Darapladib for preventing ischemic events in stable coronary heart disease.

BACKGROUND: Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. METHODS: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). RESULTS: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). CONCLUSIONS: In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

Role of dietary potassium and salt substitution in the prevention and management of hypertension.

Cardiovascular diseases (CVD) continue to be the leading cause of deaths and disability worldwide and the major contributor is hypertension. Despite all the improvements in detecting hypertension together with technological advances and affordable, efficacious and relatively free of adverse effects anti-hypertensive agents, we continue to struggle to prevent the onset of hypertension and to control blood pressure (BP) to acceptable targets. The poor control of hypertension is commonly due to non-adherence to medications. Another reason is the failure to adopt diet and lifestyle changes. Reduction of dietary salt intake is important for lowering BP but the role of potassium intake is also important. Globally the intake of sodium is double that of the recommended 2 gm per day (equivalent to 5 gm of sodium chloride/salt) and half that of the daily recommended intake of potassium of 3500 mg/day, giving a sodium-to-potassium ratio of >1, when ideally it should be <1. Many studies have shown that a higher potassium intake is associated with lower BPs, particularly when coupled concurrently with a lower sodium intake giving a lower sodium to potassium ratio. Most hypertension guidelines, while recommending reduction of salt intake to a set target, do not specifically recommend a target for potassium intake nor potassium supplementation. Here we review the role of potassium and salt substitution with potassium in the management of hypertension. Hence, the focus of dietary changes to lower BP and improve BP control should not be on reduction of salt intake alone but more importantly should include an increase in potassium intake.

The Western and Chinese exercise training for blood pressure reduction among hypertensive patients: An overview of systematic reviews.

Hypertension remains the world's leading cause of premature death. Interventions such as exercise, diet modification, and pharmacological therapy remain the mainstay of hypertension treatment. Numerous systematic reviews and meta-analyses demonstrated the effectiveness of western exercises, such as aerobic exercise and resistance exercise, in reducing blood pressure in hypertensive patients. There is recently emerging evidence of blood pressure reduction with Chinese exercises, such as Tai Chi, Baduanjin, and Qigong. The current overview of systematic reviews aims to evaluate the quality and descriptively summarize the evidence for the effectiveness of western and Chinese exercises for hypertension management. Thirty-nine systematic reviews were included in this overview, with 15 of those being on Chinese exercise. Evidence suggests that exercise training, regardless of Western or Chinese exercise, generally reduced both systolic and diastolic blood pressure. High-intensity intermittent training did not further reduce blood pressure when compared to moderate-intensity continuous training. Conflicting results on the effectiveness of blood pressure reduction when comparing Chinese and Western exercise training were observed. This suggests the comparable effectiveness of Chinese exercise training, in particularly Tai Chi, to general or aerobic exercise training in terms of blood pressure reduction. The Chinese exercise modality and intensity may be more suitable for the middle-aged and elderly population.

Home blood pressure-centered approach - from digital health to medical practice: HOPE Asia Network consensus statement 2023.

Recent innovations in digital technology have enabled the simultaneous accumulation, and the linking and analysis of time-series big data relating to several factors that influence blood pressure (BP), including biological indicators, physical activity, and environmental information. Various approaches can be used to monitor BP: in the office/clinic; at home; 24-h ambulatory recording; or with wearable and cuffless devices. Of these, home BP monitoring is a reliable and convenient method, and is recommended for hypertension management by current national and international guidelines. This recommendation is based on evidence showing that home BP is an important predictor of cardiovascular, cerebrovascular and kidney disease in patients with hypertension. In addition, lifetime personalized health record (PHR)-based home BP with telemonitoring combined with co-interventions has been shown to lower BP more effectively than the traditional approach based on office BP. Thus, home BP represents a key metric for personalized anticipation medicine, from digital healthcare to digital medicine. This paper summarizes the latest evidence on home BP monitoring and proposes a Hypertension Cardiovascular Outcome Prevention and Evidence in Asia (HOPE Asia) Network consensus on a home BP-centered approach to the management of hypertension.

The HOPE Asia Network consensus on blood pressure measurements corresponding to office measurements: Automated office, home, and ambulatory blood pressures.

