scholarly journals New-Onset Diabetes, Endothelial Dysfunction, and Cardiovascular Outcomes in Hypertensive Patients: An Illness-Event Model Analysis

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 721
Author(s):  
Raffaele Maio ◽  
Edoardo Suraci ◽  
Benedetto Caroleo ◽  
Cristina Politi ◽  
Simona Gigliotti ◽  
...  

Background. Insulin resistance and endothelial dysfunction are common findings in hypertensives, both predisposing to a higher risk of diabetes and cardiovascular events. We designed this study to evaluate the role of endothelial dysfunction in three pathogenetic pathways: (1) from baseline to cardiovascular events, (2) from baseline to diabetes, and (3) from new-onset diabetes to cardiovascular events. Methods. We enrolled 653 Caucasian never-treated hypertensives. Endothelial dysfunction was investigated by strain-gauge plethysmography; incident diabetes and cardiovascular events were evaluated by an illness-event model analysis. Results. During the follow-up (median 113 months), we documented 191 new cardiovascular events and 92 new cases of diabetes. In a multiple Cox regression analysis, acetylcholine-stimulated forearm blood flow [100% decrease, hazard ratio: 2.42 (95% confidence interval = 1.72–3.40)] and serum high-sensitivity C-reactive protein [hazard ratio: 1.30 (95% confidence interval = 1.21–1.40)] had an independent association with cardiovascular outcomes. The incidence rate of cardiovascular outcomes in diabetes-developer patients was higher than in the diabetes-free ones (34.9 vs. 2.5 events per 100 persons-year). In an illness-event model, a 100% decrease in forearm blood flow was associated with a 55.5% hazard ratio increase (hazard ratio: 1.56, 95% confidence interval: 1.33–1.82) of transition 1 (from baseline status to cardiovascular events) and to an almost doubled increase (hazard ratio: 2.54, 95% CI: 2.00–3.25) of the risk of transition 2 (from baseline status to diabetes). No such effects were found in transition 3 (from diabetes to cardiovascular events). Conclusions. Endothelial dysfunction plays a primary role in the pathways leading to diabetes and cardiovascular events in hypertensives. When diabetes is overt, endothelial dysfunction has no predictive value for subsequent cardiovascular events.

Author(s):  
Qin Wang ◽  
Yu Wang ◽  
Jinwei Wang ◽  
Luxia Zhang ◽  
Ming-Hui Zhao ◽  
...  

Background and objectivesNocturnal hypertension is associated with adverse outcomes in patients with CKD. However, the individual association of entities of nocturnal hypertension according to achievement of systolic and/or diastolic BP goals with kidney failure and cardiovascular outcomes of CKD is not clear.Design, setting, participants, & measurementsOur study analyzed data from participants in the Chinese Cohort Study of Chronic Kidney Disease. Nocturnal hypertension was categorized into three entities: isolated nocturnal diastolic hypertension with diastolic BP ≥70 mm Hg and systolic BP <120 mm Hg, isolated nocturnal systolic hypertension with systolic BP ≥120 mm Hg and diastolic BP <70 mm Hg, and nocturnal systolic-diastolic hypertension with both systolic BP ≥120 mm Hg and diastolic BP ≥70 mm Hg. Associations of nocturnal hypertension entities with kidney failure and cardiovascular outcomes were evaluated by Cox regression.ResultsIn total, 2024 patients with CKD stages 1–4 were included in our analysis (mean age, 49±14 years; 57% men; eGFR=51±29 ml/min per 1.73 m2; proteinuria: 0.9 [0.4–2.1] g/d). Among them, 1484 (73%) patients had nocturnal hypertension, with the proportions of 26%, 8%, and 66% for isolated nocturnal diastolic hypertension, isolated nocturnal systolic hypertension, and nocturnal systolic-diastolic hypertension, respectively. Three hundred twenty kidney events and 148 cardiovascular events were recorded during median follow-up intervals of 4.8 and 5.0 years for kidney and cardiovascular events, respectively. After adjustment, isolated nocturnal systolic hypertension was associated with a higher risk for cardiovascular events (hazard ratio, 3.17; 95% confidence interval, 1.61 to 6.23). Nocturnal systolic-diastolic hypertension showed a higher risk for both kidney failure (hazard ratio, 1.71; 95% confidence interval, 1.17 to 2.49) and cardiovascular outcomes (hazard ratio, 2.19; 95% confidence interval, 1.24 to 3.86). No association was observed between isolated nocturnal diastolic hypertension with either kidney failure or cardiovascular events.ConclusionsNocturnal systolic hypertension, either alone or in combination with diastolic hypertension, is associated with higher risks for adverse outcomes in patients with CKD.


