Baroreflex Amplification and Carotid Body Modulation for the Treatment of Resistant Hypertension

PURPOSE OF REVIEW: Patients with true resistant hypertension (RH) are characterized by having high sympathetic activity and therefore potentially benefit from treatments such as baroreflex amplification (baroreflex activation therapy (BAT) or endovascular baroreflex amplification therapy (EVBA)) or carotid body (CB) modulation. This review aims at providing an up-to-date overview of the available evidence regarding these two therapies. RECENT FINDINGS: In recent years, increasing evidence has confirmed the potential of baroreflex amplification, either electrically (Barostim neo) or mechanically (MobiusHD), to improve blood pressure control on short- and long-term with only few side effects, in patients with RH. Two studies regarding unilateral CB resection did not show a significant change in blood pressure. Only limited studies regarding CB modulation showed promising results for transvenous CB ablation, but not for unilateral CB resection. Despite promising results from mostly uncontrolled studies, more evidence regarding the safety and efficacy from ongoing large randomized sham-controlled trials is needed before baroreflex amplification and CB modulation can be implemented in routine clinical practice

Drug mechanisms to help in managing resistant hypertension in obesity

Obesity is a major risk factor for the development of hypertension. Because the prevalence of obesity is increasing worldwide, the prevalence of obesity hypertension is also increasing. Importantly, hypertension in obesity is commonly complicated by dyslipidemia and type 2 diabetes mellitus and hence imposes a high cardiovascular disease risk. Furthermore, obesity is strongly associated with resistant hypertension. Activation of the sympathetic nervous system and the renin-angiotensin system, leading to renal sodium and water retention, links obesity with hypertension. There is also evidence for the release of factors by visceral adipose tissue promoting excessive aldosterone production, and a more central role of aldosterone in obesity hypertension is emerging. Randomized studies evaluating the effect of different classes of antihypertensive agents in obesity hypertension are scarce, short-lasting, and small. Considering the emerging role of aldosterone in the pathogenesis of obesity hypertension, mineralocorticoid receptor antagonism may play a more central role in the pharmacologic treatment of obesity hypertension in the near future

Identifying treatment response to antihypertensives in patients with obesity-related hypertension

Background: In patients with obesity-related hypertension (ORH), reaction to antihypertensive medication is likely influenced by patientcharacteristics. Methods: Effects of aliskiren, moxonidine and hydrochlorothiazide on 24-h blood pressure (BP) were compared to placebo. Linear mixed effect models were used to analyze the effect of patient characteristics on BP levels and treatment response. Results: Systolic BP response to aliskiren was higher in patients with a BMI &gt; 30.7 kg/m2 compared to patients with a BMI ≤ 30.7 kg/m2 (-21 mmHg versus -4 mmHg). In patients with a hsCRP &gt; 1.8 mg/L the systolic BP response to aliskiren was higher than in patients with a low hsCRP (-15 mmHg versus -7 mmHg). Hydrochlorothiazide (HCTZ) treatment effect on systolic BP was -13 mmHg when heart rate &gt; 71 beats/min compared to -3 mmHg when heart rate was ≤ 71 beats/min. Conclusion: In patients with ORH, BP response to aliskiren is positively related to BMI and hsCRP. Systolic BP response to HCTZ is positively related to heart rate and negatively to renin levels. Trial registration: NCT01138423. Registered June 4th, 2010.</p

Identifying treatment response to antihypertensives in patients with obesity-related hypertension

Background: In patients with obesity-related hypertension (ORH), reaction to antihypertensive medication is likely influenced by patientcharacteristics. Methods: Effects of aliskiren, moxonidine and hydrochlorothiazide on 24-h blood pressure (BP) were compared to placebo. Linear mixed effect models were used to analyze the effect of patient characteristics on BP levels and treatment response. Results: Systolic BP response to aliskiren was higher in patients with a BMI &gt; 30.7 kg/m2 compared to patients with a BMI ≤ 30.7 kg/m2 (-21 mmHg versus -4 mmHg). In patients with a hsCRP &gt; 1.8 mg/L the systolic BP response to aliskiren was higher than in patients with a low hsCRP (-15 mmHg versus -7 mmHg). Hydrochlorothiazide (HCTZ) treatment effect on systolic BP was -13 mmHg when heart rate &gt; 71 beats/min compared to -3 mmHg when heart rate was ≤ 71 beats/min. Conclusion: In patients with ORH, BP response to aliskiren is positively related to BMI and hsCRP. Systolic BP response to HCTZ is positively related to heart rate and negatively to renin levels. Trial registration: NCT01138423. Registered June 4th, 2010.</p

