Sleep Duration as a Risk Factor for Cardiovascular Disease- a Review of the Recent Literature

Sleep loss is a common condition in developed countries, with evidence showing that people in Western countries are sleeping on average only 6.8 hour (hr) per night, 1.5 hr less than a century ago. Although the effects of sleep deprivation on our organs have been obscure, recent epidemiological studies have revealed relationships between sleep deprivation and hypertension (HT), coronary heart disease (CHD), and diabetes mellitus (DM). This review article summarizes the literature on these relationships. Because sleep deprivation increases sympathetic nervous system activity, this increased activity serves as a common pathophysiology for HT and DM. Adequate sleep duration may be important for preventing cardiovascular diseases in modern society

A Case of Syncope Induced in the Supine Position

We experienced a reproducible supine syncope followed by upper abdominal pain. A 66-year-old man was transferred to our hospital after an episode of syncope during sleep. He had a history of acute pancreatitis, diabetes, hypertension, and dyslipidemia, but no history of presyncopal attack. One night, his wife noticed he was snoring abnormally in bed, and he did not respond to her voice until after she tried many times to wake him. The same attack was reproduced three times in the same situation. One of the attacks was recorded under a continuous ECG and radial tonometry. In this case, a presyncopal attack and a sense of ill-feeling were provoked by the patient lying in a prolonged supine position. He was eventually diagnosed as metastatic liver tumor 5 months after the first attack. Because few cases of syncopal attack have been reported in the supine position, its underlying mechanisms deserve consideration

Earthquake-Induced Potentiation of Acute Risk Factors in Hypertensive Elderly Patients: Possible Triggering of Cardiovascular Events After a Major Earthquake

AbstractObjectives. We sought to investigate the potentiation of acute risk factors after the Hanshin-Awaji earthquake (7.2 on the Richter scale).Background. The frequency of cardiovascular events increases just after a major earthquake, but the causative factors have not been fully investigated.Methods. We studied the changes in cardiovascular risk factors in 42 elderly outpatients with well-controlled hypertension living near the epicenter (Awaji-Hokudan districts) 7 to 14 days after the earthquake when the major felt-aftershocks persisted. They all experienced the highest stress grading of 6 (catastrophic stress) according to the DSM-III-R. To study the hemostatic profile and endothelial cell state, we measured the blood pressure (BP), hematocrit and lipid profiles as well as fibrinogen, a marker of fibrin turnover (d-dimer), fibrinolytic factors (plasmin-alpha2–plasmin inhibitor complex [PIC], tissue-type plasminogen activator [t-PA] antigen and t-PA inhibitor [PAI] activity) and an endothelial cell-derived marker (von Willebrand factor [vWF]).Results. Systolic and diastolic blood pressures and other variables increased after the earthquake. Before and after the earthquake, the median (25th to 75th percentiles) systolic BP was 152 (range 142 to 164) and 170 mm Hg (range 161 to 178), respectively (p < 0.0001), and the diastolic BP was 83 (range 79 to 88) and 91 mm Hg (range 84 to 96), respectively (p < 0.0001). Of blood viscosity determinants, hematocrit was 38.1% (range 40.7% to 35.9%) and 39.7% (range 42.9% to 38.3%), respectively (p < 0.001), and fibrinogen 316 (range 272 to 360) and 335 mg/dl (range 307 to 391), respectively (p < 0.05). Von Willebrand factor was 128% (range 74% to 148%) and 148% (range 100% to 178%), respectively (p < 0.01); d-dimer was 410 (range 285 to 633) and 560 ng/ml (range 391 to 888), respectively (p < 0.0001); and PIC was 0.74 (range 0.58 to 0.91) and 0.75 μg/ml (range 0.58 to 1.1), respectively (p < 0.05). In contrast, lipid profiles did not change after the quake. When the patients were classified into the high stress and moderate stress groups according to the degrees of damage to their house and injury to family members, the levels of fibrinogen, vWF, PIC and t-PA antigen were increased only in the former group, whereas BP, hematocrit and d-dimer levels were increased in both groups. These abnormalities of acute risk factors, except for vWF, were transient and decreased to prequake levels by 4 to 6 months after the quake.Conclusions. Earthquake-induced stress seems to induce transient increases in BP, blood viscosity determinants and fibrin turnover and to prolong endothelial cell stimulation. The potentiation of these acute risk factors might contribute to the occurrence of cardiovascular events just after a major earthquake in elderly subjects with hypertension.(J Am Coll Cardiol 1997;29:926–33)© 1997 by the American College of Cardiolog