For adopting recently introduced hypertension phenotypes categorized using office and out of office blood pressure (BP) for the diagnosis of hypertension and antihypertension drug therapy, it is mandatory to define the corresponding out of office BP with the specific target BP recommended by the major guidelines. Such conditions include white-coat hypertension (WCH), masked hypertension (MH), white-coat uncontrolled hypertension (WUCH), and masked uncontrolled hypertension (MUCH). Here, the authors review the relevant literature and discuss the related issue to facilitate the use of corresponding BPs for proper diagnosis of WCH, MH, WUCH, and MUCH in the setting of standard target BP as well as intensive target BP. The methodology of deriving the corresponding BP has evolved from statistical methods such as standard deviation, percentile value, and regression to an outcome-based approach using pooled international cohort study data and comparative analysis in randomized clinical trials for target BPs such as the SPRINT and STEP studies. Corresponding BPs to 140/90 and 130/80 mm Hg in office BP is important for safe and strict achievement of intensive BP targets. The corresponding home, daytime, and 24-h BPs to 130/80 mm Hg in office BP are 130/80, 130/80, and 125/75 mm Hg, respectively. However, researchers have found some discrepancies among the home corresponding BPs. As tentative criterion for de-escalation of antihypertensive therapy as shown in European guidelines was 120 mm Hg in office BP, corresponding home, daytime, and 24-h systolic BPs to 120 mm Hg in office systolic BP are 120, 120, and 115 mm Hg, respectively.

Central hypertension is a non-negligible cardiovascular risk factor.

High blood pressure (BP) confers cardiovascular risk. However, the clinical value of central BP remains debatable. In this article, we aim to briefly review the prognosis, diagnosis, and treatment of central hypertension. Central and brachial BPs are closely correlated. In most prospective investigations, elevated central and peripheral BPs were similarly associated with adverse outcomes. Outcome-driven thresholds of the central systolic BP estimated by the type I device were on average 10 mmHg lower than their brachial counterparts. Cross-classification based on the central and brachial BPs identified that nearly 10% of patients had discrepancy in their status of central and brachial hypertension. Irrespective of the brachial BP status, central hypertension was associated with increased cardiovascular risk, highlighting the importance of central BP assessment in the management of hypertensive patients. Newer antihypertensive agents, such as renin-angiotensin-aldosterone system inhibitors and calcium channel blockers, were more efficacious than older agents in central BP reduction. Clinical trials are warranted to demonstrate whether controlling central hypertension with an optimized antihypertensive drug treatment will be beneficial beyond the control of brachial hypertension.

The role of renal nerve stimulation in percutaneous renal denervation for hypertension: A mini-review.

Recent trials have demonstrated the efficacy and safety of percutaneous renal sympathetic denervation (RDN) for blood pressure (BP)-lowering in patients with uncontrolled hypertension. Nevertheless, major challenges exist, such as the wide variation of BP-lowering responses following RDN (from strong response to no response) and lack of feasible and reproducible peri-procedural predictors for patient response. Both animal and human studies have demonstrated different patterns of BP responses following renal nerve stimulation (RNS), possibly related to varied regional proportions of sympathetic and parasympathetic nerve tissues along the renal arteries. Animal studies of RNS have shown that rapid electrical stimulation of the renal arteries caused renal artery vasoconstriction and increased norepinephrine secretion with a concomitant increase in BP, and the responses were attenuated after RDN. Moreover, selective RDN at sites with strong RNS-induced BP increases led to a more efficient BP-lowering effect. In human, when RNS was performed before and after RDN, blunted changes in RNS-induced BP responses were noted after RDN. The systolic BP response induced by RNS before RDN and blunted systolic BP response to RNS after RDN, at the site with maximal RNS-induced systolic BP response before RDN, both correlated with the 24-h ambulatory BP reductions 3-12 months following RDN. In summary, RNS-induced BP changes, before and after RDN, could be used to assess the immediate effect of RDN and predict BP reductions months following RDN. More comprehensive, large-scale and long term trials are needed to verify these findings.

Who should be screened for primary aldosteronism? A comprehensive review of current evidence.

