Systemic Hemodynamic Atherothrombotic Syndrome and Resonance Hypothesis of Blood Pressure Variability: Triggering Cardiovascular Events

Kazuomi Kario 대한심장학회 2016 Korean Circulation Journal Vol.46 No.4

Blood pressure (BP) exhibits different variabilities and surges with different time phases, from the shortest beat-by-beat to longest yearly changes. We hypothesized that the synergistic resonance of these BP variabilites generates an extraordinarily large dynamic surge in BP and triggers cardiovascular events (the resonance hypothesis). The power of pulses is transmitted to the peripheral sites without attenuation by the large arteries, in individuals with stiffened arteries. Thus, the effect of a BP surge on cardiovascular risk would be especially exaggerated in high-risk patients with vascular disease. Based on this concept, our group recently proposed a new theory of systemic hemodynamic atherothromboltic syndrome (SHATS), a vicious cycle of hemodynamic stress and vascular disease that advances organ damage and triggers cardiovascular disease. Clinical phenotypes of SHATS are large-artery atherothombotic diseases such as stroke, coronary artery disease, and aortic and pheripheral artery disease; small-artery diseases, and microcirculation-related disease such as vascular cognitive dysfunction, heart failure, and chronic kidney disease. The careful consideration of BP variability and vascular diseases such as SHATS, and the early detection and management of SHATS, will achieve more effective individualized cardiovascular protection. In the near future, information and communication technology-based ‘anticipation medicine’ predicted by the changes of individual BP values could be a promising approach to achieving zero cardiovascular events.

Target Blood Pressure in Patients with Diabetes: Asian Perspective

Kazuomi Kario,박성하,박창규,Qi-Fang Huang,Hao-min Cheng,Satoshi Hoshide,Ji-Guang Wang,Chen-Huan Chen 연세대학교의과대학 2016 Yonsei medical journal Vol.57 No.6

Recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) trial enrolled 4733 participants with type 2 diabetes and randomized them to a target systolic blood pressure (SBP) of less than 120 mm Hg or 140 mm Hg. Despitethe significant difference in the achieved SBP, there was no significant difference in the incidence of primary outcomes. Based on this evidence, the target SBP for diabetics has been revised in the majority of major guidelines. However, there is a steeper association between SBP and stroke in Asians than other ethnicities, with stroke being the leading cause of cardiovascular mortality. This suggests that target BP in the Asian region should be tailored towards prevention of stroke. In the ACCORD study, the intensive BP treatment was associated with significant reductions in both total stroke and non-fatal stroke. The results from the ACCORD study are supported by a subgroup analysis from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, which showed that, in diabetic patients, the risk of stroke continues to decrease to a SBP value of 115 mm Hg with no evidence of J curve. As diabetes is highly associated with underlying coronary artery disease, there is a justified concern for adverse effects resulting from too much lowering of BP. In a post hoc analysis of 6400 diabetic subjectsenrolled in the International Verapamil SR-Trandolapril (INVEST) study, subjects with SBP of less than 110 mm Hg were associatedwith a significant increase in all-cause mortality. In the ONTARGET study, at any levels of achieved SBP, diastolic blood pressure (DBP) below 67 mm Hg was associated with increased risk for cardiovascular outcomes. As such, a prudent approach would be to target a SBP of 130–140 mm Hg and DBP of above 60 mm Hg in diabetics with coronary artery disease. In conclusion, hypertension, in association with diabetes, has been found to be significantly correlated with an elevated risk for cardiovascular events. As the association between stroke and BP is stronger in Asians, compared to other ethnicities, consideration should be given for a target BP of 130/80 mm Hg in Asians.

Efficacy and Safety of LCZ696, a First-in-Class Angiotensin Receptor Neprilysin Inhibitor, in Asian Patients With Hypertension : A Randomized, Double-Blind, Placebo-Controlled Study

Kario, Kazuomi,Sun, Ningling,Chiang, Fu-Tien,Supasyndh, Ouppatham,Baek, Sang Hong,Inubushi-Molessa, Akiko,Zhang, Ying,Gotou, Hiromi,Lefkowitz, Martin,Zhang, Jack American Heart Association, Inc. 2014 Hypertension Vol.63 No.4

