Search

This study investigates the relationship of neutrophil-lymphocyte ratio (NLR) with the risk of all-cause and cardiovascular mortality in patients with cardiovascular disease. The data for this analysis came from 2239 participants with cardiovascular disease of the National Health and Nutrition Examination Survey conducted between 1999-2018. The optimal cutoff point for NLR was determined using maximally selected rank statistics. Survival analysis was performed using Cox regression models to assess the impact of NLR on the risk of all-cause mortality and cardiovascular mortality. Restricted cubic spline was used to visualize the association of NLR with mortality risk. Subgroup analysis was performed to examine the relationship between NLR and mortality within subgroups based on age, sex, diabetes and hypertension. During a median follow-up period of 6.7 (IQR, 3.3-10.9) years, 992 all-cause deaths occurred, including 381 cardiovascular deaths. Our study revealed that NLR is a risk factor for all-cause mortality (HR: 1.15 95%Cl: 1.11 ~ 1.19) and cardiovascular mortality (HR: 1.14 95%Cl: 1.08 ~ 1.2) among patients with cardiovascular disease. The restricted cubic spline regression analysis showed a non-linear association between NLR and all-cause mortality (p < 0.05 for nonlinearity) in cardiovascular patients. This association remained robust in subgroup analyses stratified by age, sex, diabetes, and hypertension. Conclusion NLR stands as a significant risk factor for both all-cause and cardiovascular mortality among patients with cardiovascular disease., (© 2024. The Author(s).)

Evidence on the association between meeting both aerobic physical activity (PA) and muscle-strengthening activity (MSA) guidelines with mortality in individuals with hypertension is scarce. We included 34,990 adults from the 2007 to 2013 Korea National Health and Nutrition Examination Survey, linking mortality follow-up data until 2019. Adherence to PA guidelines was assessed based on the current PA guidelines using a self-reported questionnaire and categorized as follows: meeting MSA only, aerobic PA only, both MSA and aerobic PA, or neither. Associations of hypertension and adherence to PA guidelines with all-cause and cardiovascular disease (CVD) mortality were examined using Cox proportional hazard models. Over 9.2 years, 1948 participants died from any cause and 419 from CVD. Meeting both PA guidelines was associated with the lowest risk of all-cause and CVD mortalities in the total sample regardless of hypertension status. In individuals with hypertension, meeting aerobic PA guidelines only had a 24% lower risk of both all-cause and CVD mortality, and meeting both PA guidelines further reduced risks by 40% and 43%, respectively; however, meeting MSA guidelines only was not associated with either all-cause or CVD mortality. In individuals without hypertension, only meeting both MSA and aerobic PA guidelines, but not meeting either MSA or aerobic PA guidelines, showed reduced risk of CVD mortality. In Korean population, non-hypertensive individuals who met both guidelines had a lower risk of CVD mortality. However, hypertensive individuals showed a reduced risk of both all-cause and CVD mortality when meeting aerobic PA or both guidelines, but not MSA alone., (© 2024. The Author(s).)

In prior research related to physical activity, researchers have often centered their focus on only a limited number of activities, with little regard for mortality-related outcomes and insufficient focus on outcomes among diabetes patients with hypertension. The National Health and Nutrition Examination Survey was evaluated from 1999-2018 to identify individual with both diabetes and hypertension. These individuals were classified as being physically active or inactive. Comparisons among groups were performed with appropriate statistical tests. In total, this study evaluated data from 6,163 patients with a mean age of 63.18 ± 12.80 years. A total of 50.30% of the participants were male, with 39.86% being non-Hispanic white, 57.17% with a normal body mass index, and 89.20% were insured. Physical activity was significantly negatively correlated with systolic blood pressure in the overall population (p = 0.01) and when specifically focusing on individuals undergoing antihypertensive drug treatment (p = 0.0035). This negative relationship remained intact even following adjustment for age, sex, and ethnicity (p = 0.03). Physical activity was positively correlated with diastolic blood pressure in the overall population of participants (p = 0.002) and when specifically evaluating participants undergoing antihypertensive drug treatment (p = 0.02). All-cause and hypertensive mortality risk levels were significantly higher among individuals classified as being physically inactive (p < 0.0001), and this relationship remained true even with adjustment for age, sex, and ethnicity (p < 0.0001). In conclusion, physical activity is capable of lowering systolic blood pressure and decreasing the incidence of mortality among diabetes patients with hypertension., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Sepsis and hypertension pose significant health risks, yet the optimal mean arterial pressure (MAP) target for resuscitation remains uncertain. This study investigates the association between average MAP (a-MAP) within the initial 24 h of intensive care unit admission and clinical outcomes in patients with sepsis and primary hypertension using the Medical Information Mart for Intensive Care (MIMIC) IV database. Multivariable Cox regression assessed the association between a-MAP and 30-day mortality. Kaplan-Meier and log-rank analyses constructed survival curves, while restricted cubic splines (RCS) illustrated the nonlinear relationship between a-MAP and 30-day mortality. Subgroup analyses ensured robustness. The study involved 8,810 patients. Adjusted hazard ratios for 30-day mortality in the T1 group (< 73 mmHg) and T3 group (≥ 80 mmHg) compared to the T2 group (73-80 mmHg) were 1.25 (95% CI 1.09-1.43, P = 0.001) and 1.44 (95% CI 1.25-1.66, P < 0.001), respectively. RCS revealed a U-shaped relationship (non-linearity: P < 0.001). Kaplan-Meier curves demonstrated significant differences (P < 0.0001). Subgroup analysis showed no significant interactions. Maintaining an a-MAP of 73 to 80 mmHg may be associated with a reduction in 30-day mortality. Further validation through prospective randomized controlled trials is warranted., (© 2024. The Author(s).)

There is scarce evidence of the role of clinic and ambulatory BP indices, as well as blood pressure phenotypes in the prognosis of stroke survivors. We aimed to evaluate the association between ambulatory BP indices and mortality in patients with a previous stroke. Our study was an observational cohort study from individuals included in the Spanish Ambulatory Blood Pressure Registry from March 2004 to December 2014. The Cox model was used to estimate associations between usual clinic and ambulatory BP and mortality, adjusted for confounders and additionally for alternative measures of BP. Two thousand one hundred and eighty-three patients with a previous stroke were included. During a median of 9.2 years, 632 (28.9%) patients died: 236 (10.8%) from cardiovascular causes. In the confounder-adjusted model, clinic systolic BP was not associated with the risk of all-cause or cardiovascular mortality. In contrast, systolic BP indices obtained through ABPM (24 h, day and night) were all associated with all-cause and cardiovascular death. In the simultaneous adjustment of daytime and night-time systolic BP, only night-time systolic BP remained significantly associated with all-cause and cardiovascular death: HR 1.35 (95% CI 01.21-1.51) and 1.44 (1.20-1.72), respectively. For diastolic BP, only night-time BP was associated with all-cause and cardiovascular mortality: HR 1.32 (1.18-1.48) and 1.57 (1.31-1.88), respectively. According to the circadian pattern, a riser pattern was associated with all-cause and cardiovascular mortality: HR 1.49 (1.18-1.87) and 1.70 (1.14-2.52), respectively. In conclusion, in patients who have suffered a stroke, night-time BP is the BP estimate most closely associated with all-cause and cardiovascular mortality., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