2019 ◽  
Vol 14 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Francesca Mallamaci ◽  
Giovanni Tripepi ◽  
Graziella D’Arrigo ◽  
Silvio Borrelli ◽  
Carlo Garofalo ◽  
...  

Background and objectivesShort-term BP variability (derived from 24-hour ambulatory BP monitoring) and long-term BP variability (from clinic visit to clinic visit) are directly related to risk for cardiovascular events, but these relationships have been scarcely investigated in patients with CKD, and their prognostic value in this population is unknown.Design, setting, participants, & measurementsIn a cohort of 402 patients with CKD, we assessed associations of short- and long-term systolic BP variability with a composite end point of death or cardiovascular event. Variability was defined as the standard deviation of observed BP measurements. We further tested the prognostic value of these parameters for risk discrimination and reclassification.ResultsMean ± SD short-term systolic BP variability was 12.6±3.3 mm Hg, and mean ± SD long-term systolic BP variability was 12.7±5.1 mm Hg. For short-term BP variability, 125 participants experienced the composite end point over a median follow-up of 4.8 years (interquartile range, 2.3–8.6 years). For long-term BP variability, 110 participants experienced the composite end point over a median follow-up of 3.2 years (interquartile range, 1.0–7.5 years). In adjusted analyses, long-term BP variability was significantly associated with the composite end point (hazard ratio, 1.24; 95% confidence interval, 1.01 to 1.51 per 5-mm Hg higher SD of office systolic BP), but short-term systolic BP variability was not (hazard ratio, 0.92; 95% confidence interval, 0.68 to 1.25 per 5-mm Hg higher SD of 24-hour ambulatory systolic BP). Neither estimate of BP variability improved risk discrimination or reclassification compared with a simple risk prediction model.ConclusionsIn patients with CKD, long-term but not short-term systolic BP variability is related to the risk of death and cardiovascular events. However, BP variability has a limited role for prediction in CKD.


2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
A Aljizeeri ◽  
M Alali Alfaris ◽  
D Ahmed ◽  
J Farea ◽  
A Elneama ◽  
...  

Abstract Funding Acknowledgements None Introduction Endothelial dysfunction (ED) manifested as abnormality of coronary microvasculature is associated with poor prognosis in patients presenting with chest pain. ED can be noninvasively evaluated by assessment of coronary flow reserve with positron emission tomography (PET). Studies directly comparing ED in men and women are limited. The aim of this study is to compare gender differences in ED as measured by CFR on PET myocardial perfusion imaging. Methods All the consecutive patients referred to PET-MPI between May 2011 and June 2018 were reviewed. Patient without known CAD who had normal perfusion were included in the analysis. Patient with abnormal electrocardiogram, significant transient ischemic dilatation, low left ventricular ejection fraction and high calcium score (&gt;1000 AU) and renal failure were excluded. CFR is calculated as the ratio of stress/rest myocardial blood flow. CFR &lt; 2 was considered as abnormal indicating the presence of ED. Results 1711 patients were included in the analysis (mean age 60.2 ± 10 year, 68% females). Females were older and had higher BMI and diabetes (DM). Both resting and peak myocardial blood flow (MBF) was higher in females (1.16 vs 1.02 (p &lt; 0.0001)) and 3.26 vs 2.9 (p &lt; 0.001)0 respectively.  Around 68% of males had abnormal CFR (&lt;2) compared to 63% of females (p = 0.05). After adjusting for the confounders, female gender was associated with higher peak MBF (Hazard ratio 0.29, 95% CI 0.19 –0.40, p &lt; 0.001) and lower chance of having ED (Hazard ratio -0.15, 95% CI -0.29 - -0.005, p = 0.049) Conclusions Endothelial dysfunction as measured noninvasively by CFR on PET is prevalent among both sexes. Higher level of peak MBF in females may call for a different cut-off for abnormal CFR in women. Outcome studies are required to evaluate the clinical utility and prognostic value of such a cut-off.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Sueta ◽  
T Nishihara ◽  
E Yamamoto ◽  
K Tsujita

