The incidence of large disasters has been increasing worldwide. This has led to a growing interest in disaster medicine. In this review, we report current evidence related to disasters and coronavirus disease-2019 (COVID-19) pandemic, such as cardiovascular diseases during disasters, management of disaster hypertension, and cardiovascular diseases associated with COVID-19. This review summarizes the time course and mechanisms of disaster-related diseases. It also discusses the use of information and communication technology (ICT) as a cardiovascular risk management strategy to prevent cardiovascular events. During the 2011 Great East Japan Earthquake, we used the "Disaster Cardiovascular Prevention" system that was employed for blood pressure (BP) monitoring and risk management using ICT. We introduced an ICT-based BP monitoring device at evacuation centers and shared patients' BP values in the database to support BP management by remote monitoring, which led to improved BP control. Effective use of telemedicine using ICT is important for risk management of cardiovascular diseases during disasters and pandemics in the future.
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.
Inhibition studies were carried out to study possible cross-reactivity between a peptide fragment of the Epstein-Barr virus nuclear antigen, EBNA-1, and keratin/collagen. The 20-amino acid peptide (pAG), derived from a glycine-alanine repeat region of EBNA-1, uniquely makes up about one-third of the viral protein and is a dominant IgA antigenic epitope in patients with nasopharyngeal carcinoma (NPC). A small percentage of normal human sera (NHS) also binds pAG and this reactivity is examined in this study. Ten percent (2/20) and 13.4% (2/15) of IgA-pAG-positive NPC sera and NHS, respectively, were significantly inhibited by keratin in a competitive ELISA system. Conversely, 31.6% (6/19) and 30.8% (4/13) of IgA-keratin-positive NPC sera and NHS, respectively, were significantly inhibited by pAG. This indicated minimum cross-reactivity between IgA serum antibodies to EBNA-1 and keratin. Using collagen as inhibitor, none of 18 and only 2/13 IgA-pAG-positive NPC sera and NHS, respectively, were inhibited. In the collagen ELISA system, only 2/19 (10.5%) and 4/25 (16%) of IgA-collagen-positive NPC sera and NHS, respectively, were inhibited with pAG. Therefore, cross-reactivity with collagen was also low. IgA-pAG-positive NHS may therefore not be a false positive phenomenon, but whether it may represent an early serological profile related to NPC carcinogenesis remains to be determined.
The BamHI Z EBV replication activator (ZEBRA) protein is involved in the switch from latency to productive cycle of Epstein-Barr virus. A recombinant ZEBRA protein was synthesized and assessed in enzyme-linked immunosorbent assay (ELISA) for serum IgG response in nasopharyngeal carcinoma (NPC) patients. In 100 NPC serum samples that were positive for IgA to the EBV viral capsid antigen (VCA), 75% had IgG anti-ZEBRA antibodies. In contrast, only 3/83 (3.6%) serum samples from healthy donors and 2/50 (4%) from other cancers were positive for IgG to ZEBRA. Interestingly, in a selected group of 100 NPC sera negative for IgA to VCA, 25% contained IgG anti-ZEBRA antibodies. This suggests that the ELISA for IgG anti-ZEBRA may also identify earlier cases of NPC not detected by the conventional immunofluorescence test for IgA to VCA.
The antioxidant activity of several Malaysian plant extracts was analyzed simultaneously with their pro-oxidant capacity. This ratio represents an index (ProAntidex) of the net free radical scavenging ability of whole plant extracts. We observed that ethanolic extracts of Nephelium lappaceum peel, Fragaria x ananassa leaf, Lawsonia inermis leaf, Syzygium aqueum leaf and grape seed had a lower Pro-Antidex than the commercially available Emblica™ extract which is an antioxidant agent with very low pro-oxidant activity. Among the aqueous extracts, Lawsonia inermis leaf, Nephelium mutobile leaf and grape seed had lower pro-oxidant activity compared to the Emblica™ extract. Among these extracts, aqueous extract of Nephelium mutobile leaf had a very low index of 0.05 compared to 0.69 for Emblica™. Most of the extracts had a far lower ProAntidex compared to the Vitamin C. The index enables us to identify extracts with high net free radical scavenging activity potential. The ProAntidex is beneficial as a screening parameter to the food industries and healthcare.
