Hypertension Cardiovascular Risk Research Articles

Circadian Rhythm and Blood Pressure: research of the latest circadian rhythm in the treatment of hypertension

The goal of this review was to synthesize present knowledge on the effect of circadian rhythms on blood pressure (BP), circadian misalignment mechanisms that contribute to hypertension, circadian rhythm, and hypertension relationship, the latest research of circadian rhythm diet and pharmacological intervention and assess the possibility of chronotherapy in treatment. BP by modulating biological function is determined by the circadian rhythm process mainly under endogenous control, including the central clock in the suprachiasmatic nucleus (SCN) and peripheral clock. Hypertension has been associated with disruption of this rhythm which is a major cardiovascular disease risk factor. A high risk for adverse cardiovascular outcomes is circadian misalignment, which is reflected mostly by nocturnal nondipping. Shift work, hormone release, dietary habits, and others that affect circadian rhythms seem implicated, according to studies. Bedtime dosing of antihypertensive medications and other forms of chronotherapy have the potential to improve BP control. Time-dependent feeding and lifestyle interventions consistent with circadian rhythms offer benefits for hypertension management, as well. Increasingly, it is recognized that circadian rhythm disruption contributes to hypertension. Because interventions that realign circadian rhythms, including chronotherapy or circadian-aligned lifestyle changes, may decrease cardiovascular risk in hypertensives, they are worthy of further study.

Salivary microbial shifting in hypertensive patients with chronic periodontitis after scaling and root surface debridement.

This study aimed to evaluate the impact of scaling and root surface debridement (SRP) on salivary bacterial counts and systolic and diastolic blood pressure in hypertensive patients with chronic periodontitis, with a focus on clinical significance. An observational trial included 24 chronic periodontitis patients, eleven of them were hypertensive patients. Non-surgical periodontal treatment was administered to all patients, with clinical parameters including gingival index (GI), plaque index (PI), and probing pocket depth (PPD) recorded. Saliva samples were collected before and after SRP to quantify total bacterial counts and specific bacterial counts. Two months following SRP, PI and PPD in every subject under study demonstrated good responses. In hypertension patients, the salivary bacterial count was significantly higher following SRP (P = 0.0221). The incidence of Porphyromonas gingivalis in hypertension patients significantly decreased after treatment (P = 0.0386). Despite this, there was no discernible decrease in blood pressure following treatment. SRP alone was ineffective in reducing overall bacterial counts, but P. gingivalis levels responded favorably. Regular periodontal assessment is crucial for hypertensive individuals to mitigate cardiovascular risk. Periodontal therapy in hypertensive patients may improve oral health but might not significantly impact blood pressure. Regular periodontal evaluation is essential for managing cardiovascular risk in hypertension.

RISK OF MAJOR ADVERSE CARDIAC EVENTS IN HYPERTENSIVE PATIENTS WITH OBSTRUCTIVE SLEEP APNEA AND METABOLIC SYNDROME: RESULTS OF A LONGITUDINAL COHORT STUDY

Objective: Obstructive sleep apnea (OSA) and metabolic syndrome (MS) may act synergistically and possibly accelerate the initiation and progression of cardiovascular events disease. We examined the joint effect of OSA and MS on the risk of major adverse cardiovascular events (MACE) in hypertensives in a Longitudinal cohort study. Design and method: We conducted a retrospective cohort study enrolling 3134 participants, no history of myocardial infarction (MI), coronary revascularization, unstable angina, and hospitalization for heart failure at baseline, from the Urumqi Research on Sleep Apnea and Hypertension study. An apnoea-hypopnoea index (AHI) of greater than or equal to 5 events per hour recorded by PSG was defined as the diagnostic criterion for OSA. MS was defined using the updated National Cholesterol Education Program Adult Treatment Panel III criteria (ATP III). The outcome was the composite of MACE, which included cardiac death, MI, coronary revascularization, unstable angina and hospitalization for heart failure. We divided participants into four groups for the primary exposure according to the presence/absence of OSA or MS. The Kaplan-Meier method helped to calculate the cumulative incidence of MACE in different groups. Cox proportional hazards regression models were used to evaluate the association of OSA and/or MS with the risk of MACE. Results: During a median follow-up period of 7.06 years (interquartile range: 6.18-8.08 years), 190 incident MACE were identified. Overall, after adjusting for confounding variables, participants with OSA and MS were associated with a 2.51-fold and 1.60-fold increased risk of MACE with corresponding HRs (95% CI) of 2.51 (1.01, 6.21) and 1.60 (1.10, 2.31), compared with participants without OSA and MS, and participants with OSA or MS, respectively. Similar results were obtained in various subgroup and sensitivity analyses. The combination of OSA and MS was associated with the highest risk of MACE among participants who in younger age, and have shorter duration of hypertension. Sensitivity analyses further validated our primary findings. Conclusions: Combination of OSA and MS in hypertension could significantly increase the risk of MACE, suggesting that recognition and treatment of OSA and MS may decrease the cardiovascular risk in hypertensives.

