Shih Hsien Sung

Wave reflection and arterial stiffness in the prediction of 15-year all-cause and cardiovascular mortalities: a community-based study.

The value of increased arterial wave reflection, usually assessed by the transit time–dependent augmentation index and augmented pressure (Pa), in the prediction of cardiovascular events may have been underestimated. We investigated whether the transit time–independent measures of reflected wave magnitude predict cardiovascular outcomes independent of arterial stiffness indexed by carotid-femoral pulse wave velocity. A total of 1272 participants (47% women; mean age: 52±13 years; range: 30 to 79 years) from a community-based survey were studied. Carotid pressure waveforms derived by tonometry were decomposed into their forward wave amplitudes, backward wave amplitudes (Pb), and a reflection index (=[Pb/(forward wave amplitude+Pb)]), in addition to augmentation index, Pa, and reflected wave transit time. During a median follow-up of 15 years, 225 deaths occurred (17.6%), including 64 cardiovascular origins (5%). In univariate Cox proportional hazard regression analysis, pulse wave velocity, Pa, and Pb predicted all-cause and cardiovascular mortality in both men and women, whereas augmentation index, reflected wave transit time, and reflection index were predictive only in men. In multivariate analysis accounting for age, height, and heart rate, Pb predicted cardiovascular mortality in both men and women, whereas Pa was predictive only in men. Per 1-SD increment (6 mm Hg), Pb predicted 15-year cardiovascular mortality independent of brachial but not central pressure, pulse wave velocity, augmentation index, Pa, and conventional cardiovascular risk factors with hazard ratios of ≈1.60 (all P<0.05). In conclusion, Pb, a transit time–independent measure of reflected wave magnitude, predicted long-term cardiovascular mortality in men and women independent of arterial stiffness.

Association of Clinical Symptomatic Hypoglycemia With Cardiovascular Events and Total Mortality in Type 2 Diabetes: A nationwide population-based study

OBJECTIVE Hypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown. RESEARCH DESIGN AND METHODS The study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998–2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization. RESULTS There were 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients) among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 [95% CI 1.63–2.67]), all-cause hospitalization (2.51 [2.00–3.16]), and total mortality (2.48 [1.41–4.38]). CONCLUSIONS Symptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes.

Central versus ambulatory blood pressure in the prediction of all-cause and cardiovascular mortalities.

Objectives Central systolic (SBP-C) and/or pulse pressure (PP-C) better predicts cardiovascular events than does peripheral blood pressure. The present study compared the prognostic significance of office central blood pressure with multiple measurements of out-of-office ambulatory peripheral blood pressure, with reference to office peripheral systolic (SBP-B) or pulse pressure (PP-B). Methods In a community-based population of 1014 healthy participants, SBP-C and PP-C were estimated using carotid tonometry, and 24-h systolic (SBP-24 h) and pulse pressure (PP-24 h) were obtained from 24-h ambulatory blood pressure monitoring. Associations of SBP-B, PP-B, SBP-C, PP-C, SBP-24 h, and PP-24 h with all-cause and cardiovascular mortalities over a median follow-up of 15 years were examined by Cox regression analysis. Results In multivariate analyses accounting for age, sex, BMI, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein cholesterol ratio, only PP-C (hazard ratio 1.16, 95% confidence interval 1.01–1.32, per one standard deviation increment) was significantly predictive of all-cause mortality, whereas all but PP-B were significantly predictive of cardiovascular mortality. When SBP-B was simultaneously included in the models, SBP-24 h (2.01, 1.42–2.85) and SBP-C (1.71, 1.21–2.40) remained significantly predictive of cardiovascular mortality. When SBP-C was simultaneously included in the models, SBP-24 h (1.71, 1.16–2.52) remained significantly predictive of cardiovascular mortality. Conclusion Office central blood pressure is more valuable than office peripheral blood pressure in the prediction of all-cause and cardiovascular mortalities. Out-of-office ambulatory peripheral blood pressure (SBP-24 h) may be superior to central blood pressure in the prediction of cardiovascular mortality, but PP-C may better predict all-cause mortality than SBP-24 h or PP-24 h.