How blood pressure variation is associated with frailty and mortality in the elderly: three-years follow-up blood pressure changes in 65+years old patients., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The serum uric acid to serum creatinine ratio (SUA/sCr) is a standardized index of renal function. More importance was attached to the significance of this ratio in the progression of hypertension. While the association between the prognosis of hypertension and SUA/sCr is unknown. Therefore, we aimed to prospectively examine the associations of serum uric acid to serum creatinine ratio and all-cause and CVD mortality in adults with hypertension. Participants with hypertension from NHANES 1999-2018 (n = 15,269) were included. They were stratified by 1 increment of SUA/sCr ratio and categorized into 6 groups as ≤ 4, > 4 to 5, > 5 to 6, > 6 to 7, > 7 to 8, and > 8. The reason for categorization in 6 groups was to analyze the influence of different ratios on outcomes accurately and provide more precise guidance. The sample size is large enough that even if divided into 6 groups, it does not affect the statistical power. The primary outcomes were all-cause and CVD mortality. Weighted multivariable Cox proportional hazards regression models were used to estimate hazard ratio (HRs) of mortality. Restricted cubic spline regression models were utilized to examine dose-response associations between the serum uric acid to serum creatinine ratio and all-cause and CVD mortality. Relatively comprehensive stratified analyses were conducted to confirm the accuracy and stability of the results. There were 15,269 total participants, 49.4% of whom were men, with an average age of 56.6 years. Weighted multivariable Cox proportional hazards regression models demonstrated participants in the lowest group (≤ 4) had the HRs (95% CIs) of 1.43 (1.18, 1.73) for all-cause mortality and 2.8 (1.92, 4.10) for CVD mortality when compared to the reference group. Participants in the highest group (> 8) had the HRs (95% CIs) of 0.47 (0.25, 0.89) for CVD mortality when compared to the reference group. There were progressively lower risks for all-cause and CVD mortality with the SUA/sCr ratio increased (both P trend < 0.01). The SUA/sCr ratio was (P for nonlinearity < 0.01) nonlinearly correlated with all-cause mortality, with inflection points of 6.25. In addition, the restricted cubic splines results indicated that the SUA/sCr ratio (P for nonlinearity = 0.32) showed linear and negative associations with cardiovascular mortality with inflection points of 6.54. The inverse associations between SUA/sCr ratio and all-cause mortality were consistent across all subgroups except for the subgroup of eGFR < 45 ml/min/1.73 m 2 and never smokers (P trend = 0.20 and 0.13, respectively), and the inverse associations between low SUA/sCr ratio and CVD mortality were consistent across all subgroups (P trend < 0.01). Contrary to previous studies, outcomes suggest that lower SUA/sCr ratio was associated with higher risks of all-cause and CVD mortality in adults with hypertension., (© 2024. The Author(s).)

It remains unclear the age-specific associations of risk factors with deaths and mortality burden attributable across age. In a territory-wide retrospective cohort, 1,012,228 adults with hypertension were identified. Comorbidities including diabetes, chronic kidney disease (CKD), cardiovascular disease (CVD), heart failure, and cancer, and risk factors including current smoking and suboptimal control of blood pressure (BP), glucose and low-density lipoprotein cholesterol were defined. Associations of comorbidities/risk factors with all-cause and cause-specific mortality across age groups (18-54, 55-64, 65-74, and ≥75 years) were assessed. Population attributable fractions were also quantified. During a median follow-up of 10.7 years, 244,268 (24.1%) patients died, with pneumonia (7.2%), cancer (5.1%), and CVD (4.2%) being the leading causes. Despite increasing deaths with age, relative risk of mortality related to comorbidities/risk factors decreased with age; similar patterns were found for cause-specific mortality. The assessed risk factors accounted for 24.0% (95% CI 22.5%, 25.4%) deaths, with highest proportion in the youngest group (33.5% [28.1%, 38.5%] in 18-54 years vs 19.4% [17.0%, 21.6%] in ≥75 years). For mortality burden, CKD was the overall leading risk factor (12.7% [12.4%, 12.9%]) with higher proportions in older patients (11.1-13.1% in ≥65 years), while diabetes was the leading risk factor in younger patients (15.9-13.5% in 18-54 years). The association of comorbidities or risk factors with mortality is stronger in younger patients with hypertension, despite lower absolute mortality in young patients than in the elderly. Leading risk factors differed across age, highlighting the importance of targeted and precise risk management., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The evidence regarding the effects of blood pressure changes on older individuals remains inconclusive, and the impact of frailty throughout the life course is not known. We investigated the associations of different change patterns of blood pressure during 3-year intervals with frailty and mortality. Participants included 7335 persons from 2008 to 2014 of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Change in blood pressure was calculated as the difference between follow-up and baseline. Frailty was evaluated using a 40-item frailty index. Mortality status was ascertained up to December 31, 2014. The mean age of participants was 82.6 ± 10.7 years. The optimal blood pressure level (SBP, 130-150 mmHg; DBP, 70-90 mmHg) was associated with the lowest risk of frailty while decreasing follow-up SBP and DBP were significantly correlated with frailty. Lower baseline blood pressure levels (SBP < 130 mmHg; DBP < 70 mmHg) were associated with decreased mortality risk when participants increased their blood pressure to optimal levels during follow-up SBP and DBP (0.78, 0.63-0.98), compared to maintaining a steady low SBP (< 130 mmHg) and DBP (< 70 mmHg). For those with DBP around 70-90 mmHg, decreasing follow-up DBP (< 70 mmHg) was associated with higher mortality (1.23, 1.07-1.42) compared to maintaining stable follow-up DBP (70-90 mmHg). These results remain significant after adjusting for frailty. Optimal blood pressure levels were associated with the lowest risk of frailty. The association between lower blood pressure and increased mortality risk persisted even after accounting for frailty. We used a nationally representative longitudinal cohort study by using 2008-2014 of the Chinese Longitudinal Healthy Longevity in China. Change in blood pressure was calculated as the difference between follow-up and baseline. We investigated the associations of different change patterns of blood pressure during 3-year intervals with frailty and mortality., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Plasma total homocysteine (tHcy) and kidney function are both associated with mortality risk, but the degree to which kidney function modifies the impact of tHcy on mortality remains unknown. This prospective cohort study included a total of 14,225 hypertensive adults. Cox proportional hazard regression was used to analyze the separate and combined association of tHcy and estimated glomerular filtration rate (eGFR) with all-cause and cause-specific mortality. Mediation analysis was conducted to explore the mediating effect of eGFR. During a median follow-up of 4.0 years, 805 deaths were identified, including 397 deaths from cardiovascular disease (CVD). There were significant, positive relationships of tHcy with all-cause mortality (per 5 μmol/L; HR: 1.09; 95% CI: 1.07, 1.11), CVD mortality (HR: 1.11; 95% CI: 1.08, 1.13), and non-CVD mortality (HR: 1.07; 95% CI: 1.04, 1.10). The proportions of eGFR mediating these relationships were 39.1%, 35.7%, and 49.7%, respectively. There were additive interactions between tHcy and eGFR. Compared with those with low tHcy (<15 μmol/L) and high eGFR (≥90 mL·min -1 ·1.73 m -2 ), participants with high tHcy (≥20 μmol/L) and low eGFR (<60 mL·min -1 ·1.73 m -2 ) had the highest risk of all-cause mortality (HR: 4.89; 95% CI: 3.81, 6.28), CVD mortality (HR: 5.80; 95% CI: 4.01, 8.40), and non-CVD mortality (HR: 4.25; 95% CI: 3.02, 5.97). In conclusion, among Chinese hypertensive adults, high tHcy and impaired kidney function were independently and jointly associated with higher risks of all-cause and cause-specific mortality. Importantly, kidney function explained most (nearly 40%) of the increased risk of mortality conferred by high tHcy., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

This study aimed to examine the interaction between diet quality indices (DQIs) and smoking on the incidence of hypertension (HTN), stroke, cardiovascular diseases, and all-cause mortality. We prospectively followed 5720 participants and collected dietary data via a validated food frequency questionnaire to calculate DQI-international (DQI-I) and DQI-revised (DQI-R). Considering an interaction analysis, we classified participants based on diet quality (median: higher/lower) and smoking status. Over 9 years of follow-up, higher diet quality scores were associated with a lower risk of stroke and mortality. While current smokers had a higher risk of stroke and mortality but had a lower risk of developing HTN. Compared to the current smokers with lower diet quality, nonsmokers with higher diet quality according to the DQI-I [HR 0.24; 95% CI (0.08, 0.66)], and DQI-R [HR 0.20; 95% CI (0.07, 0.57)] had a lower risk of stroke. Moreover, the lower risk of mortality was more evident in nonsmokers with higher DQI-I [HR 0.40; 95% CI (0.22-0.75)] and DQI-R scores [HR 0.34; 95% CI (0.18-0.63)] compared to nonsmokers with lower diet quality. While higher DQI-I and DQI-R scores were associated with a lower risk of stroke and mortality, this beneficial effect may be negated by smoking., (© 2024. The Author(s).)

B-type natriuretic peptide (BNP) is a well-established prognostic factor for cardiovascular disorders. However, the association between BNP levels and mortality in patients with acute severe hypertension remains unclear. This study aimed to investigate the association between BNP levels and long-term mortality in patients with acute severe hypertension visiting the emergency department (ED). This retrospective study included patients aged ≥ 18 years who were admitted to the ED between 2016 and 2019 with acute severe hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg). Patients were categorized into tertiles according to BNP levels upon admission to the ED. Of the 3099 patients with acute severe hypertension, 6.4% in the first (lowest) tertile, 24.8% in the second tertile, and 44.4% in the third (highest) tertile of BNP died within 3-years. After adjusting for clinically relevant variables, patients in the second tertile of BNP (adjusted hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.96-3.55), and patients in the third tertile of BNP (adjusted HR 4.18; 95% CI, 3.09-5.64) had a significantly higher risk of 3-year all-cause mortality than those in the first tertile of BNP. Therefore, BNP may be valuable for the initial assessment to identify high-risk patients among those with acute severe hypertension., (© 2022. The Author(s).)