Abdominal aortic calcification: from ancient friend to modern foe

BACKGROUND: Abdominal aortic calcifications were already ubiquitous in ancient populations from all continents. Although nowadays generally considered as an innocent end stage of stabilised atherosclerotic plaques, increasing evidence suggests that arterial calcifications contribute to cardiovascular risk. In this review we address abdominal aortic calcification from an evolutionary perspective and review the literature on histology, prevalence, risk factors, clinical outcomes and pharmacological interventions of abdominal aortic calcification. DESIGN: The design of this study was based on a literature review. METHODS: Pubmed and Embase were systematically searched for articles on abdominal aortic calcification and its synonyms without language restrictions. Articles with data on histology, prevalence, risk factors clinical outcomes and/or pharmacological interventions were selected. RESULTS: Abdominal aortic calcification is highly prevalent in the general population and prevalence and extent increase with age. Prevalence and risk factors differ between males and females and different ethnicities. Risk factors include traditional cardiovascular risk factors and decreased bone mineral density. Abdominal aortic calcification is shown to contribute to arterial stiffness and is a strong predictor of cardiovascular events and mortality. Several therapies to inhibit arterial calcification have been developed and investigated in small clinical trials. CONCLUSIONS: Abdominal aortic calcification is from all eras and increasingly acknowledged as an independent contributor to cardiovascular disease. Large studies with long follow-up must be carried out to show whether inhibition of abdominal aortic calcification will further reduce cardiovascular risk

Rs964184 (APOA5-A4-C3-A1) Is Related to Elevated Plasma Triglyceride Levels, but Not to an Increased Risk for Vascular Events in Patients with Clinically Manifest Vascular Disease

Background: Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Methods: Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. Results: The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10−19), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01–0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09–0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides 27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86–1.13). Conclusion: The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients

The relation between body fat distribution, plasma concentrations of adipokines and the metabolic syndrome in patients with clinically manifest vascular disease

Introduction: We evaluated the relationship between adipokine plasma concentrations and body fat distribution and the metabolic syndrome. Methods: In a cohort of 1215 patients with clinically manifest vascular disease the relation between subcutaneous adipose tissue, visceral adipose tissue, waist circumference, body mass index and plasma concentrations of adipsin, chemerin, monocyte chemoattractant protein-1, migration inhibitory factor, nerve growth factor, resistin, plasma amyloid A1, adiponectin, leptin, plasminogen activator inhibitor-1 and hepatic growth factor were cross-sectionally assessed with linear regression and adjusted for age and gender. The relation between adipokines and the metabolic syndrome was cross-sectionally evaluated using logistic regression. An adipokine profile was developed to measure the effect of combined rather than single adipokines. Results: Adiposity was related to higher nerve growth factor, hepatic growth factor, migration inhibitory factor, leptin and adipsin and with lower chemerin, plasminogen activator inhibitor-1, resistin, plasma amyloid A1 and adiponectin. The strongest positive relations were between body mass index and adipsin (β 0.247; 95% CI 0.137–0.356) and leptin (β 0.266; 95% CI 0.207–0.324); the strongest negative relations were between body mass index and plasma amyloid A1 (β –0.266; 95% CI –0.386 to –0.146) and visceral adipose tissue and adiponectin (β –0.168; 95% CI –0.226 to –0.111). There was no relation between subcutaneous adipose tissue and adipokines. Odds for the metabolic syndrome were higher with each 1 SD higher hepatic growth factor (OR 1.21; 95% CI 1.06–1.38) and leptin (OR 1.26; 95% CI 1.10–1.45) and lower with each 1 SD higher adiponectin (OR 0.73; 95% CI 0.64–0.83) and resistin (OR 0.85; 95% CI 0.74–0.97). The adipokine profile was related to the metabolic syndrome (OR 1.03; 95% CI 1.00–1.06). Conclusion: Plasma concentrations of adipokines are related to obesity and body fat distribution. The relation between adipokine concentrations and the metabolic syndrome is independent of visceral adipose tissue