Role of neprilysin inhibitor combinations in hypertension: insights from hypertension and heart failure trials

Neprilysin is a neutral endopeptidase and its inhibition increases bioavailability of natriuretic peptides, bradykinin, and substance P, resulting in natriuretic, vasodilatatory, and anti-proliferative effects. In concert, these effects are prone to produce a powerful ventricular unloading and antihypertensive response. LCZ696 (Valsartan/sacubitril) is a first-in-class angiotensin II-receptor neprilysin inhibitor. LCZ696 is a novel drug not only for the treatment of heart failure but it is also likely to be a useful antihypertensive drug and may have a preferential effect on systolic pressure. This review discusses (i) the mechanism of action, pharmacokinetics, and pharmacodynamics of this novel drug, (ii) the efficacy, safety, and tolerability of LCZ696 in treatment of hypertension from the available trials, (iii) evidence from other contemporary trials on combined Neprilysin inhibitors, (iv) future trials and areas of research to identify hypertensive patient populations that would most benefit from LCZ69

Cardiac sarcoidosis, the complete atrioventricular block of which was completely recovered by intravenous steroid pulse therapy

AbstractAtrioventricular block (AVB) in individuals with cardiac sarcoidosis (CS) is one of the major complications caused by inflammation of the conducting system of the heart, as a sign of worse prognosis. We report the case of a 53-year-old Japanese woman whose electrocardiogram showed complete AVB by the clinical diagnosis of CS. We administered intravenous methylpredonisolone (1g/day) for 3 days. On the second day of steroid pulse therapy, the complete AVB improved to sinus rhythm of 1st degree AVB and complete right bundle branch block. Normal sinus rhythm was then observed after oral steroid therapy. These results suggest that in cases of complete AVB, steroid pulse therapy with a strong anti-inflammatory effect may be recommended first.<Learning objective: This case illustrates a typical case of CS with complete AVB, but the cardiac contraction was normal. In this setting, steroid pulse therapy may be effective when (1) the active inflammation of the conduction system can be suppressed by steroid pulse therapy; (2) the time to start steroid therapy is short enough to recover.

Study of Sustained Blood Pressure-Lowering Effect of Azelnidipine Guided by Self-Measured Morning and Evening Home Blood Pressure: Subgroup Analysis of the At-HOME Study