Although postural hypotension (PH) is reportedly associated with mortality in the general population, the prognostic value for heart failure is unclear. This was a post-hoc analysis of FRAGILE-HF, a prospective multicenter observational study focusing on frailty in elderly patients with heart failure. Overall, 730 patients aged ≥ 65 years who were hospitalized with heart failure were enrolled. PH was defined by evaluating seated PH, and was defined as a fall of ≥ 20 mmHg in systolic and/or ≥ 10 mmHg in diastolic blood pressure within 3 min after transition from a supine to sitting position. The study endpoints were all-cause death and heart failure readmission at 1 year. Predictive variables for the presence of PH were also evaluated. PH was observed in 160 patients (21.9%). Patients with PH were more likely than those without PH to be male with a New York Heart Association classification of III/IV. Logistic regression analysis showed that male sex, severe heart failure symptoms, and lack of administration of angiotensin-converting enzyme inhibitors were independently associated with PH. PH was not associated with 1-year mortality, but was associated with a lower incidence of readmission after discharge after adjustment for other covariates. In conclusion, PH was associated with reduced risk of heart failure readmission but not with 1-year mortality in older patients with heart failure., (© 2022. The Author(s).)

This study investigated the outcomes and major adverse cardiovascular events (MACEs) incurred by acute myocardial infarction (AMI) patients comorbiding with hypertension and hyperhomocysteinemia (HHcy) during hospitalization and 1-year follow-up. 648 consecutive AMI patients were divided into four categories: (1) hypertension with Hcy ≥ 15 µmol/L; (2) hypertension with Hcy < 15 µmol/L; (3) no-hypertension with Hcy ≥ 15 µmol/L; (4) no-hypertension with Hcy < 15 µmol/L. Information taken from these case files included gender, past medical history, vital signs, laboratory examination, electrocardiogram, coronary angiography, cardiac ultrasound, and medicine treatment. The primary endpoints were duration of coronary care units (CCU) stay, duration of in-hospital stay, and MACEs during follow-up. Our data show that hypertension and HHcy have a synergistic effect in AMI patients, AMI comorbiding with hypertension and HHcy patients had more severe multi-coronary artery disease and more frequent non-culprit coronary lesions complete clogging, had a higher prevalence of pro-brain natriuretic peptide, and significant decreases in the left ventricular ejection fraction. These patients had significant increases in the duration of CCU stay and in-hospital stay, had significant increase in the rate of MACEs, had significant decreases in the survival rate during follow-up., (© 2021. The Author(s).)

The association between low density lipoprotein cholesterol (LDL-C) and all-cause mortality has been examined in many studies. However, inconsistent results and limitations still exist. We used the 1999-2014 National Health and Nutrition Examination Survey (NHANES) data with 19,034 people to assess the association between LDL-C level and all-cause mortality. All participants were followed up until 2015 except those younger than 18 years old, after excluding those who died within three years of follow-up, a total of 1619 deaths among 19,034 people were included in the analysis. In the age-adjusted model (model 1), it was found that the lowest LDL-C group had a higher risk of all-cause mortality (HR 1.708 [1.432-2.037]) than LDL-C 100-129 mg/dL as a reference group. The crude-adjusted model (model 2) suggests that people with the lowest level of LDL-C had 1.600 (95% CI [1.325-1.932]) times the odds compared with the reference group, after adjusting for age, sex, race, marital status, education level, smoking status, body mass index (BMI). In the fully-adjusted model (model 3), people with the lowest level of LDL-C had 1.373 (95% CI [1.130-1.668]) times the odds compared with the reference group, after additionally adjusting for hypertension, diabetes, cardiovascular disease, cancer based on model 2. The results from restricted cubic spine (RCS) curve showed that when the LDL-C concentration (130 mg/dL) was used as the reference, there is a U-shaped relationship between LDL-C level and all-cause mortality. In conclusion, we found that low level of LDL-C is associated with higher risk of all-cause mortality. The observed association persisted after adjusting for potential confounders. Further studies are warranted to determine the causal relationship between LDL-C level and all-cause mortality., (© 2021. The Author(s).)

Arterial hypertension is a major global health problem. It is the main risk factor for preventable death and the leading cause of premature death in the world. This study aims to describe the changes in hypertension-related mortality in Mexico between 1998 and 2018. Using death certificates and national population public data sets, a total of 335,863 deaths due to hypertension were found in Mexico, disaggregated by sex and age, during the time period covered in this study. An age-period-cohort analysis was conducted to show trends in hypertension mortality rates. Mortality due to hypertension in Mexico affects more women than men. In the most recent cohorts, the risk of dying from hypertension is two times higher in men compared to women. Hypertensive kidney disease is found to be the main underlying cause, with an average increase throughout the period studied. Our results indicate that mortality rates due to hypertension continue to grow and point to an alarming trend of mortality shifting towards younger ages, with sex-based disparities in absolute numbers and in changing trends., (© 2021. The Author(s).)

Hypertension is a chronic disease that has a major health problem over the centuries due to its significant contribution to the global burden. The objective of this study was to examine the association of survival time and longitudinal Systolic Blood Pressure (SBP) measurement and finding potential barrier that affects SBP measurement and the survival time of hypertension patients. The study considered a cohort of 318 hypertension patients who were aged 18 years or older and were under follow-up from January 1, 2012, to February 30, 2020, at Arba Minch General Hospital. To analyze the data we employed linear mixed effect model, Weibull model, and joint modeling approach for longitudinal and survival data. The results from joint model analysis indicate that systolic blood pressure measurement is significantly associated with survival time of hypertension patients. The results from the longitudinal sub-model reveals that alcohol use, Khat intake, smoking tobacco, stages of hypertension diseases, adherence to treatment, related diseases, and family history had statistical significant relationship with mean change in the [Formula: see text] measurement. Furthermore, from the survival sub-model, we found the survival probability of hypertension patients was determined by family history, stages of hypertension disease, related diseases, and smoking tobacco. The analysis suggests that there is a strong association between SBP measurement and survival time of hypertension patients. Thus we recommend aggressive work by all concerned bodies towards awareness creation about the effect of potential barriers., (© 2021. The Author(s).)

Hypertension is a serious public health problem worldwide. MT-1207, chemically named 3-(4-(4-(1H-benzotriazole-1-yl)butyl)piperazine-1-yl) benzisothiazole hydrochloride, is a new chemical entity that has entered into clinical trial as antihypertensive agent in China. In this paper we report the pharmacological profile of MT-1207 regarding its acute, subacute, and long-term effects on hypertensive animal models, and its actions on isolated organs in vitro as well as its molecular targets. Blood pressure (BP) was measured in conscious animals; amlodipine was taken as a positive control drug. We showed that both single dose of MT-1207 (1.25-20 mg/kg, ig) in spontaneously hypertensive rats (SHR) and MT-1207 (0.25-6 mg/kg, ig) in two-kidney one-clip (2K1C) dogs dose-dependently decreased BP. MT-1207 quickly decreased BP within 5 min after administration; the hypotensive effect lasted for 8 and 12 h, respectively, in SHR and 2K1C dogs without reflex increase in heart rate. Multiple doses of MT-1207 (5 mg · kg -1  · d -1 in SHR; 2 mg · kg -1  · d -1 in 2K1C dogs, for 7 days) significantly decreased BP, slightly reduced heart rate, and both of them recovered after withdrawal. Long-term administration of MT-1207 (10 mg · kg -1  · d -1 for 4 months or more time) produced a stable BP reduction, improved baroreflex sensitivity, reduced renal and cardiovascular damage in SHR, and delayed stroke occurrence and death in stroke-prone SHR. In isolated rat aortic rings precontracted by adrenaline, KCl, noradrenaline or 5-hydroxytryptamine (5-HT), MT-1207 (10 -9 -10 -4  M) caused concentration-dependent relaxation. In a panel of enzyme activity or radioligand binding assays of 87 molecular targets, MT-1207 potently inhibited adrenergic α 1A , α 1B , α 1D , and 5-HT 2A receptors with K i  < 1 nM. The antagonism of MT-1207 against these receptors was confirmed in isolated rabbit arteries. We conclude that MT-1207 is a novel and promising single-molecule multitarget agent for hypertension treatment to reduce hypertensive organ damage and stroke mortality.