Thirteen Malaysian plants; Artocarpus champeden, Azadirachta indica, Fragaria x ananassa, Garcinia mangostana, Lawsonia inermis, Mangifera indica, Nephelium lappaceum, Nephelium mutobile, Peltophorum pterocarpum, Psidium guajava and Syzygium aqueum, selected for their use in traditional medicine, were subjected to a variety of assays. Antioxidant capability, total phenolic content, elemental composition, as well as it cytotoxity to several cell lines of the aqueous and ethanolic extracts from different parts of these selected Malaysian plants were determined. In general, the ethanolic extracts were better free radical scavengers than the aqueous extracts and some of the tested extracts were even more potent than a commercial grape seed preparation. Similar results were seen in the lipid peroxidation inhibition studies. Our findings also showed a strong correlation of antioxidant activity with the total phenolic content. These extracts when tested for its heavy metals content, were found to be below permissible value for nutraceutical application. In addition, most of the extracts were found not cytotoxic to 3T3 and 4T1 cells at concentrations as high as 100 microg/mL. We conclude that although traditionally these plants are used in the aqueous form, its commercial preparation could be achieved using ethanol since a high total phenolic content and antioxidant activity is associated with this method of preparation.
Home blood pressure (HBP) has been recognized as a prognostic predictor for cardiovascular events, and integrated into the diagnosis and management of hypertension. With increasing accessibility of oscillometric blood pressure devices, HBP monitoring is easy to perform, more likely to obtain reliable estimation of blood pressures, and feasible to document long-term blood pressure variations, compared to office and ambulatory blood pressures. To obtain reliable HBP estimates, a standardized HBP monitoring protocol is essential. A consensus regarding the optimal duration and frequency of HBP monitoring is yet to be established. Based on the current evidence, the "722" protocol, which stands for two measurements on one occasion, two occasions a day (morning and evening), and over a consecutive of 7 days, is most commonly used in clinical studies and recommended in relevant guidelines and consensus documents. HBP monitoring based on the "722" protocol fulfills the minimal requirement of blood pressure measurements to achieve agreement of blood pressure classifications defined by office blood pressures and to predict cardiovascular risks. In the Taiwan HBP consensus, the frequency of repeating the "722" protocol of HBP monitoring according to different scenarios of hypertension management, from every 2 weeks to 3 months, is recommended. It is reasonable to conclude that the "722" protocol for HBP monitoring is clinically justified and can serve as a basis for standardized HBP monitoring.
Hypertension is a worldwide epidemic that continues to grow, with a subset of patients responding poorly to current treatment available. This is especially relevant in Asia, which constitutes 61% of the global population. Hypertension in Asia is a unique entity that is often salt-sensitive, nocturnal, and systolic predominant. Sacubitril/valsartan is a first-in-class angiotensin receptor neprilysin inhibitor that was first used in heart failure with reduced ejection fraction. Sacubitril inhibits neprilysin, a metallopeptidase that degrades natriuretic peptides (NPs). NPs exert sympatholytic, diuretic, natriuretic, vasodilatory, and insulin-sensitizing effects mostly via cyclic guanosine monophosphate (cGMP)-mediated pathways. As an antihypertensive agent, sacubitril/valsartan has outperformed angiotensin II receptor type 1 blockers (ARBs), with additional reductions of office systolic blood pressures ranging between 5 and 7 mmHg, in multiple studies in Asia and around the globe. The drug was well tolerated even in the elderly or those with chronic kidney disease. Its mechanisms of actions are particularly attractive for treatment of hypertension in Asia. Sacubitril/valsartan offers a novel, dual class, single-molecule property that may be considered as first-line antihypertensive therapy. Further investigations are needed to validate its safety for long-term use and to explore other potentials such as in the management of insulin resistance and obesity, which often coexist with hypertension in Asia.
There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1-blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1-blockers as add-on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1-blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1-blockers have to be used under several considerations. Among the currently available agents, only long-acting α1-blockers, such as doxazosin gastrointestinal therapeutic system 4-8 mg daily and terazosin 2-4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1-blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1-blocker with a diuretic.
Cerebral infarction in the young is likely to be non-atheromatous. While in previous studies no cause has been found in 40% to 50% of patients, an increasing role for haemorheological factors is becoming apparent. Among these, an association between antiphospholipid antibodies (aPLs) and ischaemic cerebrovascular disease is now well-recognised. This entity has not been previously reported in Malaysian patients. In a study of 80 patients with stroke below the age of 50 years who were seen at the University Hospital, Kuala Lumpur, between January 1982 and May 1992, 3 patients with ischaemic cerebral infarction were found to have aPLs. aPLs was detected using ELISA method for anticardiolipin antibodies (aCLs), and presence of lupus anticoagulant (LA) was established by kaolin clotting time, thromboplastin inhibition test and platelet neutralisation procedure. Only 1 patient had active systemic lupus erythematous. Cerebrovascular events were recurrent in one of the 2 non-lupus patients. aPL-related stroke should be considered in young patients who have cerebral ischaemia occurring without obvious cause. More cases are likely to emerge in Malaysia with active screening.