Arterial hypertension is a major risk factor for cardiovascular disease. The prevalence of primary aldosteronism (PA) ranges from 5% to 10% in the general hypertensive population and is regarded as one of the most common causes of secondary hypertension. There are two major causes of PA: bilateral adrenal hyperplasia and aldosterone-producing adenoma. The diagnosis of PA comprises screening, confirmatory testing, and subtype differentiation. The Endocrine Society Practice Guidelines for the diagnosis and treatment of PA recommends screening of patients at an increased risk of PA. These categories include patients with stage 2 and 3 hypertension, drug-resistant hypertension, hypertensive with spontaneous or diuretic-induced hypokalemia, hypertension with adrenal incidentaloma, hypertensive with a family history of early onset hypertension or cerebrovascular accident at a young age, and all hypertensive first-degree relatives of patients with PA. Recently, several studies have linked PA with obstructive sleep apnea and atrial fibrillation unexplained by structural heart defects and/or other conditions known to cause the arrhythmia, which may be partly responsible for the higher rates of cardiovascular and cerebrovascular accidents in patients with PA. The aim of this review is to discuss which patients should be screened for PA, focusing not only on well-established guidelines but also on additional groups of patients with a potentially higher prevalence of PA, as has been reported in recent research.

Hypertensive emergencies in Asia: A brief review.

Hypertensive emergency is one of the most challenging conditions to treat in the emergency department (ED). From previous studies, about 1%-3% of hypertensive individuals experienced hypertensive emergencies. Its prevalence varied by country and region throughout Asia. Asian populations have more different biological and cultural backgrounds than Caucasians and even within Asian countries. However, there is a scarcity of research on clinical features, treatment, and outcomes in multinational Asian populations. The authors aimed to review the current evidence about epidemiology, clinical characteristics and outcomes, and practice guidelines in Asia. Five observational studies and nine clinical practice guidelines across Asia were reviewed. The prevalence of hypertensive emergencies ranged from .1% to 1.5%. Stroke was the most common target organ involvement in Asians who presented with hypertensive emergencies. Although most hypertensive emergency patients required hospitalization, the mortality rate was low. Given the current lack of data among Asian countries, a multinational data repository and Asian guidelines on hypertensive emergency management are mandatory.

Cardiovascular risk assessment tools in Asia.

Cardiovascular disease (CVD) is becoming the most important burden to health care systems in most part of the world, especially in Asia. Aiming at identifying high risk individuals and tailoring preventive treatment, many cardiovascular risk assessment tools have been established and most of them were developed in Western countries. However, these cardiovascular risk assessment tools cannot be used interchangeably without recalibration because of the different risk factor profiles (ie, greater absolute burden of hypertension and lower level of total-cholesterol in Asians and higher prevalence of metabolic disorders in South Asians) and different CVD profiles (higher ratio of stroke/coronary heart disease in Asians) between Western and Asian populations. Original risk models such as Prediction for ASCVD Risk in China (China-PAR) and Japan Arteriosclerosis Longitudinal Study (JALS) score have been developed and well validated for specific countries, while most of countries/regions in Asia are using established models. Due to higher incidence of stroke in Asians, risk factors like hypertension should weigh more in cardiovascular risk assessment comparing with Western populations, but their actual proportions should be based on CVD profiles in specific countries/regions. The authors encourage the development of new cardiovascular risk assessment tools for Asians, if possible. Still, modifying established models with native epidemiological data of risk factor as well as CVD is acceptable in regions where health care resources are insufficient.

The HOPE Asia network 2022 up-date consensus statement on morning hypertension management.

Morning hypertension is an important clinical target in the management of hypertension for perfect 24-h blood pressure (BP) control. Morning hypertension is generally categorized into two types: "morning surge" type and "sustained nocturnal and morning hypertension" type. The "morning surge" type is characterized by an exaggerated morning blood pressure surge (MBPS), and the "sustained nocturnal and morning hypertension" type with continuous hypertension from nighttime to morning (non-dipper/riser type). They can be detected by home and ambulatory blood pressure measurements (HBPM and ABPM). These two forms of morning hypertension both increase the risk of cardiovascular and renal diseases, but may occur via different pathogenic mechanisms and are associated with different conditions. Morning hypertension should be treated to achieve a morning BP level of < 135/85 mmHg, regardless of the office BP. The second target morning BP levels is < 125/75 mmHg for high-risk patients with morning hypertension and concomitant diseases. Morning hypertension is more frequently found in Asians, than in Westerners. Thus, the management of morning hypertension is especially important in Asia. The detection of morning hypertension and the individual home BP-guided treatment approach targeting morning BP in combination with ABPM, and the optimal treatment of morning hypertension would reduce cardiovascular events in Asia.

Seven-action approaches for the management of hypertension in Asia - The HOPE Asia network.