Effect of Medication Therapy Management by Pharmaceutical Care on Blood Pressure and Cardiovascular Risk in Hypertension: A Systematic Review, Meta-Analysis, and Meta-Regression.

Medication therapy management by pharmaceutical care (MTM-PC) has been shown to improve the effectiveness of antihypertensive treatments. The aim was to answer the question: what are the MTM-PC models and their impact on hypertensive patients' outcomes? This is a systematic review with meta-analysis. The search strategies were run on 27 September 2022 in the following databases: PubMed, EMBASE, Scopus, LILACs, Central Cochrane Library, Web of Science; and International Pharmaceutical Abstracts. The quality and bias risk was assessed by the Downs and Black instrument. Forty-one studies met the eligibility criteria and were included, Kappa = 0.86; 95% CI, 0.66-1.0; (p < 0.001). Twenty-seven studies (65.9%) had MTM-PC models outlined by the clinical team, showing as characteristics the mean of 10.0 ± 10.7 months of follow-up of hypertensive patients, with 7.7 ± 4.9 consultations. Instruments to assess the quality of life measured the enhancement by 13.4 ± 10.7% (p = 0.047). The findings of the meta-analysis show a mean reduction of -7.71 (95% CI, -10.93 to -4.48) and -3.66 (95% CI, -5.51 to -1.80), (p < 0.001) in mmHg systolic and diastolic pressures, respectively. Cardiovascular relative risk (RR) over ten years was 0.561 (95% CI, 0.422 to 0.742) and RR = 0.570 (95% CI, 0.431 to 0.750), considering homogeneous studies, I² = 0%. This study shows the prevalence of MTM-PC models outlined by the clinical team, in which there are differences according to the models in reducing blood pressure and cardiovascular risk over ten years with the improvement in quality of life.

Improving cardiovascular health in rural China and beyond

In 2021, high blood pressure claimed 11·3 million lives globally. 1 Vaduganathan M Mensah GA Turco JV Fuster V Roth GA The global burden of cardiovascular diseases and risk: a compass for future health. J Am Coll Cardiol. 2022; 80: 2361-2371 Crossref PubMed Scopus (4) Google Scholar High blood pressure has ranked consistently as the top modifiable risk factor globally for over 20 years. Although its prevalence is universally high, awareness, management, and control of high blood pressure are particularly poor in low-income and middle-income countries. 2 Geldsetzer P Manne-Goehler J Marcus ME et al. The state of hypertension care in 44 low-income and middle-income countries: a cross-sectional study of nationally representative individual-level data from 1·1 million adults. Lancet. 2019; 394: 652-662 Summary Full Text Full Text PDF PubMed Scopus (199) Google Scholar Several cluster randomised controlled trials have shown that community health worker-led interventions were effective in significantly reducing blood pressure in Argentina (the HCPIA trial), 3 He J Irazola V Mills KT et al. Effect of a community health worker-led multicomponent intervention on blood pressure control in low-income patients in Argentina: a randomized clinical trial. JAMA. 2017; 318: 1016-1025 Crossref PubMed Scopus (98) Google Scholar Malaysia and Colombia (the HOPE 4 trial), 4 Schwalm JD McCready T Lopez-Jaramillo P et al. A community-based comprehensive intervention to reduce cardiovascular risk in hypertension (HOPE 4): a cluster randomised controlled trial. Lancet. 2019; 394: 1231-1242 Summary Full Text Full Text PDF PubMed Scopus (92) Google Scholar and Bangladesh, Pakistan, and Sri Lanka (the COBRA-BPS trial). 5 Jafar TH Gandhi M de Silva HA et al. A community-based intervention for managing hypertension in rural South Asia. N Engl J Med. 2020; 382: 717-726 Crossref PubMed Scopus (68) Google Scholar More recently, in 2022, Sun and colleagues 6 Sun Y Mu J Wang DW et al. A village doctor-led multifaceted intervention for blood pressure control in rural China: an open, cluster randomised trial. Lancet. 2022; 399: 1964-1975 Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar showed that in the China Rural Hypertension Control Project (the CRHCP trial), a village doctor-led intensive hypertension intervention increased hypertension control by 37% compared with usual care. The 18-month net reduction in systolic blood pressure was as large as 14·5 mm Hg. Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention versus usual care on cardiovascular disease (CRHCP): an open-label, blinded-endpoint, cluster-randomised trialThe non-physician community health-care provider-led intensive blood pressure intervention is effective in reducing cardiovascular disease and death. Full-Text PDF

Relationship of Arterial Stiffness and Central Hemodynamics With Cardiovascular Risk In Hypertension.