Stroke is a common cause of death and disability. Allisartan isoproxil (ALL) is a new angiotensin II receptor blocker and a new antihypertensive drug discovered and developed in China. In the present study we investigated the therapeutic effects of ALL in stroke-prone renovascular hypertensive rats (RHR-SP) and the underlying mechanisms. The model rats were generated via two-kidney two-clip (2K2C) surgery, which led to 100% of hypertension, 100% of cerebrovascular damage as well as 100% of mortality 1 year after the surgery. Administration of ALL (30 mg · kg -1  · d -1 in diet, for 55 weeks) significantly decreased stroke-related death and prolonged lifespan in RHR-SP, but the survival ALL-treated RHR-SP remained of hypertension and cardiovascular hypertrophy compared with sham-operated normal controls. In addition to cardiac, and aortic protection, ALL treatment for 10 or 12 weeks significantly reduced cerebrovascular damage incidence and scoring, along with a steady reduction of blood pressure (BP) in RHR-SP. Meanwhile, it significantly decreased serum aldosterone and malondialdehyde levels and cerebral NAD(P)H oxidase expressions in RHR-SP. We conducted 24 h continuous BP recording in conscious freely moving RHR-SP, and found that a single intragastric administration of ALL produced a long hypotensive effect lasting for at least 12 h on systolic BP. Taken together, our results in RHR-SP demonstrate that ALL can be used for stroke prevention via BP reduction and organ protection, with the molecular mechanisms related to inhibition of angiotensin-aldosterone system and oxidative stress. This study also provides a valuable scoring for evaluation of cerebrovascular damage and drug efficacy.

Evidence regarding the relation between SARS-CoV-2 mortality and the underlying medical condition is scarce. We conducted an observational, retrospective study based on Romanian official data about location, age, gender and comorbidities for COVID-19 fatalities. Our findings indicate that males, hypertension, diabetes, obesity and chronic kidney disease were most frequent in the COVID-19 fatalities, that the burden of disease was low, and that the prognosis for 1-year survival probability was high in the sample. Evidence shows that age-dependent pairs of comorbidities could be a negative prognosis factor for the severity of disease for the SARS-CoV 2 infection.

Lifetime risk is an informative estimate to motivate people to change lifestyle behaviors, especially from a younger age, in public health education. The impact of the combination of hypertension and diabetes on the lifetime risk of cardiovascular mortality has not been investigated in Asian populations. A pooled analysis of individual data from nine cohorts was performed. A total of 57,339 Japanese men and women were eligible for the analysis. We used the modified Kaplan-Meier approach and estimated the remaining lifetime risk of cardiovascular mortality starting from the index age of 35 years. Participants were classified into four categories defined by hypertension and diabetes. The lifetime risk was increased in the order of those without either risk, those without hypertension but with diabetes, those with hypertension but without diabetes, and those with both risks. The lifetime risk of cardiovascular mortality at the 35-year index age was as follows: 7.8% in men and 6.2% in women for those without either hypertension or diabetes, 13.2% in men and 9.5% in women for those without hypertension but with diabetes, 17.2% in men and 11.7% in women for those with hypertension but without diabetes, and 19.4% in men and 15% in women for those with both risks. These findings reinforce the need for a life-course perspective in the management of hypertension and diabetes from a younger age.

A shift towards high folate concentration has emerged following folate fortification. However, the association between folate and health outcomes beyond neural tube defects remains inconclusive. To assess the relationship between red blood cell (RBC) folate and the risk of cardiovascular death among hypertensive patients, we analyzed the data of 2,986 adults aged 19 or older with hypertension who participated in the National Health and Nutrition Examination Survey (1991-1994) as the baseline examination and were followed up through December 31, 2010. After 32,743 person-years of follow-up with an average of 11.7 (standard error = 0.03) years, 1192 deaths were recorded with 579 cardiovascular deaths. The median survival time was significantly shorter in adults in the high folate quartile than in patients in the low folate quartile: 11.97 vs. 13.85 years for heart diseases and 13.37 vs. 14.82 years for myocardial infarction deaths. The cardiovascular mortality was 13.04, 16.95, and 26.61/1,000 person-years for the groups with low, intermediate and high folate quartiles, respectively. After adjustment for age, sex and other factors, a J-shaped association emerged. The hazard ratios (HRs) of all cardiovascular deaths in patients with low, intermediate, and high folate quartiles were 1.09 (0.94, 1.27), 1.00 (reference), and 1.44 (1.31, 1.58), respectively. The corresponding HRs of acute myocardial infarction were 1.13 (0.86, 1.50), 1.00, and 2.13 (1.77, 2.57), respectively. The estimates remained significant after adjustment for BMI and medication use. Compared to moderate RBC folate levels, high folate levels were significantly associated with an increased risk of cardiovascular deaths, especially acute myocardial infarction.

In Caucasian and Asian populations, evidence suggests that 24-h blood pressures (BP) are more predictive of long-term cardiovascular events than clinic BP. However, few long-term studies have evaluated the predictive value of 24-h BP phenotypes (24-h, daytime, nighttime) among African Americans (AA). The purpose of this study is to evaluate the added value of 24-h BP phenotypes compared to clinic BP in predicting the subsequent fatal and non-fatal cardiovascular/renal disease events in AA subjects. AA subjects (n = 270) were initially studied between 1994 and 2006 and standardized clinic BP measurements were obtained during screening procedures for a 3-day inpatient clinical study during which 24-h BP measurements were obtained. To assess the subsequent incidence of cardiovascular and renal disease events, follow-up information was obtained and confirmed by review of paper and electronic medical records between 2015 and 2017. During a mean follow-up of 14 ± 4 years, 50 subjects had one or more fatal or non-fatal cardiovascular/renal disease events. After adjustment for covariates, clinic systolic and diastolic BP were strongly associated with cardiovascular/renal disease events and all-cause mortality (p < 0.0001). Twenty-four-hour BP phenotypes conferred a small incremental advantage over clinic BP in predicting cardiovascular/renal events, which was limited to making a difference of one predicted event in 250-1,000 predictions depending on the 24-h BP phenotype. Nocturnal BP was no more predictive than the other 24-h BP phenotypes. In AA, 24-h BP monitoring provides limited added value as a predictor of cardiovascular/renal disease events. Larger studies are needed in AA to confirm these findings.

Methamphetamine use has emerged as a risk factor for intracerebral hemorrhage (ICH). We aim to investigate the clinical characteristics and outcomes of methamphetamine-associated ICH (Meth-ICH) versus Non-Meth-ICH. Patients with ICH between January 2011 and December 2017 were studied. Meth-ICH and Non-Meth-ICH were defined by history of abuse and urine drug screen (UDS). The clinical features of the 2 groups were explored. Among the 677 consecutive patients, 61 (9.0%) were identified as Meth-ICH and 350 as Non-Meth ICH. Meth-ICH was more common in Hispanics (14.6%) and Whites (10.1%) as compared to Asians (1.2%). Patients with Meth-ICH were more often younger (51.2 vs. 62.2 years, p < 0.001), male (77.0% vs. 61.4.0%, p < 0.05), and smokers (44.3% vs. 13.4%, p < 0.001). Non-Meth-ICH was more likely to have history of hypertension (72.61% v. 59%, p < 0.05) or antithrombotic use (10.9% vs. 1.6%, p < 0.05). There was no significant difference in clinical severity, hospital length of stay (LOS), rate of functional independence (29.5% vs. 25.7%, p = 0.534), or mortality (18.0% vs. 24.6%, p = 0.267) between the 2 groups. Methamphetamine use was not an independent predictor of poor outcome. Despite difference in demographics, Meth-ICH is similar to Non-Meth ICH in hospital course and outcome.

Mortality of primary hypertension is high worldwide. Whether untraditional factors exist in modern life and affect the mortality is not well studied. The aim of the study was to evaluate the risk factors for fatality rate of hypertensive men in downtown area. A cross-sectional study was performed on hypertensive men, who were hospitalized into our hospital and lived in eligible urban areas. The characteristics of the patients and factors for the fatality were analyzed and of the risks or the contributors on the status were investigated. 14354 patients were identified. Mean age was 68.9 ± 12.4 year old (y) and dead ones was 75.9 ± 9.5 y. The overall hospitalized fatality was 5.9%, which was increased with age: fatality with 0.7%, 2.2%, 2.9%, 7.1%, 11.1% and 16.6% was for age group ≦ 49 y, 50-59 y, 60-69 y, 70-79 y, 80-89 y and ≧ 90 y respectively. The increased fatality was significantly positively correlated with the incidence of pneumonia, P < 0.05, r = 0.99. Pneumonia was prone to involve in men with older age and severer organ damage by hypertension. Similar to traditional risks such as coronary heart disease and stroke, pneumonia and lung cancer were also significantly associated with the fatality. Odds ratio (95% CI) for pneumonia and lung cancer were 6.18 (4.35-8.78) and 1.55 (1.14-2.11). The study provides evidence that pneumonia and lung cancer are highly associated with fatality of hypertensive men in downtown area, indicating that in order to reduce the fatality of hypertension, these lung diseases should be prevented and treated intensively in modern life.