BACKGROUND: Morning hypertension is a risk factor for cardiovascular and cerebrovascular events, and consequently diagnosis and control of morning hypertension are considered very important. We previously reported the results of the Azelnidipine Treatment for Hypertension Open-label Monitoring in the Early morning (At-HOME) Study, which indicated that azelnidipine effectively controlled morning hypertension. OBJECTIVES: The objective of this At-HOME subgroup analysis was to evaluate the sustained blood pressure (BP)-lowering effect of azelnidipine, using mean morning and evening systolic BP [ME average] and morning systolic BP minus evening systolic BP (ME difference). METHODS: We analyzed the self-measured home BP data (measured in the morning and at bedtime) from this 16-week prospective observational study to clarify the effect of morning dosing of azelnidipine (mean [± standard deviation] maximum dose 14.3 ± 3.6 mg/day). A subgroup of patients from the At-HOME Study who had an evening home BP measurement within 28 days prior to the baseline date were used for efficacy analysis (n = 2,546; mean age, 65.1 years; female, 53.6 %). RESULTS: Home systolic BP/diastolic BP levels in the morning and evening were significantly lowered (p < 0.0001) by −19.4 ± 17.1/−10.3 ± 10.6 and −16.9 ± 17.0/−9.4 ± 10.6 mmHg, respectively. Home pulse rates in the morning and evening were also significantly lowered (p < 0.0001) by −3.5 ± 7.8 and −3.5 ± 7.3 beats/min, respectively. At baseline, patients whose ME average was ≥135 mmHg and whose ME difference was ≥15 mmHg (defined as morning-predominant hypertension) accounted for 20.4 % of the study population. However, at the end of the study, the number of such patients was significantly reduced to 7.9 % (p < 0.0001). Patients whose ME average was ≥135 mmHg and whose ME difference was <15 mmHg (defined as sustained hypertension) accounted for 71.1 % of the study population at baseline. This was reduced significantly to 42.8 % at the end of the study (p < 0.0001). ME average decreased significantly from 153.8 ± 15.5 mmHg to 135.6 ± 11.9 mmHg, and ME difference also decreased significantly from 6.7 ± 13.1 mmHg to 4.7 ± 10.8 mmHg (both p < 0.0001). CONCLUSION: These results suggest that azelnidipine improved morning hypertension with its sustained BP-lowering effect. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40268-013-0007-7) contains supplementary material, which is available to authorized users

Night Time Blood Pressure Variability Is a Strong Predictor for Cardiovascular Events in Patients With Type 2 Diabetes

Background: We aimed this study to test the hypothesis that short-term blood pressure (BP) variability and abnormal patterns of diurnal BP variation, evaluated by ambulatory BP (ABP), predicts risk of incident cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM). Methods: ABP monitoring (ABPM) was performed in 300 patients with uncomplicated T2DM without known CVD and without BP medications, who were followed for 54 ± 20 months. The relationships of different measures of BP variability, the presence of abnormal patterns of diurnal BP variation (nondipper, riser, or morning BP surge) and the standard deviations of awake and asleep ABP were determined. Cox proportional hazards models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) before and after controlling for various covariates. Results: The mean age was 67.8 ± 9.6 years, 48% were male, 253 (84%) had a diagnosis of hypertension, and the mean of the standard deviations of awake systolic BP/diastolic BP (SBP/DBP) were 18 ± 6/11 ± 4 mm Hg, and those of sleep SBP/DBP were 13 ± 5/9 ± 3 mm Hg. During follow-up, there were 29 cardiovascular events. In multivariable analyses, the standard deviations of sleep SBP (HR = 1.08; 95% CI, 1.01–1.16, P < 0.05) and sleep DBP (HR = 1.13; 1.04–1.23, P < 0.01) were independently associated with incident CVD. Neither the nondipper and riser patterns nor the morning BP surge were associated with incident CVD events independently of clinic and 24-h BP levels. Conclusions: Abnormal diurnal BP variation was not a predictor of CVD in patients with T2DM. Night time BP variability was an independent predictor of future incidence of CVD, suggesting that this measure could reflect pathophysiology of T2DM

Nocturnal nondipping of heart rate predicts cardiovascular events in hypertensive patients