Hypertension is becoming a serious public health problem and noninvasive estimation of central hemodynamics and artery stiffness have been identified as important predictors of cardiovascular disease. The study included 4,311 participants, both sex and aged between 20 and 79 years. Arterial velocity pulse index, arterial pressure-volume index (AVI, API, and the index of artery stiffness), central systolic blood pressure, central artery pulse pressure (CSBP, CAPP, and estimated via oscillometric blood pressure monitor), and 10-year risk score of cardiovascular disease in China (China-PAR) and Framingham cardiovascular risk score (FCVRS) were assessed at baseline. Regression model was performed to identify factors associated with high cardiovascular disease risk stratification. The relationships between CSBP, CAPP and China-PAR, and FCVRS were analyzed by restrictive cubic spline functions. The uncontrolled hypertension group showed the highest values of AVI, API, CSBP, and CAPP. In the regression analysis, CAPP and hypertension subtypes were identified as significant predictors of high cardiovascular risk stratification, and CAPP was strongly correlated with API in this cohort. Finally, CSBP and CAPP showed significant J-shaped relationships with China-PAR and FCVRS. Subjects with uncontrolled hypertension present with elevated values of CAPP, CSBP, API, AVI, China-PAR, and FCVRS scores. CAPP was independently associated with high cardiovascular risk stratification, and there was a significant J-shaped relationship with China-PAR and FCVRS that may identify people with higher cardiovascular risk.

Immuno-Mediated Inflammation in Hypertensive Patients with 1-h Post-Load Hyperglycemia.

Inflammation plays a key role in the pathogenesis/progression of atherosclerosis, and inflammatory molecules contribute to the progression of cardiovascular disease. Subjects with normal post-load glucose tolerance and 1-h post-load plasma glucose >155 mg/dL have an increased risk of subclinical target organ damage and incident diabetes. We aimed to test possible differences in immune-mediated inflammatory parameters in newly-diagnosed hypertensives with or without 1-h post-load hyperglycemia. We enrolled 25 normotensives (NGT) and 50 hypertensives normotolerant on oral glucose tolerance test, further divided into two groups based on 1-h post-load plasma glucose: NGT 1-h ≥ 155 (n = 25) and NGT 1-h < 155 (n = 25). We measured toll-like receptor (TLR) 2, TLR4, nuclear factor kβ (NF-kβ), interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α. Hypertensives showed significantly worse metabolic and lipid profiles, and higher values of body mass ass index (BMI), creatinine, and inflammatory parameters, compared to controls. NGT 1-h ≥ 155 had a worse glycometabolic profile and higher values of TLR2 (9.4 ± 4.2 vs. 5.9 ± 2.6 MFI), TLR4 (13.1 ± 3.9 vs. 7.8 ± 2.3 MFI), NF-kβ (0.21 ± 0.07 vs. 0.14 ± 0.04), IL-1β (6.9 ± 3.4 vs. 3.2 ± 2.1 pg/mL), IL-6 (10.8 ± 2.6 vs. 4.1 ± 1.6 pg/mL), IL-8 (27.6 ± 9.3 vs. 13.3 ± 5.6 pg/mL), TNF-α (6.4 ± 2.9 vs. 3.3 ± 1.4 pg/mL), and high-sensitivity C-reactive protein (hs-CRP) (4.8 ± 1.5 vs. 2.7 ± 1.0 mg/dL) in comparison with NGT 1-h < 155. Matsuda-index and 1-h post-load glycemia were retained as major predictors of TLRs and NF-kβ. These results contribute to better characterizing cardiovascular risk in hypertensives.

GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition.