The role of the direct renin inhibitor aliskiren in hypertension is not fully established and use of aliskiren in diabetic patients is especially controversial. A systematic review investigating both short-term diastolic and systolic blood pressure (DBP and SBP) reduction and long-term cardiovascular outcomes has not been conducted. Therefore, we aimed to fill this gap by investigating BP reduction, major cardiovascular outcomes, and mortality of aliskiren compared to other antihypertensive therapy. We searched PubMed and Embase databases for relevant randomized controlled trials (RCTs). Using a random-effects model, weighted mean difference (WMD) and relative risk (WRR) with 95% confidence interval (CI) were used to measure the effect of aliskiren therapy in the management of hypertension and major cardiovascular outcomes. Thirty seven RCTs with a total of 35,916 patients were included. Aliskiren induced slightly greater DBP and SBP reductions than other antihypertensive agents (WMD -0.77 mmHg, 95% CI [-2.01;0.46 mmHg] and WMD -1.14 mmHg, 95% CI [-2.78;0.50 mmHg], respectively). Aliskiren did not reduce total mortality or cardiovascular death. In patients with diabetes, aliskiren add-on therapy may have the potential to increase total mortality and cardiovascular death (WRR 1.06, 95% CI [0.88;1.28] and WRR 1.09, 95% CI [0.94;1.24], respectively). Despite superior BP-reducing effect, aliskiren is not recommended as first-line treatment in hypertensive patients as it does not reduce mortality and major cardiovascular outcomes. Dual renin-angiotensin-aldosterone system inhibition with aliskiren should be avoided in diabetic patients, while the use of aliskiren monotherapy remains to be investigated.

We examined the association of orthostatic hypertension with all-cause mortality in the active treatment and placebo randomized groups of the Systolic Hypertension in the Elderly Program (SHEP). SHEP was a multicenter, randomized, double-blind, placebo-controlled clinical trial of the effect of chlorthalidone-based antihypertensive treatment on the rate of occurrence of stroke among older persons with isolated systolic hypertension (ISH). Men and women aged 60 years and above with ISH defined by a systolic blood pressure (SBP) of 160 mm Hg or higher and diastolic blood pressure lower than 90 mm Hg were randomized to chlorthalidone-based stepped care therapy or matching placebo. Among 4736 SHEP participants, 4073 had a normal orthostatic response, 203 had orthostatic hypertension, and 438 had orthostatic hypotension. Compared with normal response, orthostatic hypertension was associated with higher all-cause mortality at 4.5 and 17 years in analyses adjusted for age, gender, treatment, SBP, and pulse pressure (PP, HR 1.87, 95% CI 1.30-2.69, p = 0.0007; HR 1.40, 95% CI 1.17-1.68, p = 0.0003, respectively). These associations remained significant after additional adjustment for risk factors and comorbidities (HR 1.43, 95% CI 0.99-0.08, p = 0.0566 at 4.5 years, and HR 1.27, 95% CI 1.06-1.53, p = 0.0096 at 17 years). The increased risk of all-cause mortality associated with orthostatic hypertension was observed in both the active and placebo groups without significant interaction between randomization group and the effect on mortality. Orthostatic hypertension is associated with future mortality risk, is easily detected, and can be used in refining cardiovascular risk assessment.

High systolic blood pressure (SBP) causes cardiovascular disease (CVD) and is associated with mortality from other causes, but conventional multivariably-adjusted results may be confounded. Here we used a son's SBP (>1 million Swedish men) as an instrumental variable for parental SBP and examined associations with parents' cause-specific mortality, avoiding reverse causation. The hazard ratio for CVD mortality per SD (10.80 mmHg) of SBP was 1.49 (95% CI: 1.43, 1.56); SBP was positively associated with coronary heart disease and stroke. SBP was also associated positively with all-cause, diabetes and kidney cancer mortality, and negatively with external causes. Negative associations with respiratory-related mortality were probably confounded by smoking. Hazard ratios for other causes were imprecise or null. Diastolic blood pressure gave similar results to SBP. CVD hazard ratios were intermediate between those from conventional multivariable studies and Mendelian randomization and stronger than those from clinical trials, approximately consistent with an effect of exposure duration on effect sizes. Plots of parental mortality against offspring SBP were approximately linear, supporting calls for lower SBP targets. Results suggest that conventional multivariable analyses of mortality and SBP are not substantially confounded by reverse causation and confirm positive effects of SBP on all-cause, CVD and diabetes mortality.

Renin-angiotensin system (RAS) inhibitors are often used as a first-line treatment for hypertensive patients with diabetes because of purported benefits, such as reno-protection. However, there is no clear evidence for the superiority of RAS inhibitors to other classes of antihypertensives for clinically important outcomes in this population. We conducted a meta-analysis to assess whether RAS inhibitors are better than other classes of antihypertensives for reducing mortality, and cardiovascular and renal events in hypertensive patients with diabetes. From June to December 2017, we searched Medline, Cochrane Library, and the database of the Japan Medical Abstracts Society (ICHUSHI) for relevant published randomized controlled trials that directly compared the effects of RAS inhibitors to other classes of antihypertensives as first-line treatments for reducing adverse outcomes among hypertensive patients with diabetes. Our predetermined outcomes included all-cause death, cardiovascular death, incidence of cardiovascular disease, and renal dysfunction. We identified 16 trials, including a total of 35,052 patients. No significant benefits for RAS inhibitors were found compared to other classes of antihypertensives for all-cause death (relative risk (RR) 0.95, 95% confidence interval (CI) 0.85-1.05, p = 0.29), cardiovascular death (RR 0.84, 95% CI 0.68-1.04, p = 0.11), incidence of cardiovascular disease (RR 0.93, 95% CI 0.84-1.03, p = 0.16), and incidence of renal dysfunction (RR 0.91, 95% CI 0.77-1.06, p = 0.22). In conclusion, RAS inhibitors are not superior to other classes of antihypertensive drugs for reducing all-cause and cardiovascular mortalities, cardiovascular events, and renal events in hypertensive patients with diabetes.

Angiotensin-converting enzyme inhibitors (ACEIs) are considered primary drugs for the secondary prevention of myocardial infarction (MI), and angiotensin receptor blockers (ARBs) are used when ACEIs cannot be tolerated. However, it is unclear whether ACEIs or ARBs are more appropriate first-line drugs in hypertensive patients with MI or heart failure (HF). The present study aimed to compare the effects of ACEIs and those of ARBs in these patients. Sixty randomized controlled trails (RCTs) that compared the effects of ACEIs and ARBs in patients with MI or HF were extracted by searching PubMed/MEDLINE, Cochrane Database, and the Medical Central Journal database according to the PRISMA guidelines. We finally selected six eligible RCTs and identified three systematic reviews and meta-analyses. The proportion of hypertensive patients ranged from 36 to 69%. Meta-analyses were performed for recurrence or new onset of MI (risk ratio 0.97 [95% confidence interval: 0.88, 1.06]), hospitalization for HF (0.98 [0.84, 1.14]), cardiovascular or total mortality (0.98 [0.91, 1.05]), cardiovascular events or stroke (1.02 [0.94, 1.11]), and adverse events (1.40 [1.11, 1.77]). There were no significant differences between ACEIs and ARBs for all outcomes, except adverse events. Study discontinuation owing to adverse events was significantly more common with ACEIs than with ARBs. Among hypertensive patients with MI or HF, it appears desirable to select the most appropriate drugs, ACEIs or ARBs, in each case by considering the function level, patient background, comorbidity presence, blood pressure target, drug price and other such factors comprehensively in addition to considering tolerability.