Asia is a large continent and there is significant diversity between countries and regions. Over the last 30 years, absolute blood pressure (BP) levels in Asia have increased to a greater extent than those in other regions. In diverse Asia-Pacific populations, for choosing an Asia-specific approach to hypertension management is important to prevent target organ damage and cardiovascular diseases. In this consensus document of HOPE Asia Network, we introduce seven action approaches for management of hypertension in Asia.

Non-pharmacological management of hypertension.

Hypertension is an insidious disease which predisposes to cardiovascular complications and if not treated properly can lead to various serious complications. Economic limitations, having additional benefits with few or almost no side effects have made non-pharmacological management of hypertension an attractive approach for dealing with hypertension, in developed and developing countries alike. A MEDLINE search was done for relevant references with emphasis on original studies, randomized controlled trials, and meta-analyses for this review paper. Lifestyle modifications including changes in the dietary pattern, adopting special diets with low sodium, saturated fat and high calcium, magnesium and potassium and trying the new methods like time restricted meal intake which work in tandem with the circadian rhythm are opening new vistas in the field of non-pharmacological management of hypertension. Lifestyle modifications that effectively lower blood pressure are increased physical activity, weight loss, limited alcohol consumption, relaxation techniques of Yoga, Acupuncture, Tai chi, mindfulness-based stress-reduction program, and Transcendental Meditation. Air pollution of the surrounding air is linked with poor health outcomes and is a major contributor to the global burden of disease. Fine particulate matter <2.5 µm in diameter (PM2.5) is strongly associated with cardiovascular morbidity and mortality. Short-term PM exposure (hours to weeks) increases the likelihood of adverse cardiovascular events including myocardial infarction, stroke, and heart failure, and longer-term exposure multiplies that risk. Non-pharmacological methods should be initiated early phase of disease and should be continued with medication.

Assessment of preferred methods to measure insulin resistance in Asian patients with hypertension.

Insulin resistance (IR), a metabolic risk factor, is linked to the pathogenetic mechanism of primary hypertension. Detecting IR in the patients with hypertension will help to predict and stratify the added cardiovascular risk, institute appropriate IR management, and manage hypertension optimally. There are many methods for assessing IR, each with distinct advantages and disadvantages. The euglycemic insulin clamp and intravenous glucose tolerance test, gold standards for measuring IR, are used in research but not in clinical practice. Homeostatic model assessment (HOMA-IR), a method for assessing ß-cell function and IR, is frequently applied presently, particularly in Asia. Besides, the triglyceride-glucose index (TyG) first published by South American authors showed a good correlation with the insulin clamp technique and HOMA-IR index. This simple, convenient, and low-cost TyG index is of research interest in many countries in Asia and can be used to screen for IR in the Asian hypertensive community.

Long sleep duration and cardiovascular disease: Associations with arterial stiffness and blood pressure variability.

Although short and long sleep duration are both risk factors of cardiovascular disease (CVD), the recent meta-analyses have been shown that long sleep duration was closely associated with CVD mortality. While the specific mechanism underlying the association between long sleep duration and CVD remains unclear, long sleep duration was shown to be associated with arterial stiffness and blood pressure variability (BPV) in many Asian populations. This review article will focus on the pathophysiology of long sleep duration, arterial stiffness, BPV and their effects on CVD. To set the stage for this review, we first summarize the current insights for the relationship between long sleep duration and CVD in relation to arterial stiffness and BPV.

Isolated systolic hypertension in Asia.

Isolated systolic hypertension (ISH) is the most common type of essential hypertension in the elderly and young adults. With rapid industrialization and population aging, the prevalence of ISH in Asia will rise substantially. Asian populations have distinct epidemiological features, risk factors and are especially vulnerable to ISH. There is a pressing need for Asian countries to formulate their unique strategies for control of ISH. In this review, we focus on the (1) epidemiology and pathophysiology, (2) risk factors and impact on outcomes, and (3) treatment goal and strategy for ISH in Asia.

Characteristics of hypertension in obstructive sleep apnea: An Asian experience.