Aberrant sympathetic nerve activity exacerbates cardiovascular risk in hypertension and diabetes, which are common comorbidities, yet clinically sympathetic nerve activity remains poorly controlled. The hypertensive diabetic state is associated with increased reflex sensitivity and tonic drive from the peripheral chemoreceptors, the cause of which is unknown. We have previously shown hypertension to be critically dependent on the carotid body (CB) input in spontaneously hypertensive rat, a model that also exhibits a number of diabetic traits. CB overstimulation by insulin and leptin has been similarly implicated in the development of increased sympathetic nerve activity in metabolic syndrome and obesity. Thus, we hypothesized that in hypertensive diabetic state (spontaneously hypertensive rat), the CB is sensitized by altered metabolic signaling causing excessive sympathetic activity levels and dysfunctional reflex regulation. Using a hypothesis-free RNA-seq approach, we investigated potential molecular targets implicated in energy metabolism mediating CB sensitization and its regulation of sympathetic outflow in experimental hypertension. Identified targets were characterized using molecular and functional techniques assessing peripheral chemoreflex sensitivity in situ and in vivo. We discovered GLP1R (glucagon-like peptide-1 receptor) expression in the CBs of rat and human and showed that its decreased expression is linked to sympathetic hyperactivity in rats with cardiometabolic disease. We demonstrate GLP1R to be localized to CB chemosensory cells, while targeted administration of GLP1R agonist to the CB lowered its basal discharge and attenuated chemoreflex-evoked blood pressure and sympathetic responses. Importantly, hyperglycemia-induced peripheral chemoreflex sensitization and associated basal sympathetic overactivity were abolished by GLP1R activation in the CB suggesting a role in a homeostatic response to high blood glucose. We show that GLP1 (glucagon-like peptide-1) modulates the peripheral chemoreflex acting on the CB, supporting this organ as a multimodal receptor. Our findings pinpoint CBs as potential targets for ameliorating excessive sympathetic activity using GLP1R agonists in the hypertensive-diabetic condition.

Эффективность амбулаторного лечения артериальной гипертензии через призму качества жизни и гемодинамический фенотип пациентов

Актуальность. Эффективность амбулаторного лечения артериальной гипертензии (АГ) как совокупный результат — достижение целевого уровня артериального давления (АДцел) и приемлемый уровень качества жизни (КЖ) пациентов, а также влияние на него гемодинамического фенотипа, определяемого оригинальным методом количественного анализа связей параметров артериального давления (КАСПАД), не исследованы, что явилось целью данной работы. Материалы и методы. Обследованы 175 амбулаторных пациентов с АГ, средний возраст 60,0 (52,0–70,0) года, получавших длительную (3–12 лет) стандартную терапию антигипертензивными препаратами из основных групп лекарственных средств (ЛС). Оценивалось КЖ по русскоязычной версии опросника RAND-36; для определения гемодинамического фенотипа по КАСПАД использованы индивидуальные ряды величин АД (не менее 25), полученные при ежедневных домашних измерениях за 2–4 недели; проведен статистический анализ клинических и демографических признаков, их связей с КЖ и фенотипами. Результаты. Значимое ухудшение КЖ (физический компонент и общий уровень) отмечено с увеличением возраста, степени и кардиоваскулярного риска АГ, особенно при наличии хронических форм ишемической болезни сердца. КЖ у пациентов, не достигших АДцел, значимо ниже по большинству параметров, чем у достигших его лиц. Увеличение количества принимаемых ЛС сопряжено со снижением КЖ у лиц, достигших АДцел. Пациенты с гемодинамическим фенотипом D, независимо от фармакологической группы принимаемых ЛС и их количества, значимо реже достигают АДцел по сравнению с лицами с фенотипом H, а также имеют более низкое КЖ, еще более снижающееся при интенсификации медикаментозной терапии. Ингибиторы ангиотензинпревращающего фермента (ИАПФ) и блокаторы кальциевых каналов (БКК) были эффективны для достижения АДцел, в основном у пациентов с фенотипом H, но негативно влияли на КЖ: ИАПФ — при фенотипе H, БКК — при D. Бета-адреноблокаторы и диуретики существенно не влияли на КЖ. Предложена статистическая модель прогноза низкого общего уровня КЖ у пациентов с достигнутым АДцел на основе 5 клинико-демографических факторов. Выводы. Эффективность лечения АГ целесообразно оценивать по совокупности достижения АДцел и общего уровня КЖ не менее 60 баллов (по RAND-36). При назначении лечения следует учитывать гемодинамический фенотип: медикаментозную терапию всех пациентов с фенотипом D, а также лиц с фенотипом H при низком КЖ и недостигнутом АДцел необходимо дополнять комплексной реабилитацией с использованием немедикаментозных методов.