The study evaluated the extent to which high normal blood pressure (HNBP), elevated BP, and Stage 1 hypertension predict 10-year incidence of cardiovascular disease (CVD). A population-based, prospective cohort study was conducted among 3042 randomly selected Greek adults, aged 18-89 years. Following 10-years follow-up (2002-2012), incidence of non-fatal and fatal CVD (ICD-10) was achieved in 2020 participants. The analytic sample (n = 1403) excluded hypertensive patients. At baseline, the prevalence rate of HNBP, elevated BP, and Stage 1 hypertension was 44.6% (n = 626), 29.0% (n = 408), and 15.5% (n = 218), respectively. During follow-up, the 10-year combined (fatal or non-fatal) CVD incidence rates in HNBP, elevated BP, and Stage 1 hypertensive individuals were 15.6% (n = 98), 12.0% (n = 49), and 22.5% (n = 49), respectively, as compared to 6.3% (n = 49) in normotensives (all p's < 0.0001). As compared to normotensives (and following the adjustment for known demographic, lifestyle and clinical confounding factors), HNBP participants had a 1.5-fold (Adjusted Hazard Ratio, Adj. HR: 1.49; 95% CI: 1.00-2.20) increased risk of 10-year CVD events. Similarly, Stage 1 hypertensive participants had an approximately twofold (Adj. HR: 1.90; 95% CI: 1.16-3.08) increased risk for 10-year CVD, particularly among males (Adj. HR: 2.03; 95% CI: 1.08-3.83). However, individuals with elevated BP did not exhibit a differential risk for developing 10-year CVD events (Adj. HR: 1.28; 95% CI: 0.82-2.02). Therefore, since HNBP and Stage 1 hypertension individuals exhibit a notable increased risk of 10-year fatal and non-fatal CVD, the implementation of targeted primary and secondary prevention interventions may deter both CVD and related adverse health outcomes.

Elevated visit-to-visit blood pressure variability (BPV), independent of mean BP, has been associated with cardiovascular events. However, its impact after ST-elevation myocardial infarction (STEMI) has not been established. This study aimed to investigate the prognostic impact of BPV on patients after STEMI. We analyzed the data and clinical outcomes of STEMI survivors who underwent successful primary coronary intervention from 2003 to 2009. BP was measured at discharge and at 1, 3, 6, 12, 24, and 36 months, and we calculated BPV as the intra-individual standard deviations (SDs) of systolic BP (SBP) across these measurements. We classified the patients as high and low-BPV group, and evaluated the outcomes: occurrence of major adverse cardiovascular events (MACEs), death, recurrent myocardial infarction, and target vessel revascularization within 60 months. We enrolled 343 patients, and mean follow-up duration was 68 ± 34 months (median: 76 months). Mean and median SBP SDs were 13.2 and 12.3 mmHg, and patients were divided into one of the two groups based on the median (high-BPV group = SD ≥ 12.3 mmHg; low-BPV group = SD < 12.3 mmHg). The MACE-free survival in the high-BPV group was significantly worse than that in low-BPV group (log-rank p = 0.035). For the high-BPV group, the risk of a MACE significantly increased by 57% (95% confidence interval: 1.03-2.39; p = 0.038). Visit-to-visit systolic BPV was associated with increased rates of adverse clinical outcomes in patients after STEMI. Careful assessment of BP and attempts to reduce BPV might be also important in STEMI survivors.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are drugs commonly used for the treatment of hypertension. However, studies on their comparative efficacy have not been extensively investigated. The current systematic review and network meta-analysis studied the comparative efficacy of the two antihypertensive treatment categories in reducing blood pressure, mortality, and morbidity in essential hypertension patients. A literature search was carried out in Medline and Cochrane Central Register of Controlled Trials for placebo- and active-controlled, double-blind randomized clinical trials, which had reported blood pressure effects, mortality, and/or morbidity. Blood pressure results were found in 30 studies with 7370 participants and 8 studies with 25,158 participants with mortality/morbidity results included in the analysis. The two drug classes had similar effectiveness in lowering systolic (weighted mean difference (WMD): 0.59, 95% CI: -0.21 to 1.38) and diastolic blood pressure (WMD: 0.62, 95% CI: -0.06 to 1.30), all-cause mortality (risk ratio (RR)): 0.96, 95% CI 0.80 to 1.14), cardiovascular mortality (RR: 0.87, 95% CI 0.67 to 1.14), fatal and non-fatal myocardial infarction (RR: 1.02, 95% CI 0.75 to 1.37) and stroke (RR: 1.13, 95% CI 0.87 to 1.46). Angiotensin-converting enzyme inhibitors were more helpful in the prevention and/or the hospitalization for heart failure than angiotensin receptor blockers (RR: 0.71, 95% CI 0.54 to 0.93). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were similarly effective in decreasing blood pressure, mortality, and morbidity in essential hypertension. Angiotensin-converting enzyme inhibitors were more protective in the advancement and/or hospitalization of the hypertensive patient for heart failure than angiotensin receptor blockers.

Blood pressure (BP) management posed great challenge in hemodialysis (HD) population. We conducted a dose-response meta-analysis to investigate the quantitative features and the potential threshold effect of the associations between peridialysis BP levels and all-cause mortality risk in HD population. We searched all of the prospective cohort studies (published before 18 March 2017) on the associations between peridialysis BP levels and all-cause mortality risk. A total of 229,688 prevalent HD patients from 8 studies were included. Significant non-linear associations were noted between peridialytic BP levels and all-cause mortality risk. Significant increased risk of death was found in four peridialysis BP ranges, that is, low levels of predialysis SBP (<135 mmHg, 140 mmHg as the reference), two extremes of predialysis DBP (<55 and >95 mmHg, 90 mmHg as the reference), high levels of postdialysis SBP (>180 mmHg, 130 mmHg as the reference), and low levels of postdialysis DBP (<75 mmHg, 80 mmHg as the reference). Threshold effect was determined in the associations between peridialysis BP and all-cause mortality risk, and potential BP thresholds were identified (149 mmHg for predialysis SBP, 79 mmHg for predialysis DBP, 147 mmHg for postdialysis SBP and 76 mmHg for postdialysis DBP). In conclusion, the proposed peridialysis BP ranges and the threshold values could help clinicians identify high risk HD patients. The interpretation of the peridialysis BP mortality associations should be based on the features of HD population (especially the cardiovascular conditions, volume status and the dialysis vintage).

The 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline lowered the threshold defining hypertension and treatment target from 140/90 mmHg to 130/80 mmHg. We compared the 2017 ACC/AHA guideline and the Eighth Joint National Committee (JNC8) report with regard to the current status of hypertension using the Korean National Health and Nutrition Examination Survey. The association between blood pressure (BP) control and long-term major cardiovascular outcomes (MACEs) was analyzed using the Korea National Health Insurance Service cohort. In the cross-sectional study with 15,784 adults, the prevalence of hypertension was expected to be 49.2 ± 0.6% based on the definition suggested by the 2017 ACC/AHA guideline versus 30.4 ± 0.6% based on the JNC8 report. In a longitudinal analysis with 373,800 hypertensive adults for the median follow-up periods of 11.0 years, the adults meeting the target goal BP goal of 2017 ACC/AHA guideline were associated with 21% reduced risk of MACEs compared with adults, not meeting 2017 ACC/AHA BP goal but meeting JNC8 target goal. In conclusion, substantial increase of prevalence of hypertension is expected by the 2017 ACC/AHA guideline. This study also suggests endorsing the aggressive approach would lead to an improvement in cardiovascular care.

First-line renin-angiotensin system (RAS) inhibitors are recommended for diabetic patients because of their potential nephron-protective properties. For hypertensive patients with type 2 diabetes mellitus, little is known about first-line RAS inhibitors vs. other first-line antihypertensive agents in terms of cardiovascular outcomes. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the comparative efficacy of first-line RAS inhibitors vs. other first-line antihypertensive drug classes in hypertensive patients with type 2 diabetes mellitus. We identified RCTs by searching the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE up to December 15, 2015. Eighteen RCTs involving 18,862 participants were included. First-line RAS inhibitors were not different from first-line diuretics for all the primary outcomes. First-line RAS inhibitors reduced major cardiovascular events (2 RCTs, relative risk [RR] 0.78, 95% confidence interval [CI] 0.66, 0.91) and heart failure (4 RCTs, RR 0.72, 95% CI 0.61, 0.83) compared to first-line calcium channel blockers. Compared to β-blockers, RAS inhibitors reduced the risk of all-cause mortality (1 RCT, RR 0.63, 95% CI 0.47, 0.84), major cardiovascular events (1 RCT, RR 0.76, 95% CI 0.62, 0.93) and heart failure (1 RCT, RR 0.60, 95% CI 0.40, 0.92). Our meta-analysis indicates that, in patients with type 2 diabetes mellitus and hypertension, first-line RAS inhibitors reduced adverse cardiovascular events to the same degree as first-line diuretics but to a greater degree than first-line calcium channel blockers and first-line beta blockers.