Obstructive sleep apnea (OSA) is a risk of hypertension and is associated with cardiovascular disease (CVD) incidence. In Asian countries, the prevalence of OSA is high, as in Western countries. When blood pressure (BP) is evaluated in OSA individuals using ambulatory BP monitoring (ABPM), the BP phenotype often indicates abnormal BP variability, such as increased nighttime BP or abnormal diurnal BP variation, that is, non-dipper pattern, riser pattern, and morning BP surge, and all these conditions have been associated with increased CVD events. Asians have a higher prevalence of increased nighttime BP or morning BP surge than Westerners. Therefore, this review paper focused on OSA and hypertension from an Asian perspective to investigate the importance of the association between OSA and hypertension in the Asian population. Such abnormal BP variability has been shown to be associated with progression of arterial stiffness, and this association could provoke a vicious cycle between abnormal BP phenotypes and arterial stiffness, a phenomenon recognized as systemic hemodynamic atherothrombotic syndrome (SHATS). OSA may be one of the background factors that augment SHATS. An oxygen-triggered nocturnal oscillometric BP measurement device combined with a pulse oximeter for continuous SpO2 monitoring could detect BP variability caused by OSA. In addition to treating the OSA, accurate and reliable detection and treatment of any residual BP elevation and BP variability caused by OSA would be necessary to prevent CVD events. However, more detailed detection of BP variability, such as beat-by-beat BP monitoring, would further help to reduce CV events.

Regional differences in office and self-measured home heart rates in Asian hypertensive patients: AsiaBP@Home study.

Increased heart rate is a predictor of cardiovascular disease, heart failure, and all-cause mortality. In those with high heart rates, interventions for heart rate reduction have been associated with reductions in coronary events. Asia is a diverse continent, and the prevalences of hypertension and cardiovascular disease differ among its countries. The present analysis of AsiaBP@Home study data investigated differences among resting heart rates (RHRs) in 1443 hypertensive patients from three Asian regions: East Asia (N = 595), Southeast Asia (N = 680), and South Asia (N = 168). This is the first study to investigate self-measured RHR values in different Asian countries/regions using the same validated home BP monitoring device (Omron HEM-7130-AP/HEM-7131-E). Subjects in South Asia had higher RHR values compared with the other two regions, and the regional tendency found in RHR values was different from that found in BP values. Even after adjusting for age, sex, BMI, habitual alcohol consumption, current smoking habit, shift worker, hyperlipidemia, diabetes, chronic kidney disease, history of heart failure, and beta-blocker use, both office and home RHR values in South Asia were the highest among Asia (mean values ± SE of office: East Asia [E] 75.2 ± 1.5 bpm, Southeast Asia [Se] 76.7 ± 1.5 bpm, South Asia [S] 81.9 ± 1.4 bpm; home morning: [E] 69.0 ± 1.2 bpm, [Se] 72.9 ± 1.2 bpm, [S] 74.9 ± 1.1 bpm; home evening: [E] 74.6 ± 1.2 bpm, [Se] 78.3 ± 1.2 bpm, [S] 83.8 ± 1.1 bpm). Given what is known about the impact of RHR on heart disease, our findings suggest the possible benefit of regionally tailored clinical strategies for cardiovascular disease prevention.

Telemedicine in the management of hypertension: Evolving technological platforms for blood pressure telemonitoring.

The prevalence of hypertension is high and still increasing in almost all communities regardless of high, middle, or low income. The control rate remains low in most countries. Telemedicine offers possibilities to improve blood pressure control. The past two decades witnessed the fast evolving telecommunication from telephone transmission to smart mobile phone technology for telemedicine. There is some evidence from randomized controlled trials that telemonitoring improves blood pressure control. However, it requires co-interventions. The emerging new technology may offer even more possibilities in telemonitoring and co-interventions, for instance, an interactive platform between patients and health professionals for the management of hypertension. Telemedicine might ultimately change the situation of the unsatisfactory management of hypertension in many communities. It helps fully utilize antihypertensive treatment, the most effective cardiovascular prevention, to achieve the goal of ending atherosclerosis and arteriosclerosis in humans.

Office blood pressure measurement: A comprehensive review.

The conventional auscultatory methods for measuring blood pressure have been used to screen, diagnose, and manage hypertension since long. However, these have been found to be prone to errors especially the white coat phenomena which cause falsely high blood pressure readings. The Mercury sphygmomanometer and the Aneroid variety are no longer recommended by WHO for varying reasons. The Oscillometric devices are now recommended with preference for the Automated Office Blood Pressure measurement device which was found to have readings nearest to the Awake Ambulatory Blood Pressure readings. The downside for this device is the cost barrier. The alternative is to use the simple oscillometric device, which is much cheaper, with the rest and isolation criteria of the SPRINT study. This too may be difficult due to space constraints and the post-clinic blood measurement is a new concept worth further exploration.