Homoarginine as a laboratory cardiovascular risk biomarker

Background. Low plasma concentration of L-homoarginine (hArg) is associated with the progression of cardiovascular disease. However, the association between plasma hArg and cardiovascular complications in hypertension is not established. Objective. To assess and compare hArg levels as a biomarker of cardiovascular risk in hypertension. Design and methods. We included 60 hypertensives with moderate (n = 12), high (n = 16) and very high (n = 32) cardiovascular risk. Blood plasma tests including hArg were assessed. The control group included 30 age-matched regular donors. Results. The level of hArg was significantly lower in hypertensives compared to ocontrols (р &lt; 0,001). There were negative correlations between hArg and echocardiography parameters of left ventricular hypertrophy. In the higher cardiovascular risk groups hArg was lower (р = 0,042). ROC-analysis showed AUC 0,860 (95 % confidence interval 0,787–0,933) with the threshold for hArg ≤ 1,69 µM, sensitivity 72,0 % and specificity 93,3 %. Conclusion. The hArg plasma level is associated with the expression and enzyme activity of the protein arginine: glycinamidinetransferase in various tissues. The hArg level ≤ 1,69 µM can be considered a cumulative laboratory biomarker of high cardiovascular risk. Further studies of prognostic and diagnostic role of hArg are needed.

Arterial Stiffness and Cardiovascular Risk in Hypertension.

Arterial stiffness, a leading marker of risk in hypertension, can be measured at material or structural levels, with the latter combining effects of the geometry and composition of the wall, including intramural organization. Numerous studies have shown that structural stiffness predicts outcomes in models that adjust for conventional risk factors. Elastic arteries, nearer to the heart, are most sensitive to effects of blood pressure and age, major determinants of stiffness. Stiffness is usually considered as an index of vascular aging, wherein individuals excessively affected by risk factor exposure represent early vascular aging, whereas those resistant to risk factors represent supernormal vascular aging. Stiffness affects the function of the brain and kidneys by increasing pulsatile loads within their microvascular beds, and the heart by increasing left ventricular systolic load; excessive pressure pulsatility also decreases diastolic pressure, necessary for coronary perfusion. Stiffness promotes inward remodeling of small arteries, which increases resistance, blood pressure, and in turn, central artery stiffness, thus creating an insidious feedback loop. Chronic antihypertensive treatments can reduce stiffness beyond passive reductions due to decreased blood pressure. Preventive drugs, such as lipid-lowering drugs and antidiabetic drugs, have additional effects on stiffness, independent of pressure. Newer anti-inflammatory drugs also have blood pressure independent effects. Reduction of stiffness is expected to confer benefit beyond the lowering of pressure, although this hypothesis is not yet proven. We summarize different steps for making arterial stiffness measurement a keystone in hypertension management and cardiovascular prevention as a whole.

Elevated heart rate and cardiovascular risk in hypertension.

Epidemiological studies have shown that chronically elevated resting heart rate (HR) is significantly associated with organ damage, morbidity and mortality in a wide range of patients including hypertensive patients. Evidence is also available that an increased HR reflects sympathetic nervous system overdrive which is also known to adversely affect organ structure and function and to increase the risk of unfavourable outcomes in several diseases. The causal relationship between elevated HR, organ damage, and cardiovascular outcomes can thus be explained by its relationship with sympathetic cardiovascular influences although evidence of sympathetically-independent adverse effect of HR increases per se makes it more complex. Interventions that target HR by modulating the sympathetic nervous system have therefore a strong pathophysiological and clinical rationale. As most clinical guidelines now recommend the use of combination therapies in patients with hypertension, it might be desirable to consider as combination components drugs which lower HR, if HR is elevated such as, according to guideliines, when it is above 80 b/min.

Left ventricular myocardial oxygen demand and subclinical dysfunction in patients with severe obesity referred for bariatric surgery