Derivation and Validation of Diagnostic Thresholds for Central Blood Pressure Measurements Based on Long-Term Cardiovascular Risks

OBJECTIVESnThis study sought to derive and validate outcome-driven thresholds of central blood pressure (CBP) for diagnosing hypertension.nnnBACKGROUNDnCurrent guidelines for managing patients with hypertension mainly rely on blood pressure (BP) measured at brachial arteries (cuff BP). However, BP measured at the central aorta (central BP [CBP]) may be a better prognostic factor for predicting future cardiovascular events than cuff BP.nnnMETHODSnIn a derivation cohort (1,272 individuals and a median follow-up of 15 years), we determined diagnostic thresholds for CBP by using current guideline-endorsed cutoffs for cuff BP with a bootstrapping (resampling by drawing randomly with replacement) and an approximation method. To evaluate the discriminatory power in predicting cardiovascular outcomes, the derived thresholds were tested in a validation cohort (2,501 individuals with median follow-up of 10 years).nnnRESULTSnThe 2 analyses yielded similar diagnostic thresholds for CBP. After rounding, systolic/diastolic threshold was 110/80 mm Hg for optimal BP and 130/90 mm Hg for hypertension. Compared with optimal BP, the risk of cardiovascular mortality increased significantly in subjects with hypertension (hazard ratio: 3.08, 95% confidence interval: 1.05 to 9.05). Of the multivariate Cox proportional hazards model, incorporation of a dichotomous variable by defining hypertension as CBP ≥ 130/90 mm Hg was associated with the largest contribution to the predictive power.nnnCONCLUSIONSnCBP of 130/90 mm Hg was determined to be the cutoff limit for normality and was characterized by a greater discriminatory power for long-term events in our validation cohort. This report represents an important step toward the application of the CBP concept in clinical practice.

2015 Guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the Management of Hypertension

It has been almost 5 years since the publication of the 2010 hypertension guidelines of the Taiwan Society of Cardiology (TSOC). There is new evidence regarding the management of hypertension, including randomized controlled trials, non-randomized trials, post-hoc analyses, subgroup analyses, retrospective studies, cohort studies, and registries. More recently, the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) published joint hypertension guidelines in 2013. The panel members who were appointed to the Eighth Joint National Committee (JNC) also published the 2014 JNC report. Blood pressure (BP) targets have been changed; in particular, such targets have been loosened in high risk patients. The Executive Board members of TSOC and the Taiwan Hypertension Society (THS) aimed to review updated information about the management of hypertension to publish an updated hypertension guideline in Taiwan. We recognized that hypertension is the most important risk factor for global disease burden. Management of hypertension is especially important in Asia where the prevalence rate grows faster than other parts of the world. In most countries in East Asia, stroke surpassed coronary heart disease (CHD) in causing premature death. A diagnostic algorithm was proposed, emphasizing the importance of home BP monitoring and ambulatory BP monitoring for better detection of night time hypertension, early morning hypertension, white-coat hypertension, and masked hypertension. We disagreed with the ESH/ESH joint hypertension guidelines suggestion to loosen BP targets to <140/90xa0mmHg for all patients. We strongly disagree with the suggestion by the 2014 JNC report to raise the BP target to <150/90xa0mmHg for patients between 60-80 years of age. For patients with diabetes, CHD, chronic kidney disease who have proteinuria, and those who arexa0receiving antithrombotic therapy for stroke prevention, we propose BP targets of <130/80xa0mmHg in our guidelines. BP targets arexa0<140/90xa0mmHg for all other patient groups, except for patients ≥80 years of age in whom a BP target of <150/90xa0mmHg would be optimal. For the management of hypertension, we proposed a treatment algorithm, starting with life style modification (LSM) including S-ABCDE (Sodium restriction, Alcohol limitation, Body weight reduction, Cigarette smoke cessation, Diet adaptation, and Exercise adoption). We emphasized a low-salt strategy instead of a no-salt strategy, and that excessively aggressive sodium restriction to <2.0xa0gram/day may be harmful. When drug therapy is considered, a strategy called PROCEED was suggested (Previous experience, Risk factors, Organ damage, Contraindications or unfavorable conditions, Experts or doctors judgment, Expenses or cost, and Delivery and compliance issue). To predict drug effects in lowering BP, we proposed the Rule of 10 and Rule of 5. With a standard dose of any one of the 5 major classes of anti-hypertensive agents, one can anticipate approximately a 10-mmHg decrease in systolic BP (SBP) (Rule of 10) and a 5-mmHg decrease in diastolic BP (DBP) (Rule of 5). When doses of the same drug are doubled, there is only a 2-mmHg incremental decrease in SBP and a 1-mmHg incremental decrease in DBP. Preferably, when 2 drugs with different mechanisms are to be taken together, the decrease in BP is the sum of the decrease of the individual agents (approximately 20xa0mmHg in SBP and 10xa0mmHg in DBP). Early combination therapy, especially single-pill combination (SPC), is recommended. When patients initial treatment cannot get BP to targeted goals, we have proposed an adjustment algorithm, AT GOALs (Adherence, Timing of administration, Greater doses, Other classes of drugs, Alternative combination or SPC, and LSMxa0+xa0Laboratory tests). Treatment of hypertension in special conditions, including treatment of resistant hypertension, hypertension in women, and perioperative management of hypertension, were also mentioned. The TSOC/THS hypertension guidelines provide the most updated information available in the management of hypertension. The guidelines are not mandatory, and members of the task force fully realize that treatment of hypertension should be individualized to address each patients circumstances. Ultimately, the decision of the physician decision remains of the utmost importance in hypertension management.