Moderately increased albuminuria, defined as urinary albumin excretion rate (UAER) between 30 and 300-mg/24-h is a well-known cardiovascular risk factor, especially in diabetic and hypertensive patients. This study aim to analyze the prognostic value of baseline UAER in a still understudied group, patients with resistant hypertension (RHT). This is a prospective observational study, which had enrolled 1048 outpatients with RHT, who were submitted to a clinical-laboratory assessment and ambulatory blood pressure monitoring (ABPM) during the follow-up. Primary endpoints were a composite of fatal and non-fatal cardiovascular events, all-cause mortality and cardiovascular mortality. Survival analysis by multiple Cox regression assessed the associations among endpoints, baseline UAER, glomerular filtration rate (GFR), and ABPM control. After a mean 7.5 years follow-up, 233 patients died, 120 from cardiac death; 215 cardiovascular events occurred, 90 strokes and 116 coronary diseases. UAER above 30-mg/24-h increased above 40% the risk of fatal and non-fatal cardiovascular events, and of all-cause mortality. At these UAER levels, secondary outcomes were associated to increased risk of stroke and risk of end-stage renal disease, but did not affect coronary events. Both the GFR below 60-mL/min and uncontrolled ABPM were related to nearly two-fold raised risk of fatal and non-fatal cardiovascular events, when coupled with UAER above 30-mg/24-h. In conclusion, moderately increased albuminuria predicts cardiovascular events and all-cause mortality in RHT, and its prognostic impact is enhanced in association with a GFR under 60-mL/min and uncontrolled baseline ABPM.

Calculating the estimated glomerular filtration rate (eGFR) using creatinine-based equations may underestimate cardiovascular risk. Cystatin C-based eGFR may be a stronger prognostic biomarker than creatinine-based eGFR when assessing cardiovascular outcomes and mortality. Our aim was to determine whether levels of serum cystatin C, as an estimator of GFR, had a higher predictive value than creatinine-based eGFR for incident cardiovascular disease among hypertensive patients. We retrospectively analyzed the records of 2016 hypertensive patients from the Hypertension Unit at Mostoles University Hospital between 2006 and 2016. We calculated the eGFR using 3 CKD-EPI equations. The outcomes we included in our study were cardiovascular death, non-cardiovascular death, stroke, incident heart failure, and myocardial infarction. We used the Cox regression hazard model to estimate the hazard ratio. Our analysis found that, in terms of cardiovascular morbidity and mortality, both cystatin C-based eGFR (HR 2.88, 95% CI 1.86-4.47, P<0.0001) showed a higher prognostic value than creatinine-based eGFR (HR 2.83, 95% CI 1.73-4.63, P<0.0001). In terms of all-cause mortality, cystatin C-based eGFR (HR 4.24, 95% CI 2.38-7.53, P<0.0001) showed a higher prognostic value than creatinine-based eGFR (HR 2.77, 95% CI 1.43-5.36, P<0.0001). Our findings suggest that both cystatin C-based eGFRs may be stronger predictors of all-cause mortality and cardiovascular events in our hypertensive cohort when compared to creatinine-based eGFR, and may improve the risk assessment in certain populations.

The purpose of this study was to evaluate the effect of combinations of blood pressure and glucose tolerance status on cardiovascular and all-cause mortality. A total of 7619 participants aged ⩾30 years old were stratified to nine categories as follows: (1) normotension (NTN) and normal glucose tolerance (NGT) (reference group), (2) NTN and pre-diabetes mellitus (pre-DM), (3) NTN and DM, (4) pre-hypertension (pre-HTN) and NGT, (5) pre-HTN and pre-DM, (6) pre-HTN and DM, (7) HTN and NGT, (8) HTN and pre-DM and (9) HTN and DM. Cox proportional hazards were applied to calculate the multivariate hazard ratios (HRs) of different groups for outcomes. For all-cause mortality outcomes, prevalent cardiovascular disease (CVD) was also adjusted. In a median follow-up of 11.3 years, 696 CVD and 412 all-cause mortality events occurred. Among the population free from CVD at baseline (n=7249), presence of HTN was associated with increased risk of CVD, regardless of glucose tolerance status with HRs of 1.97 (95% confidence interval (CI), 1.49-2.61), 2.25 (1.68-3.02) and 3.16 (2.28-4.37) for phenotypes of HTN and NGT, HTN and pre-DM and HTN and DM for CVD, respectively; corresponding HRs for all-cause mortality were 1.65 (95% CI, 1.15-2.37), 1.69 (1.15-2.49) and 2.73 (1.80-4.14), respectively. Phenotypes of NTN and pre-DM (1.48; 1.03-2.14) and NTN and DM (2.04; 1.06-3.92) were also associated with CVD and all-cause mortality, respectively. HTN was significantly associated with CVD/mortality events, regardless of glucose tolerance status. Blood pressure <120/80 mm Hg among pre-diabetic/diabetic population, not on antihypertensive medications, was generally associated with worse outcomes.

To evaluate the joint effect of hypertension (HTN) and diabetes (DM) on coronary heart disease (CHD), and stroke event, all-cause, and cardiovascular disease (CVD) mortality in Middle Eastern older adults, 2747 people (1436 women) aged ≥ 50 years, free of CVD at baseline, were categorized into four groups (HTN-/DM-, HTN+/DM-, HTN-/DM+, HTN+/DM+). Multivariate Cox proportional hazard models were run for different outcomes. To compare the impact of HTN versus DM, HTN+/DM- was considered as reference. In a median of 13.9 years, incidence rate of CHD, and stroke event, all-cause and CVD mortality in total population were 19.0, 4.7, 13.5, and 6.4 per 1000 person-years, respectively. The multivariate sex-adjusted hazard ratios (HRs) of HTN-/DM+ for CHD, stroke, all-cause mortality and CVD mortality were 1.19 (confidence interval (CI): 0.9-1.57), 1.07 (CI: 0.63-1.82), 1.62 (CI: 1.2-2.18), and 1.28 (CI: 0.83-1.97); the corresponding HRs for HTN+/DM+ were 1.96 (CI: 1.57-2.46), 1.66 (CI: 1.1-2.52), 2.32 (CI: 1.8-2.98), and 2.6 (CI: 1.85-3.65) respectively. The associations between HTN/DM status with stroke incidence and all-cause mortality were stronger among men than in women (P for interaction <0.05). Compared to HTN+/DM-, HTN-/DM+ increases all-cause mortality by 62%, however, they are not considerably different regarding CHD, stroke incidence and CVD mortality.

The added value of blood pressure (BP) trajectories for predicting cardiovascular disease (CVD) is currently unknown. We investigated the association of systolic BP (SBP) trajectories with CVD and all-cause mortality and compared these associations with those of average SBP, taking antihypertensive medication into account. Data from 762 participants of the Rancho Bernardo Study were used. SBP from five examinations (maximum) from 1984 to 2002 was used; mortality data were obtained from 2002 to 2013. SBP trajectories were derived using group-based trajectory modelling. Cox proportional hazards analysis was used to investigate associations of trajectories and average SBP with CVD and all-cause mortality, adjusted for age, sex, cholesterol, smoking, diabetes and antihypertensive medication. Mean baseline age was 65.7 years, and 67% were women. Four trajectories were identified, in which mean SBP increased by 5-12 mm Hg during 10 years. The highest trajectories were associated with two to three times greater CVD mortality and 1.5 times greater all-cause mortality risk, compared with the lowest trajectory. Each 20 mmHg increment in average SBP was associated with 1.4 times greater CVD mortality risk and 1.2 times all-cause mortality risk. Associations were not modified by antihypertensive medication (P-interaction>0.10). SBP trajectories were not superior to average SBP in predicting CVD and all-cause mortality. In the general middle-aged and older population of the Rancho Bernardo study, SBP trajectories provided no added value to average SBP in predicting CVD and all-cause mortality. Long-term average SBP levels and trajectories were significant predictors of CVD and all-cause mortality, irrespective of prescribed antihypertensive medication (which in the 1980s-1990s mainly were diuretics and β-blockers).