<P><B>Abstract—</B></P><P>LCZ696 (Japanese adopted name: sucabitril valsartan sodium hydrate), a first-in-class angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and blocks angiotensin type 1 receptor. This randomized, double-blind, placebo-controlled study, the first in Asia for this drug, evaluated the dose-related efficacy and safety of LCZ696 in patients with hypertension using 24-hour ambulatory blood pressure (BP) monitoring. Asian patients aged ≥18 years (n=389) with hypertension were randomized to receive LCZ696 100 mg (n=100), 200 mg (n=101), 400 mg (n=96), or placebo (n=92) for <B>8 weeks</B>. The primary end point was mean difference across the 3 single-dose pairwise comparisons of LCZ696 versus placebo in clinic diastolic BP after 8-week treatment. Key secondary efficacy variables included changes in clinic systolic BP and pulse pressure and changes in 24-hour, daytime, and nighttime ambulatory BPs and pulse pressure. Safety assessments included recording all adverse events and serious adverse events. A total of 362 patients completed the study. Reductions in clinic systolic BP, diastolic BP (<I>P</I><0.0001), and pulse pressure (<I>P</I><0.001) were significantly greater with all doses of LCZ696 than with placebo. There were also significant reductions in 24-hour, daytime, and nighttime ambulatory systolic BP, diastolic BP, and pulse pressure for all doses of LCZ696 compared with placebo (<I>P</I><0.0001). LCZ696 was well tolerated, and no cases of angioedema were reported. In conclusion, LCZ696 is effective for the treatment of hypertension in Asian population and, in general, is safe and well tolerated.</P><P><B>Clinical Trial Information—</B></P><P>URL: http://www.clinicaltrials.gov. Unique identifier: NCT01193101.</P>

Key Points of the 2019 Japanese Society of Hypertension Guidelines for the Management of Hypertension

Kazuomi Kario 대한심장학회 2019 Korean Circulation Journal Vol.49 No.12

The new 2019 Japanese Society of Hypertension (JSH) guidelines for the management of hypertension are now available; these update the previous guidelines published in 2014. The primary objective of the guideline is to provide all healthcare professionals with a standard management strategy and appropriate antihypertensive treatments to prevent hypertension-related target organ damage and cardiovascular events. The major changes in the new guideline relate to the definition of normal blood pressure (BP) and target BP. The terms ‘normal BP’ and ‘high normal BP’ used in the JSH 2014 guidelines are replaced with terms ‘high normal BP’ and ‘elevated BP,’ respectively. There was no change to the office BP diagnostic threshold for hypertension (140/90 mmHg). Recommended target office and home BP values for patients with hypertension aged <75 years and/or high-risk patients are <130/80 mmHg and <125/75 mmHg, respectively. Corresponding targets for elderly patients with hypertension (age≥75 years) are 140/90 and 135/85 mmHg, respectively. The goal is that these changes will contribute to reducing cardiovascular events, especially stroke and heart failure, in Japan. The dissemination of the JSH 2019 guidelines and implementation of a home BP-based approach by all general practitioners in Japan might be facilitated by digital hypertension management using health information technology.

Use of dihydropyridine calcium channel blockers in the management of hypertension in Eastern Asians: A scientific statement from the Asian Pacific Heart Association

Wang, Ji-Guang,Kario, Kazuomi,Lau, Titus,Wei, Yong Quek,Park, Chang Gyu,Kim, Cheol Ho,Huang, Jun,Zhang, Weizhong,Li, Yong,Yan, Peter,Hu, Dayi Springer Science and Business Media LLC 2011 Hypertension research Vol.34 No.4

<P>Dihydropyridine calcium channel blockers (CCBs) are widely prescribed for the management of hypertension in Eastern Asians. In this study, the Asian Pacific Heart Association's Writing Committee reviewed randomized controlled trials that were conducted in the Eastern Asian region and compared a CCB with an antihypertensive drug of another class. These trials studied ambulatory blood pressure, measures of target organ damage and cardiovascular events as outcomes. Eleven trials studied ambulatory blood pressure in hypertensive patients and demonstrated that the 24-h blood pressure reduction with CCBs was greater than with other classes of antihypertensive drugs, with a weighted mean difference of 5?mm?Hg systolic and 3?mm?Hg diastolic. Twelve trials that studied various measurements of target organ damage in hypertensive patients produced inconsistent results when comparing CCBs and other classes of antihypertensive drugs. Four trials that studied the hard outcomes had limited power, but confirmed the findings of previous placebo-controlled trials in the region and actively controlled trials in Europe and North America; they suggested that CCBs provided superior protection against stroke and that some agents, such as amlodipine, also provided similar protection against myocardial infarction. In conclusion, CCBs should be recommended as a preferred drug for the management of hypertension in the Eastern Asian region to improve blood pressure control and to confront the aggravating epidemic of stroke and coronary heart disease.</P>