Abstract Background The H2FPEF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). Purpose We investigated the value of the H2FPEF score in predicting subsequent cardiovascular events in HFpEF patients. Methods This study was a retrospective, single-center, observational study. We calculated the H2FPEF scores for 404 consecutive HFpEF patients. Subjects were subdivided into low- (0–3), intermediate- (4–6), and high-score (7–9) groups and followed for 50-months. The primary and secondary endpoints were composite cardiovascular/ cerebrovascular events (cardiovascular death, non-fatal myocardial infarction, unstable angina pectoris, hospitalization for HF decompensation and non-fatal stroke) occurrence and HF-related events (hospitalization for HF decompensation) occurrence at 50-months, respectively. Results Kaplan–Meier analyses demonstrated a significantly higher incidence of cardiovascular/cerebrovascular events in proportion to a higher H2FPEF score (log-rank test, P=0.005). The HF-related event rate was higher in proportion to the H2FPEF score (log-rank test, P<0.001). Multivariate Cox hazard analyses identified the H2FPEF score (per 1 point) as an independent predictor of cardiovascular and HF-related events (Table, hazard ratio, 1.179; 95% confidence interval, 1.066–1.305; P=0.001 and hazard ratio, 1.288; 95% confidence interval, 1.134–1.463; P=0.001, respectively). Receiver operating characteristic analysis showed that the H2FPEF significantly predicted cardiovascular events (Figure A, AUC 0.626, 95% CI 0.557–0.693; P<0.001) and HF-related events (Figure B, AUC 0.680, 95% CI 0.600–0.759; P<0.001). The cutoff H2FPEF score was 5.5 for the identification of cardiovascular and HF-related events. Conclusion The H2FPEF score is a potentially useful marker for the prediction of cardiovascular and HF-related events in HFpEF patients.


2009 ◽  
Vol 94 (1) ◽  
pp. 109-114 ◽  
Author(s):  
Kai-Hang Yiu ◽  
Man-Hong Jim ◽  
Chung-Wah Siu ◽  
Chi-Ho Lee ◽  
Michele Yuen ◽  
...  

Abstract Background: Amiodarone-induced thyrotoxicosis (AIT) is a clinical condition that is notoriously difficult to manage; the relative risk of adverse cardiovascular events in these patients compared with euthyroid patients is largely unknown. Objective: We compared the clinical characteristics and major adverse cardiovascular events (MACE) in AIT and euthyroid patients. Method: Patients at a tertiary referral center who had been prescribed amiodarone for at least 3 months were retrospectively analyzed. Baseline clinical characteristics, laboratory parameters, and outcome events were evaluated. MACE was defined as cardiovascular mortality, myocardial infarction, stroke and heart failure, or ventricular arrhythmias that required hospitalization. Results: A total of 354 patients (61.8 ± 14.1 yr; 64.7% male) with a mean follow-up of 48.6 ± 26.7 months were studied. AIT, euthyroid status, and amiodarone-induced hypothyroidism were identified in 57 (16.1%), 224 (63.3%), and 73 (20.6%) patients, respectively. No differences in baseline clinical characteristics were observed between AIT and euthyroid patients. Nonetheless AIT patients demonstrated a higher MACE rate (31.6 vs. 10.7%, P &lt; 0.01), mostly driven by a higher rate of ventricular arrhythmias that required admission (7.0 vs. 1.3%, P = 0.03). Cox-regression multivariate analysis revealed that AIT (hazard ratio 2.68; confidence interval 1.53–4.68; P &lt; 0.01) and left ventricular ejection fraction less than 45% (hazard ratio 2.52; confidence interval 1.43–4.42; P &lt; 0.01) were independent predictors of MACE. Conclusion: In patients prescribed long-term amiodarone therapy, occurrence of AIT is associated with a 2.7-fold increased risk of MACE. Regular and close biochemical surveillance is thus advisable to identify and treat this high-risk group of patients.


2021 ◽  
Vol 25 (71) ◽  
pp. 1-174
Author(s):  
Jonathan Bedford ◽  
Laura Drikite ◽  
Mark Corbett ◽  
James Doidge ◽  
Paloma Ferrando-Vivas ◽  
...  