Background and aimsIncreased myocardial oxygen (O2) demand carries higher cardiovascular risk in hypertension. We hypothesized that myocardial O2 demand is increased in severe obesity and linked to early left ventricular (LV) dysfunction. Methods and resultsBaseline data from 106 severely obese subjects referred for gastric bypass surgery (42 ± 11 years, 74% women, body mass index [BMI] 41.9 ± 4.8 kg/m2, 32% with hypertension) in the prospective FatWest (Bariatric Surgery on the West Coast of Norway) study was used. LV systolic function was assessed by biplane ejection fraction (EF), midwall shortening (MWS) and endocardial global longitudinal strain (GLS), and LV diastolic function by mitral annular early diastolic velocity (e’). Myocardial O2 demand was estimated from the LV mass-wall stress-heart rate product (high if > 1.62 × 106/2.29 × 106 g kdyne/cm2 bpm in women/men). High myocardial O2 demand was found in 33% and associated with higher BMI and high prevalence of low GLS (65%) and low MWS (63%) despite normal EF. In ROC analyses, higher myocardial O2 demand discriminated between patients with low vs. normal MWS and GLS (area under curve 0.71 and 0.63, p < 0.05). In successive multiple regression analyses, higher myocardial O2 demand was associated with lower LV MWS, GLS and average e’, respectively, independent of age, gender, BMI, pulse pressure, diabetes mellitus, and EF (all p < 0.05). ConclusionIn obese patients without known heart disease and with normal EF referred for bariatric surgery, high myocardial O2 demand is associated with lower myocardial function whether assessed by GLS or MWS independent of confounders. Clinicaltrials.gov identifierNCT01533142;

Cardiovascular Effects of Pharmacological Targeting of Sphingosine Kinase 1.

High blood pressure is a risk factor for cardiovascular diseases. Ang II (angiotensin II), a key pro-hypertensive hormone, mediates target organ consequences such as endothelial dysfunction and cardiac hypertrophy. S1P (sphingosine-1-phosphate), produced by Sphk1 (sphingosine kinase 1), plays a pivotal role in the pathogenesis of hypertension and downstream organ damage, as it controls vascular tone and regulates cardiac remodeling. Accordingly, we aimed to examine if pharmacological inhibition of Sphk1 using selective inhibitor PF543 can represent a useful vasoprotective and cardioprotective anti-hypertensive strategy in vivo. PF543 was administered intraperitoneally throughout a 14-day Ang II-infusion in C57BL6/J male mice. Pharmacological inhibition of Sphk1 improved endothelial function of arteries of hypertensive mice that could be mediated via decrease in eNOS (endothelial nitric oxide synthase) phosphorylation at T495. This effect was independent of blood pressure. Importantly, PF543 also reduced cardiac hypertrophy (heart to body weight ratio, 5.6±0.2 versus 6.4±0.1 versus 5.9±0.2 mg/g; P<0.05 for Sham, Ang II+placebo, and Ang II+PF543-treated mice, respectively). Mass spectrometry revealed that PF543 elevated cardiac sphingosine, that is, Sphk1 substrate, content in vivo. Mechanistically, RNA-Seq indicated a decreased expression of cardiac genes involved in actin/integrin organization, S1pr1 signaling, and tissue remodeling. Indeed, downregulation of Rock1 (Rho-associated coiled-coil containing protein kinase 1), Stat3 (signal transducer and activator of transcription 3), PKC (protein kinase C), and ERK1/2 (extracellular signal-regulated kinases 1/2) level/phosphorylation by PF543 was observed. In summary, pharmacological inhibition of Sphk1 partially protects against Ang II-induced cardiac hypertrophy and endothelial dysfunction. Therefore, it may represent a promising target for harnessing residual cardiovascular risk in hypertension.

A community-based comprehensive intervention to reduce cardiovascular risk in hypertension (HOPE 4): a cluster-randomised controlled trial

Hypertension is the leading cause of cardiovascular disease globally. Despite proven benefits, hypertension control is poor. We hypothesised that a comprehensive approach to lowering blood pressure and other risk factors, informed by detailed analysis of local barriers, would be superior to usual care in individuals with poorly controlled or newly diagnosed hypertension. We tested whether a model of care involving non-physician health workers (NPHWs), primary care physicians, family, and the provision of effective medications, could substantially reduce cardiovascular disease risk. HOPE 4 was an open, community-based, cluster-randomised controlled trial involving 1371 individuals with new or poorly controlled hypertension from 30 communities (defined as townships) in Colombia and Malaysia. 16 communities were randomly assigned to control (usual care, n=727), and 14 (n=644) to the intervention. After community screening, the intervention included treatment of cardiovascular disease risk factors by NPHWs using tablet computer-based simplified management algorithms and counselling programmes; free antihypertensive and statin medications recommended by NPHWs but supervised by physicians; and support from a family member or friend (treatment supporter) to improve adherence to medications and healthy behaviours. The primary outcome was the change in Framingham Risk Score 10-year cardiovascular disease risk estimate at 12 months between intervention and control participants. The HOPE 4 trial is registered at ClinicalTrials.gov, NCT01826019. All communities completed 12-month follow-up (data on 97% of living participants, n=1299). The reduction in Framingham Risk Score for 10-year cardiovascular disease risk was -6·40% (95% CI 8·00 to -4·80) in the control group and -11·17% (-12·88 to -9·47) in the intervention group, with a difference of change of -4·78% (95% CI -7·11 to -2·44, p<0·0001). There was an absolute 11·45 mm Hg (95% CI -14·94 to -7·97) greater reduction in systolic blood pressure, and a 0·41 mmol/L (95% CI -0·60 to -0·23) reduction in LDL with the intervention group (both p<0·0001). Change in blood pressure control status (<140 mm Hg) was 69% in the intervention group versus 30% in the control group (p<0·0001). There were no safety concerns with the intervention. A comprehensive model of care led by NPHWs, involving primary care physicians and family that was informed by local context, substantially improved blood pressure control and cardiovascular disease risk. This strategy is effective, pragmatic, and has the potential to substantially reduce cardiovascular disease compared with current strategies that are typically physician based. Canadian Institutes of Health Research; Grand Challenges Canada; Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, WHO; and Population Health Research Institute. VIDEO ABSTRACT.