Objective: It has not been established whether nocturnal nondipping of heart rate (HR) predicts future cardiovascular disease (CVD). We performed this study to test the hypothesis that nocturnal nondipping of HR predicts the risk of incident CVD independent of nocturnal blood pressure dipping pattern. Methods: Ambulatory blood pressure monitoring was performed in 457 uncomplicated patients, who were being treated or evaluated for hypertension. They were followed for an average of 72 ± 26 months. Nondipping HR was defined as a night/day HR ratio greater than 0.90. We chose two outcomes for this analysis: CVD events (defined as stroke, myocardial infarction, or sudden cardiac death) and all-cause mortality. Cox regression analyses (stepwise method) were used to estimate hazard ratios and their 95% confidence interval after adjusting for covariates. Results: In univariate analysis, increased sleep HR and nondipping of HR were associated with increased risk of CVD and all-cause mortality, but awake HR was not. In multivariable analyses, HR nondipping status significantly predicted an increased risk of CVD events (hazard ratio, 2.37; 95% confidence interval, 1.22–4.62; P = 0.01), but not for all-cause mortality. Increased 24-h HR was significantly associated with increased risk of all-cause mortality (hazard ratio, 1.67; 95% confidence interval, 1.11–2.51; P = 0.01). Conclusion: The risk of future CVD was shown to be 2.4 times higher in those whose HR does not exhibit the typical nocturnal decline. The relationship was independent of nondipping of SBP and was not dependent on diabetes status or blood pressure level

Ambulatory Blood Pressure Is a Better Marker Than Clinic Blood Pressure in Predicting Cardiovascular Events in Patients With/Without Type 2 Diabetes

Background - The prognostic significance of ambulatory blood pressure (ABP) has not been established in patients with type 2 diabetes (T2DM). Methods - In order to clarify the impact of ABP on cardiovascular prognosis in patients with or without T2DM, we performed ABP monitoring (ABPM) in 1,268 subjects recruited from nine sites in Japan, who were being evaluated for hypertension. The mean age of the patients was 70.4 ± 9.9 years, and 301 of them had diabetes. The patients were followed up for 50 ± 23 months. We investigated the relation between incidence of cardiovascular diseases (CVDs) and different measures of ABP, including three categories of awake systolic blood pressure (SBP 150 mm Hg), sleep SBP (135 mm Hg), and dipping trends in nocturnal blood pressure (BP) (dippers, nondippers, and risers). Cox regression models were used in order to control for classic risk factors. Results - Higher awake and sleep SBPs predicted higher incidence of CVD in patients with and without diabetes. In multivariable analyses, elevated SBPs while awake and asleep predicted increased risk of CVD more accurately than clinic BP did, in both groups of patients. The relationships between ABP level and CVD were similar in both groups. In Kaplan–Meier analyses, the incidence of CVD in nondippers was similar to that in dippers, but risers experienced the highest risk of CVD in both groups (P < 0.01). The riser pattern was associated with a ∼150% increase in risk of CVD, in both groups. Conclusions - These findings suggest that ABPM is a better predictor of cardiovascular risk than clinic BP, and that this holds true for patients with or without T2DM

Central Glucagon-like Peptide-1 Receptor Signaling via Brainstem Catecholamine Neurons Counteracts Hypertension in Spontaneously Hypertensive Rats

Glucagon-like peptide-1 receptor (GLP-1R) agonists, widely used to treat type 2 diabetes, reduce blood pressure (BP) in hypertensive patients. Whether this action involves central mechanisms is unknown. We here report that repeated lateral ventricular (LV) injection of GLP-1R agonist, liraglutide, once daily for 15 days counteracted the development of hypertension in spontaneously hypertensive rats (SHR). In parallel, it suppressed urinary norepinephrine excretion, and induced c-Fos expressions in the area postrema (AP) and nucleus tractus solitarius (NTS) of brainstem including the NTS neurons immunoreactive to dopamine beta-hydroxylase (DBH). Acute administration of liraglutide into fourth ventricle, the area with easy access to the AP and NTS, transiently decreased BP in SHR and this effect was attenuated after lesion of NTS DBH neurons with anti-DBH conjugated to saporin (anti-DBH-SAP). In anti-DBH-SAP injected SHR, the antihypertensive effect of repeated LV injection of liraglutide for 14 days was also attenuated. These findings demonstrate that the central GLP-1R signaling via NTS DBH neurons counteracts the development of hypertension in SHR, accompanied by attenuated sympathetic nerve activity