI 1.05–1.12, p < 0.001), body mass index (RR = 1.06, 95% CI 1.00–1.13, p < 0.05) and the presence of the metabolic syndrome (MetS) (RR = 2.01, 95% CI 1.03–3.91, p < 0.05). Conclusions. RH is frequent in patients followed up in hypertension outpatient clinics. In addition to age and obesity, MetS appears to be associated with increased risk for RH. Clarification of the mechanisms underpinning the association between MetS and hypertension might reduce the prevalence of RH.

Resistant Hypertension and Obstructive Sleep Apnea

Hypertension (HTN) is a modifiable, highly prevalent risk factor for cardiovascular morbidity and renal dysfunction worldwide. In the United States, HTN affects one in three adults, contributes to one out of every seven deaths and to nearly half of all cardiovascular disease-related deaths. HTN is considered resistant when the blood pressure remains above goal despite lifestyle modification and administration of three antihypertensive agents of different classes including a diuretic. Large population-based studies have suggested that obstructive sleep apnea (OSA) is a risk factor for resistant HTN. The mechanism proposed is a pattern of intermittent hypoxia associated with hyperaldosteronism, increased sympathetic tone, endothelial dysfunction, and inflammation. In this review we discuss the association between OSA and resistant HTN, the physiologic mechanisms linking OSA with resistant HTN, and the effect of continuous positive airway pressure therapy (CPAP) on blood pressure in patients with resistant HTN. While the reduction in blood pressure with CPAP is usually modest in patients with OSA, a decrease of only a few mmHg in blood pressure can significantly reduce cardiovascular risk. Patients presenting to a center specializing in management of hypertension should be screened and treated for OSA as a potentially modifiable risk factor.

Resistant hypertension and the neglected antihypertensive: sodium restriction

Resistant hypertension is defined as blood pressure (BP) that remains above goal (such as 140/90 mmHg or more) in spite of the concurrent use of three antihypertensive agents of different classes. Ideally, one of the three agents should be a diuretic and all agents should be prescribed at optimal dose amounts. Prevalent among 15% of the treated hypertensives, the risk factors for resistant hypertension include older age, chronic kidney disease (CKD), obesity and diabetes mellitus. Causes of resistant hypertension can be classified into four groups: poor adherence, biological-behavioral factors, CKD and secondary causes, and drugs or exogenous substances. However, before labeling the diagnosis of resistant hypertension, it is important to exclude pseudo-resistant hypertension using home BP monitoring in most patients and ambulatory BP monitoring in a few. Before thinking about the next antihypertensive drug, it is important to restrict dietary sodium. Educating the patient on how to interpret the food label and providing feedback by assessing sodium intake with 24 h urine collection are effective sodium restriction strategies. Sodium restriction can lower BP and among patients with proteinuria can even enhance the anti-proteinuric effects of drugs that block the renin-angiotensin system. Sodium restriction is therefore a valuable but a neglected antihypertensive.

Gene Variation in Resistant Hypertension: Multilocus Analysis of the Angiotensin 1-Converting Enzyme, Angiotensinogen, and Endothelial Nitric Oxide Synthase Genes

Resistant hypertension, a complex multifactorial hypertensive disease, is triggered by genetic and environmental factors and involves multiple physiological pathways. Single genetic variants may not reveal significant associations with resistant hypertension because their effects may be dependent on gene-gene or gene-environment interactions. We examined the interaction of angiotensin I-converting enzyme (ACE), angiotensinogen (AGT), and endothelial nitric oxide synthase (NOS3) polymorphisms with environmental factors (gender, age, body mass index, glycemia, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate, and urinary sodium excretion) in 70 resistant, 80 well-controlled hypertensive patients, and 70 normotensive controls. All subjects were genotyped for ACE insertion/deletion (rs1799752); AGT M235T (rs699), and NOS3 Glu298Asp (rs 1799983). Multifactorial associations were tested using two statistical methods: the traditional parametric method (adjusted logistic regression analysis) and gene-gene and gene-environment interactions evaluated by multifactor dimensionality reduction analyses. While adjusted logistic regression found no significant association between the studied polymorphisms and controlled or resistant hypertension, the multifactor dimensionality reduction analyses showed that carriers of the AGT 235T allele were at increased risk for resistant hypertension, especially if they were older than 50 years. The AGT 235T allele constituted an independent risk factor for resistant hypertension.

Risk for Obstructive Sleep Apnea by Berlin Questionnaire, But Not Daytime Sleepiness, Is Associated With Resistant Hypertension: A Case-control Study

Obstructive Sleep Apnea Syndrome (OSAS) is a risk factor for resistant hypertension. Overnight polysomnography and portable sleep monitors are not generally available and questionnaires may be useful for screening OSAS. In a case-control study, we investigate the association between resistant hypertension and sleep disorders evaluated by the Berlin Questionnaire and Epworth Sleepiness Scale (ESS). Cases were 63 patients with resistant hypertension (either systolic blood pressure (BP) > or =140 mm Hg or diastolic BP > or =90 mm Hg using at least three BP-lowering drugs, including a diuretic). Controls were 63 patients with controlled BP under drug treatment. All the patients were submitted to ambulatory BP monitoring and level III polysomnography by means of a portable monitor. The prevalence of high risk in the Berlin Questionnaire and high score in the ESS (>10) was compared between the groups. Diagnostic performance for OSAS of both questionnaires was calculated. The prevalence of high score in ESS was 44% in both groups. There was a higher prevalence of high risk for OSAS in Berlin Questionnaire in the cases group (78% vs. 48%; P < 0.001). In a logistic regression model, high risk for OSAS in Berlin Questionnaire was independently associated with resistant hypertension (odds ratio 4.1; confidence interval 95% 1.80-9.31; P < 0.01). Sensitivity and specificity for the diagnosis of OSAS was 85.5% (75.3-92.0%) and 65.0% (52.0-76.0%), respectively. High risk for OSAS assessed by the Berlin Questionnaire is highly prevalent and associated with resistant hypertension. This questionnaire may be used as screening for OSAS in patients with this clinical condition.

Obstructive Sleep Apnea and Resistant Hypertension: A Case-Control Study

Obstructive sleep apnea syndrome (OSAS) has been linked to resistant hypertension, but the magnitude of this association and its independence of confounding have not been established. Case patients were 63 patients with resistant hypertension (BP >or= 140/90 mm Hg using at least three BP-lowering drugs, including a diuretic), and control subjects were 63 patients with controlled BP receiving drug treatment. The primary outcome was the frequency of OSAS (apnea-hypopnea index [AHI] >or= 10 episodes per hour) determined with a portable home monitor. The comparison of AHI episodes in patients truly normotensive, truly hypertensive, and in patients with white coat or masked hypertension, based on BP determined at office and by ambulatory BP monitoring (ABPM) was a secondary outcome. Case patients and control subjects were well matched for confounding factors. OSAS was present in 45 case patients (71%) and in 24 control subjects (38%) [p < 0.001]. In a logistic regression model, OSAS was strongly and independently associated with resistant hypertension (odds ratio, 4.8; 95% confidence interval, 2.0 to 11.7). The AHI of case patients with normal BP in ABPM (white coat hypertension) and control subjects with abnormal BP in ABPM (masked hypertension) was intermediate between the AHI of individuals with normal and abnormal BP measures in both settings (p < 0.001). The magnitude and independence of the risk of OSAS for resistant hypertension strengthen the concept that OSAS is a risk factor for resistant hypertension. Comorbid OSAS should be considered in patients with resistant hypertension.