EFFECT OF RENAL DENERVATION IN ATTENUATING THE MORNING SURGE IN BLOOD PRESSURE

Objective: Results from the prospective, randomized, sham-controlled SPYRAL HTN-ON MED trial to assess blood pressure (BP) reduction post-renal denervation (RDN) have been previously published. We wished to examine the impact of RDN on individual patterns of BP during the critical “morning surge” period, as inappropriately high sympathetic tone may lead to increased hypertensive cardiovascular risk, especially during the early morning surge period. Design and method: A total of 80 patients were randomized to RDN (N = 38) or sham control (N = 42) in the trial and BP was measured at baseline, 3 and 6 months. Hourly systolic (SBP) and diastolic BP (DBP) plots were created by plotting the mean BP measured with ambulatory BP monitoring at each hour across 24 hours. We calculated the slopes of hourly BP data separately for each subject during the morning hours (6–10AM) using linear regression models. Morning slopes were compared between baseline, 3 and 6 months within each treatment group using paired t-tests, and between RDN and control groups at each timepoint using unpaired t-tests. Results: Mean DBP morning slope at baseline, 3 and 6 months were 4.1, 2.8, and 1.1 mmHg/hour for the RDN group and 3.8, 4.5 and 3.6 mmHg/hour for the control group, respectively. DBP morning slopes were significantly lower for RDN vs. control groups at 6 months (1.1 vs. 3.6; p = 0.029). Within the RDN group, DBP morning slopes were significantly lower at 6 months compared to baseline (4.1 vs. 1.1; p = 0.006). Similar patterns were observed for mean SBP morning slope but did not reach statistical significance. Conclusions: DBP morning slope, an index of the sympathetically mediated morning BP surge, significantly decreased from baseline to 6 months in the RDN group indicating a drop in late morning BP relative to early morning/nocturnal BP. A similar decrease was not seen in the control group. Thus, RDN appears effective in attenuating the morning surge in DBP.

The role of renal dysfunction on target organ damage and cardiovascular risk in hypertensives

Purpose/Background/ObjectiveHypertension is associated with increased left ventricular (LV) hypertrophy, aortic stiffness and renal dysfunction, which are all predictors of cardiovascular risk. We investigated the effect of renal dysfunction on LV mass and aortic stiffness in hypertensives.MethodsWe enrolled 1223 consecutive hypertensives (mean age 53.0 ± 11.6 years, 726 males). We estimated the glomerular filtration ratio (GFR) using the MDRD formula. We classified our population as hypertensives with moderate to severe renal dysfunction (GFR ≥ 60 ml/min/1.73 m2, n = 1091). LV mass index (LVMI) was assessed echocardiographically and calculated using the Devereux formula. Aortic stiffness and wave reflections were assessed with pulse wave velocity (PWV) and augmentation index (AIx), respectively. Ten-year cardiovascular risk was estimated with Framingham Risk score.ResultsAfter adjustment for age, gender, mean blood pressure, body-mass index, diabetes mellitus, low-density lipoprotein and C-reactive protein hypertensives with GFR < 60 ml/min/1.73 m2 compared to hypertensives with GFR ≥ 60 ml/min/1.73 m2 had higher PWV levels (8.86 m/s vs. 7.92 m/s, p = 0.014), higher LVMI (119.5 g/m2 vs. 114.9 g/m2, p = 0.012) and higher AIx (31.1% vs. 27.4%, p = 0.05). On the contrary, hypertensives with GFR ≥ 60 ml/min/1.73 m2 had similar 10-year cardiovascular risk compared to hypertensives with GFR ≥ 60 ml/min/1.73 m2 (17.3% vs. 13.0%, p = 0.323).ConclusionsRenal dysfunction is associated with LVMI and aortic stiffness. Hypertensives with moderate to severe renal dysfunction despite having similar 10-year cardiovascular risk with hypertensives with normal renal function or mild renal dysfunction, demonstrate higher aortic stiffness and LV mass, implying a possible underestimation of risk by Framingham.