White Coat Hypertension Is More Risky Than Prehypertension Important Role of Arterial Wave Reflections

Arterial aging may link cardiovascular risk to white coat hypertension (WCH). The aims of the present study were to investigate the role of arterial aging in the white coat effect, defined as the difference between office and 24-hour ambulatory systolic blood pressures, and to compare WCH with prehypertension (PH) with respect to target organ damage and long-term cardiovascular mortality. A total of 1257 never-been-treated volunteer subjects from a community-based survey were studied. WCH and PH were defined by office and 24-hour ambulatory blood pressures. Left ventricular mass index, carotid intima-media thickness, estimated glomerular filtration rate, carotid-femoral pulse wave velocity, carotid augmentation index, amplitude of the reflection pressure wave, and 15-year cardiovascular mortality were determined. Subjects with WCH were significantly older and had greater body mass index, blood pressure values, intima-media thickness, carotid-femoral pulse wave velocity, augmentation index, amplitude of the backward pressure wave, and a lower estimated glomerular filtration rate than PH. Amplitude of the backward pressure wave was the most important independent correlate of the white coat effect in multivariate analysis (model r 2=0.451; partial r 2/model r 2=90.5%). WCH had significantly greater cardiovascular mortality than PH (hazard ratio, 2.94; 95% confidence interval, 1.09–7.91), after accounting for age, sex, body mass index, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein-cholesterol ratio. Further adjustment of the model for amplitude of the backward pressure wave eliminated the statistical significance of the WCH effect. In conclusion, the white coat effect is mainly caused by arterial aging. WCH carries higher risk for cardiovascular mortality than PH, probably via enhanced wave reflections that accompany arterial aging.nn# Novelty and Significance {#article-title-40}Arterial aging may link cardiovascular risk to white coat hypertension (WCH). The aims of the present study were to investigate the role of arterial aging in the white coat effect, defined as the difference between office and 24-hour ambulatory systolic blood pressures, and to compare WCH with prehypertension (PH) with respect to target organ damage and long-term cardiovascular mortality. A total of 1257 never-been-treated volunteer subjects from a community-based survey were studied. WCH and PH were defined by office and 24-hour ambulatory blood pressures. Left ventricular mass index, carotid intima-media thickness, estimated glomerular filtration rate, carotid-femoral pulse wave velocity, carotid augmentation index, amplitude of the reflection pressure wave, and 15-year cardiovascular mortality were determined. Subjects with WCH were significantly older and had greater body mass index, blood pressure values, intima-media thickness, carotid-femoral pulse wave velocity, augmentation index, amplitude of the backward pressure wave, and a lower estimated glomerular filtration rate than PH. Amplitude of the backward pressure wave was the most important independent correlate of the white coat effect in multivariate analysis (model r 2=0.451; partial r 2/model r 2=90.5%). WCH had significantly greater cardiovascular mortality than PH (hazard ratio, 2.94; 95% confidence interval, 1.09–7.91), after accounting for age, sex, body mass index, smoking, fasting plasma glucose, and total cholesterol/high-density lipoprotein-cholesterol ratio. Further adjustment of the model for amplitude of the backward pressure wave eliminated the statistical significance of the WCH effect. In conclusion, the white coat effect is mainly caused by arterial aging. WCH carries higher risk for cardiovascular mortality than PH, probably via enhanced wave reflections that accompany arterial aging.

Associations of serum uric acid levels with arterial wave reflections and central systolic blood pressure

BACKGROUNDnUric acid may be involved in the pathogenesis of hypertension. We investigated the roles of four major hemodynamic parameters of blood pressure, including arterial stiffness, wave reflections, cardiac output (CO), and total peripheral resistance (TPR), in the association between uric acid and central systolic blood pressure (SBP-c).nnnMETHODSnA sample of 1303 normotensive and untreated hypertensive Taiwanese participants (595 women, aged 30-79 years) was drawn from a community-based survey. Study subjects baseline characteristics, biochemical parameters, carotid-femoral pulse wave velocity (cf-PWV), amplitude of the backward pressure wave decomposed from a calibrated tonometry-derived carotid pressure waveform (Pb), CO, TPR, and SBP-c were analyzed.nnnRESULTSnIn multi-variate analyses adjusted for age, waist circumference, body mass index, creatinine, total cholesterol, smoking, and heart rate, uric acid significantly correlated with Pb and cf-PWV in men, and Pb and TPR in women. The correlation between uric acid and Pb remained significant in men and women when cf-PWV was further adjusted. In the final multi-variate prediction model (model r(2)=0.839) for SBP-c, the significant independent variables included uric acid (partial r(2)=0.005), Pb (partial r(2)=0.651), cf-PWV (partial r(2)=0.005), CO (partial r(2)=0.062), TPR (partial r(2)=0.021), with adjustment for age, sex, waist circumference, body mass index, creatinine, total cholesterol, smoking, and heart rate.nnnCONCLUSIONSnUric acid was significantly independently associated with wave reflections, which is the dominant determinant of SBP-c. Uric acid was also significantly associated with SBP-c independently of the major hemodynamic parameters.