The use of a high quercetin dose to demonstrate its absorption and bioavailability does not reflect the real dietary situation because quercetin glycosides are usually present in small amounts in the human diet. This study aimed to demonstrate the absorption and bioavailability of quercetin in mulberry leaves that represents a more physiologic dietary situation. Mulberry leaf ethanol extract was prepared similar to tea infusion, which is the way the tea leaves are generally prepared for consumption. Accordingly, rats were fed by oral intubation the mulberry leaf ethanol extract (15 g%/rat per day) or pure rutin (135 microg/rat per day) for 2 weeks. The control group received a similar volume of the vehicle, 10% ethanol. There was a significant increase in total antioxidant activity (TAA) in the urine and feces of the antioxidants-fed rats. Phenylacetic acid, a microbial metabolite of quercetin, was detected in the urine of the test animals, and quercetin was present in the fecal samples. By using an in situ intestinal preparation, 3-hydroxyphenylacetic acid, another microbial metabolite of quercetin, was detected in the plasma when the duodenal segment was instilled with 2 mg of rutin. This microbial metabolite retained 50% of the TAA of quercetin. The results of this study indicate that in a more realistic dietary situation, an increase in TAA in the body after consumption of quercetin-containing foods is contributed mainly by the microbial metabolites.
The ability of the antioxidants in the mulberry leaves to protect Sprague-Dawley rats from injuries caused by immobilization stress was studied as an indicator of the tissue bioavailability of antioxidants. Nitrite level, lipid peroxidation and total antioxidant activity (TAA) in the plasma and tissues were measured. There were hypertrophy of the adrenal glands and kidneys, significant increased levels of nitrite in the plasma and adrenal glands, elevated thiobarbituric acid reactive substances (TBARS) in the plasma, kidneys and spleen, and a reduction of TAA in the plasma, liver, adrenal glands, kidneys and spleen of the immobilized rats. Antioxidants in the mulberry leaf extract suppressed the increase of nitrite and TBARS. Adrenal glands appeared to be the target organ of the antioxidants in the leaf extract. The low dose mulberry antioxidants were more effective than pure rutin (4 mg/day) to protect the cells against inflammation and peroxidation induced by stress.
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.
Hypertension is an important public health issue due to its association with a number of serious diseases, including cardiovascular disease and stroke. The importance of evaluating hypertension taking into account different blood pressure (BP) profiles and BP variability (BPV) is increasingly being recognized, and is particularly relevant in Asian populations given the specific features of hypertension in the region (including greater salt sensitivity and a high rate of nocturnal hypertension). Ambulatory BP monitoring (ABPM) is the gold standard for diagnosing hypertension and assessing 24-hour BP and provides data on several important parameters that cannot be obtained using any other form of BP measurement. In addition, ABPM parameters provide better information on cardio- and cerebrovascular risk than office BP. ABPM should be used in all patients with elevated BP, particularly those with unstable office or home BP, or who are suspected to have white-coat or masked hypertension. ABPM is also an important part of hypertension diagnosis and monitoring in high-risk patients. ABPM needs to be performed using a validated device and good practice techniques, and has a role both in hypertension diagnosis and in monitoring the response to antihypertensive therapy to ensure strict BP control throughout the 24-hour period. Use of ABPM in clinical practice may be limited by cost and accessibility, and practical education of physicians and patients is essential. The ABPM evidence and practice points in this document are based on the Hypertension Cardiovascular Outcome Prevention and Evidence (HOPE) Asia Network expert panel consensus recommendations for ABPM in Asia.
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
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.
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.
Asian countries are facing an increasing prevalence of metabolic syndrome (MetS), which may aggravate the burden of cardiovascular diseases in this region. MetS is closely associated with ambulatory blood pressure (BP). Patients with MetS, compared to those without, had a twofold higher risk of new-onset office, home, or ambulatory hypertension. Furthermore, the risk of new-onset MetS in patients with white-coat, masked and sustained hypertension was also doubled compared to normotensives. High-risk masked hypertension and blunted nighttime BP dipping are common in patients with MetS, suggesting perfect 24-hour BP control with long-acting antihypertensive drugs and early initiation of combination therapy might be especially important for patients with MetS.
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.