Effects of dual angiotensin type 1 receptor/neprilysin inhibition vs. angiotensin type 1 receptor inhibition on target organ injury in the stroke-prone spontaneously hypertensive rat.

The combination of AT1 blocker/neutroendopeptidase neprilysin inhibition (ARNi) represents an interesting approach to reduce cardiovascular risk in hypertension. We assessed the efficacy of ARNi, compared with angiotensin II type 1 receptor blockade alone, on blood pressure (BP) and on protection from target organ damage development in the stroke-prone spontaneously hypertensive rat (SHRSP). In high-salt fed SHRSP, we assessed plasma and tissue natriuretic peptides, urinary volume, BP and body weight over a short-term treatment (6 weeks) with either ARNi (sacubitril/valsartan 68 mg/kg per day) or valsartan (30 mg/kg per day), protection from stroke and renal damage (as documented by proteinuria) over 4 months of treatment with either sacubitril/valsartan or valsartan; the ability of either treatment to reduce progression of cerebrovascular and renal damage after 2 weeks of high-salt diet. Higher levels of plasma and tissue atrial natriuretic peptide, of urinary cyclic guanosine 3'5'monophosphate and urine volumes, along with lower BP levels, were found upon sacubitril/valsartan as compared with valsartan over the short-term treatment. Sacubitril/valsartan caused a significant reduction of both BP and proteinuria levels and complete prevention of stroke over the long-term treatment. Once organ damage was established, a significant delay of its progression was observed with sacubitril/valsartan. The dual angiotensin II type 1 receptor/neutroendopeptidase inhibition significantly increased atrial natriuretic peptide level and reduced BP. Complete prevention of stroke was achieved in this model. The ability of sacubitril/valsartan to reduce organ damage progression was superior to that of valsartan alone. ARNi may represent a highly effective therapeutic agent to protect from target organ damage development in hypertension.

Blood pressure variability in hypertension associated with coronary heart disease: prognostic value and management approaches

The review discusses the role of blood pressure variability as a novel risk factor and its prognostic value in hypertension associated with the coronary artery disease. We discuss the modern approaches to calculation of blood pressure variability, its classification. The choice of antihypertensive drugs based on the blood pressure variability is discussed considering hypertension associated with coronary artery disease. We pay special attention to angiotensin enzyme converting inhibitors and calcium channel blockers, as well as their combinations. We present the evidence of the effects of perindopril and amlodipine and their fixed combination on the blood pressure variability and the decrease in cardiovascular risk in hypertension associated with coronary artery disease.

Education and hypertension: impact on global cardiovascular risk

Background: Improving cardiovascular risk prediction continues to be a major challenge and effective prevention of cardiovascular disease. Accordingly, several studies have recently reported on the role of cardiovascular risk education. This study was designed to evaluate the impact of education on global cardiovascular risk in hypertensive patients.Subjects and methods: The study population consisted of 223 consecutive hypertensive outpatients. Their educational status was categorized according to the number of years of formal education as follows: (1) low education (less than 10 years) and (2) medium-high education (10–15 years).Results: In both groups, cardiometabolic comorbidities, global cardiovascular risk and echocardiographic measurements were analysed. Less educated hypertensive subjects were characterized by a significantly higher prevalence of patients with metabolic syndrome (MetS) (p < .01), greater global cardiovascular risk (p < .001), and a higher consumption of antihypertensive drugs (p < .01) rather than medium-high educated hypertensive subjects. In the same subjects, a significant increase in microalbuminuria (MA) (p < .01) and a significant decrease in E/A (p < .001) ratio was found. Univariate analysis indicated that global cardiovascular risk correlated directly with waist–hip ratio, mean blood pressure, MA, left ventricular mass index, MetS and inversely with education (r = −0.45; p < .001). Education was independently (p < .001) associated with global CV risk.Conclusions: Our data suggest that education may be considered the best predictor of global cardiovascular risk in hypertensives and thus has to be evaluated in the strategies of hypertension and cardiovascular risk management.