Patient-Specific Oscillometric Blood Pressure Measurement

Objective: Most automatic cuff blood pressure (BP) measurement devices are based on oscillometry. These devices estimate BP from the envelopes of the cuff pressure oscillations using fixed ratios. The values of the fixed ratios represent population averages, so the devices may only be accurate in subjects with normal BP levels. The objective was to develop and demonstrate the validity of a patient-specific oscillometric BP measurement method. Methods: The idea of the developed method was to represent the cuff pressure oscillation envelopes with a physiologic model, and then estimate the patient-specific parameters of the model, which includes BP levels, by optimally fitting it to the envelopes. The method was investigated against gold standard reference BP measurements from 57 patients with widely varying pulse pressures. A portion of the data was used to optimize the patient-specific method and a fixed-ratio method, while the remaining data were used to test these methods and a current office device. Results: The patient-specific method yielded BP root-mean-square-errors ranging from 6.0 to 9.3 mmHg. On an average, these errors were nearly 40% lower than the errors of each existing method. Conclusion: The patient-specific method may improve automatic cuff BP measurement accuracy. Significance: A patient-specific oscillometric BP measurement method was proposed and shown to be more accurate than the conventional method and a current device.

Hypoglycemia and risk of vascular events and mortality: a systematic review and meta-analysis

AbstractAimsnHypoglycemia has been associated with adverse outcomes in patients with diabetes and critical illness. However, such associations in these populations have not been systematically examined.MethodsWe conducted a systematic review and meta-analysis of longitudinal follow-up cohort studies to investigate the associations between hypoglycemia and various adverse outcomes.nResultsAfter removing duplicates and critically appraising all screened citations, a total of 19 eligible studies were included. As demonstrated by random-effects meta-analysis, hypoglycemia was strongly associated with a higher risk of adverse events (HR 1.90, 95xa0% CI 1.63–2.20; Pxa0<xa00.001). Comparable risk ratios were shown in prespecified stratified analyses investigating above association for different study endpoints, in patients with or without critical illness, in patients with and without diabetes (from 1.47 to 3.31; p for interaction or heterogeneity >0.1). Additionally, a dose-dependent relationship between the severity of hypoglycemia and adverse vascular events and mortality (HR for mild hypoglycemia: 1.68, 95xa0% CI 1.25–2.26; Pxa0<xa00.001 and HR for severe hypoglycemia: 2.33, 95xa0% CI 2.07–2.61; Pxa0<xa00.001; p for trend 0.02) was observed. Suggested by a bias analysis, the above observations were unlikely to have resulted from unmeasured confounding parameters.ConclusionsThis is the first study demonstrating that hypoglycemia was associated with comparable risk ratios in different study populations and various study endpoints, and a trend of a dose-dependent relationship between hypoglycemia severity and adverse events. The findings of this systematic review support the speculation that hypoglycemia is a risk factor for adverse vascular events and mortality.

Estimation of Pulse Transit Time as a Function of Blood Pressure Using a Nonlinear Arterial Tube-Load Model

Objective: pulse transit time (PTT) varies with blood pressure (BP) throughout the cardiac cycle, yet, because of wave reflection, only one PTT value at the diastolic BP level is conventionally estimated from proximal and distal BP waveforms. The objective was to establish a technique to estimate multiple PTT values at different BP levels in the cardiac cycle. Methods: a technique was developed for estimating PTT as a function of BP (to indicate the PTT value for every BP level) from proximal and distal BP waveforms. First, a mathematical transformation from one waveform to the other is defined in terms of the parameters of a nonlinear arterial tube-load model accounting for BP-dependent arterial compliance and wave reflection. Then, the parameters are estimated by optimally fitting the waveforms to each other via the model-based transformation. Finally, PTT as a function of BP is specified by the parameters. The technique was assessed in animals and patients in several ways including the ability of its estimated PTT-BP function to serve as a subject-specific curve for calibrating PTT to BP. Results: the calibration curve derived by the technique during a baseline period yielded bias and precision errors in mean BP of 5.1 ± 0.9 and 6.6 ± 1.0 mmHg, respectively, during hemodynamic interventions that varied mean BP widely. Conclusion: the new technique may permit, for the first time, estimation of PTT values throughout the cardiac cycle from proximal and distal waveforms. Significance: the technique could potentially be applied to improve arterial stiffness monitoring and help realize cuff-less BP monitoring.