Renal dysfunction is frequently associated with left ventricular (LV) hypertrophy and diastolic dysfunction in hypertensive patients. Limited data exist on renal dysfunction and diastolic impairment among British ethnic minorities with hypertension. We studied associations between renal impairment and diastolic dysfunction in hypertensive subjects of African-Caribbean and South Asian origin. Five hundred and ten hypertensive subjects with ejection fraction ⩾55% and with no history of ischaemic heart disease/valve pathology were included from the original population of the Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES). Diastolic function and cardiac remodelling were measured by echocardiography. LV hypertrophy was common and present in 62% of patients with normal estimated glomerular filtration rate (eGFR, >90 ml min -1 per 1.73 m 2 ), 73% in those with eGFR 60-89 ml min -1 per 1.73 m 2 and 87% with eGFR <60 ml min -1 per 1.73 m 2 . On both univariate and multivariable linear regression, reduced eGFR was associated with higher LV mass index (LVMI, P=0.01 and P=0.039, respectively). On multivariable analyses, increased LVMI (but not eGFR) was an independent predictor of echocardiographic parameters of diastolic dysfunction. Higher LVMI was an independent predictor of all-cause or cardiovascular death on multivariable analyses (both P=0.002), but not eGFR. LV hypertrophy is common in minority ethnic groups with hypertension, especially in the presence of renal dysfunction. Increased LVMI rather than renal impairment per se is a major determinant of diastolic dysfunction and increased risk of cardiovascular or all-cause death among hypertensive patients without end-stage renal failure.

Unlabelled: We studied the relationships between blood pressure (BP), pulse pressure (PP) and cardiovascular (CV) death in older adults using data from 2346 participants enrolled in the Costa Rican CRELES study, mean age 76 years (s.d. 10.2), 31% qualified as wide PP. All covariates included and analyzed were collected prospectively as part of a 4-year home-based follow-up; mortality was tracked for an additional 3 years, identifying 266 CV deaths. Longitudinal data revealed little change over time in systolic BP (SBP), a decline in diastolic BP, and widening of PP. Wide PP was associated with higher risk of CV death but only among individuals receiving antihypertensive drug therapy. Individuals with both wide PP and receiving therapy had 2.6 hazard rate of CV death relative to people with normal-PP plus not taking treatment (TRT), even adjusting for SBP. Increasing PP between visits was significantly associated to higher CV death independently of TRT status. SBP and DBP were not significantly associated to CV death when the effect of PP was controlled for., Conclusion: elderly hypertensive patients with wide or increasing PP, especially if receiving TRT, are the highest CV risk group, thus must be carefully assessed, monitored and treated with caution.

Hypertensive emergency (HE) is a life-threatening condition that requires immediate blood pressure (BP) reduction. Although it has been on the decline, the incidence of HE has recently increased in a few countries. The aim of the present retrospective study was to evaluate the incidence, aetiology and 1-year mortality of HE in a large medical centre over a 20-year period (1991-2010). The electronic medical records of all patient files who were hospitalized in the Chaim Sheba Medical Center in Israel from 1991 to 2010 with a primary diagnosis (at admission or discharge) of Malignant Hypertension, Hypertensive Emergency or Accelerated Hypertension were retrieved and analysed. The study interval was divided into four periods of 5 years each. Among 306 files reviewed, only 142 patients had a true HE. Average age at presentation was 63.3±16.5 years. Men were younger than women (59±16 vs 68±16 years; P<0.001). At presentation, most patients (80.3%) had been diagnosed with essential hypertension previously and were undertreated. Average maximum mean arterial pressure (MAP) was higher in men (169±22 mm Hg) than in women (161±17 mm Hg; P=0.026). The rate of HE decreased over the course of the study, from 12.7/100 000 admissions during 1991-1995 to 6.2/100 000 admissions (2006-2010). Similarly, 1-year mortality decreased from 16.7 to 3.6%. The rate of HE has decreased and the prognosis has improved over the last two decades. Appropriate BP control of patients with essential hypertension may further decrease the risk of HE.

BMI, metabolic health status, and their interactions should be considered for estimating mortality risk; however, the data are controversial and unknown in Asians. We aimed to investigate this issue in Korean population. Total 323175 adults were followed-up for 96 (60-120) (median [5-95%]) months in a nationwide population-based cohort study. Participants were classified as "obese" (O) or "non-obese" (NO) using a BMI cut-off of 25 kg/m(2). People who developed ≥1 metabolic disease component (hypertension, diabetes, dyslipidaemia) in the index year were considered "metabolically unhealthy" (MU), while those with none were considered "metabolically healthy" (MH). The MUNO group had a significantly higher risk of all-cause (hazard ratio, 1.28 [95% CI, 1.21-1.35]) and cardiovascular (1.88 [1.63-2.16]) mortality, whereas the MHO group had a lower mortality risk (all-cause: 0.81 [0.74-0.88]), cardiovascular: 0.73 [0.57-0.95]), compared to the MHNO group. A similar pattern was noted for cancer and other-cause mortality. Metabolically unhealthy status was associated with higher risk of all-cause and cardiovascular mortality regardless of BMI levels, and there was a dose-response relationship between the number of incident metabolic diseases and mortality risk. In conclusion, poor metabolic health status contributed more to mortality than high BMI did, in Korean adults.

High blood pressure has been the second most important determinant of disease burden in Iran since the 1990s. Despite well-recognized evidence on the association of high blood pressure and mortality in other countries, this relationship has not been fully investigated in the demographic setting of Iran. The current study is the first large-scale longitudinal study of this association in Iran. Briefly, 50 045 subjects between 40 and 75 years of age have been recruited and followed. Blood pressure measurements were carried out at baseline. Causes of death were reported and verified by verbal autopsy throughout the follow-up period. The outcomes of interest were all-cause deaths and deaths due to ischemic heart disease (IHD) or stroke. Cox proportional hazards regression models were used to estimate hazard ratios (HRs). A total of 46 674 subjects free from cardiovascular disease at baseline were analyzed. Absolute mortality rates increased along with increasing systolic or diastolic blood pressure above 120 and 80 mm Hg, respectively. Adjusted HRs (95% confidence intervals) for each 20 mm Hg increase in systolic blood pressure in all age groups were 1.18 (1.13-1.23) for all-cause mortality, 1.21 (1.13-1.31) for deaths due to IHD and 1.50 (1.39-1.63) for deaths due to stroke. Unadjusted and adjusted HRs were higher in younger subjects and decreased with increasing age of the participants. High blood pressure is a serious threat to the health of Iranians. The entire health-care system of Iran should be involved in a comprehensive action plan for controlling blood pressure.

Elevated pulse pressure (PP) as a difference between systolic and diastolic blood pressure is a significant risk factor of cardiovascular (CV) diseases. The goal of our study was to determine the association between PP and major adverse CV events (MACEs), and all-cause and CV mortality in the different age groups of patients with coronary artery disease (CAD) confirmed by angiography. To the PROGNOSIS study, finally there were included 891 subjects with CAD. An analysis of the receiver operating characteristic was used for predicting PP dipping among the age groups of patients. A COX proportional hazards model was used to examine the association between PP and PP dipping and risk of MACE, revascularization, CV and total mortality after adjusting for sex, diabetes, smoking and low-density lipoprotein cholesterol. The median follow-up period was 8.3 years (interquartile range: 5.3-9.0 years). There were 245 (27%) all-cause deaths including 114 (13%) CV deaths during the follow-up period. MACE occurred in 442 (50%) subjects, but coronary artery interventions (percutaneous coronary intervention or coronary artery bypass grafting) were performed in 578 subjects (65%). A Cox proportional regression analysis confirmed the relationship between PP dipping as well as PP dipping thresholds points and risk of MACE and total mortality only in the group of the oldest subjects. In contrast to younger CAD patients, PP dipping is related to MACE, CV and total mortality in very elderly CAD subjects. Nocturnal PP values tend to be higher than diurnal PP values in the oldest CAD individuals. In conclusion, in contrast to younger CAD patients, PP dipping is related to MACE, CV and total mortality in very elderly CAD subjects. Nocturnal PP values tend to be higher than diurnal PP values in the oldest CAD individuals.

This study analyzed the relationship between blood pressure and all-cause mortality according to objectively measured walking speed in a Mediterranean population-based sample of older persons. We used data from the longitudinal 'Peñagrande' Cohort Study, initiated in 2008 in a sex- and age-stratified random sample of 1250 people aged ⩾65 years living in Madrid (Spain). A total of 814 individuals participated in the first study wave. The average of two standardized blood pressure readings was used. Walking speed was measured over a 3-m walk and classified as faster (⩾0.8 m s(-1)) or slower. A total of 314 individuals were slower walkers, 475 were faster walkers and 25 did not complete the walk test. Cox proportional hazards models stratified by walking speed were used to assess the association between blood pressure and all-cause death. Non-linear relationship between BP and mortality was explored by a restricted cubic spline analysis. There were 171 deaths from study entry through 31 March 2013. Systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mmHg were associated with higher mortality than blood pressure values above 140 and 90 mm Hg, respectively, but this association reached statistical significance only for systolic blood pressure and only in the slower walkers. In conclusion, systolic blood pressure levels <140 mm Hg were found associated with higher risk of total mortality among slower walkers in an old Spaniard population cohort.