Background New-onset atrial fibrillation occurs in around 10% of adults treated in an intensive care unit. New-onset atrial fibrillation may lead to cardiovascular instability and thromboembolism, and has been independently associated with increased length of hospital stay and mortality. The long-term consequences are unclear. Current practice guidance is based on patients outside the intensive care unit; however, new-onset atrial fibrillation that develops while in an intensive care unit differs in its causes and the risks and clinical effectiveness of treatments. The lack of evidence on new-onset atrial fibrillation treatment or long-term outcomes in intensive care units means that practice varies. Identifying optimal treatment strategies and defining long-term outcomes are critical to improving care. Objectives In patients treated in an intensive care unit, the objectives were to (1) evaluate existing evidence for the clinical effectiveness and safety of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, (2) compare the use and clinical effectiveness of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, and (3) determine outcomes associated with new-onset atrial fibrillation. Methods We undertook a scoping review that included studies of interventions for treatment or prevention of new-onset atrial fibrillation involving adults in general intensive care units. To investigate the long-term outcomes associated with new-onset atrial fibrillation, we carried out a retrospective cohort study using English national intensive care audit data linked to national hospital episode and outcome data. To analyse the clinical effectiveness of different new-onset atrial fibrillation treatments, we undertook a retrospective cohort study of two large intensive care unit databases in the USA and the UK. Results Existing evidence was generally of low quality, with limited data suggesting that beta-blockers might be more effective than amiodarone for converting new-onset atrial fibrillation to sinus rhythm and for reducing mortality. Using linked audit data, we showed that patients developing new-onset atrial fibrillation have more comorbidities than those who do not. After controlling for these differences, patients with new-onset atrial fibrillation had substantially higher mortality in hospital and during the first 90 days after discharge (adjusted odds ratio 2.32, 95% confidence interval 2.16 to 2.48; adjusted hazard ratio 1.46, 95% confidence interval 1.26 to 1.70, respectively), and higher rates of subsequent hospitalisation with atrial fibrillation, stroke and heart failure (adjusted cause-specific hazard ratio 5.86, 95% confidence interval 5.33 to 6.44; adjusted cause-specific hazard ratio 1.47, 95% confidence interval 1.12 to 1.93; and adjusted cause-specific hazard ratio 1.28, 95% confidence interval 1.14 to 1.44, respectively), than patients who did not have new-onset atrial fibrillation. From intensive care unit data, we found that new-onset atrial fibrillation occurred in 952 out of 8367 (11.4%) UK and 1065 out of 18,559 (5.7%) US intensive care unit patients in our study. The median time to onset of new-onset atrial fibrillation in patients who received treatment was 40 hours, with a median duration of 14.4 hours. The clinical characteristics of patients developing new-onset atrial fibrillation were similar in both databases. New-onset atrial fibrillation was associated with significant average reductions in systolic blood pressure of 5 mmHg, despite significant increases in vasoactive medication (vasoactive-inotropic score increase of 2.3; p < 0.001). After adjustment, intravenous beta-blockers were not more effective than amiodarone in achieving rate control (adjusted hazard ratio 1.14, 95% confidence interval 0.91 to 1.44) or rhythm control (adjusted hazard ratio 0.86, 95% confidence interval 0.67 to 1.11). Digoxin therapy was associated with a lower probability of achieving rate control (adjusted hazard ratio 0.52, 95% confidence interval 0.32 to 0.86) and calcium channel blocker therapy was associated with a lower probability of achieving rhythm control (adjusted hazard ratio 0.56, 95% confidence interval 0.39 to 0.79) than amiodarone. Findings were consistent across both the combined and the individual database analyses. Conclusions Existing evidence for new-onset atrial fibrillation management in intensive care unit patients is limited. New-onset atrial fibrillation in these patients is common and is associated with significant short- and long-term complications. Beta-blockers and amiodarone appear to be similarly effective in achieving cardiovascular control, but digoxin and calcium channel blockers appear to be inferior. Future work Our findings suggest that a randomised controlled trial of amiodarone and beta-blockers for management of new-onset atrial fibrillation in critically ill patients should be undertaken. Studies should also be undertaken to provide evidence for or against anticoagulation for patients who develop new-onset atrial fibrillation in intensive care units. Finally, given that readmission with heart failure and thromboembolism increases following an episode of new-onset atrial fibrillation while in an intensive care unit, a prospective cohort study to demonstrate the incidence of atrial fibrillation and/or left ventricular dysfunction at hospital discharge and at 3 months following the development of new-onset atrial fibrillation should be undertaken. Trial registration Current Controlled Trials ISRCTN13252515. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 71. See the NIHR Journals Library website for further project information.


2003 ◽  
Vol 95 (6) ◽  
pp. 2218-2222 ◽  
Author(s):  
John Pernow ◽  
Felix Böhm ◽  
Emma Beltran ◽  
Adrian Gonon

It has been shown that nitric oxide (NO) protects from myocardial ischemia-reperfusion injury in animal models. The present study investigated whether administration of the NO substrate l-arginine protects against ischemia-reperfusion-induced endothelial dysfunction in humans. Forearm blood flow was measured with venous occlusion plethysmography in 16 healthy male subjects who were investigated on two occasions. Forearm ischemia was induced for 20 min followed by 60-min reperfusion. With the use of a crossover protocol, the subject received a 15-min intrabrachial artery infusion of l-arginine (20 mg/min) and vehicle (saline, n = 12 or d-arginine, n = 4) starting at 15 min of ischemia on two separate occasions. Compared with preischemia, endothelium-dependent increase in forearm blood flow induced by intra-arterial acetylcholine (3–30 μg/min) was significantly impaired at 15 and 30 min of reperfusion when the subjects received saline ( P < 0.001). When the subjects received l-arginine, the acetylcholine-induced increase in forearm blood flow was not significantly affected by ischemia-reperfusion. The recovery of endothelium-dependent vasodilatation at 15- and 30-min reperfusion was significantly greater after administration of l-arginine than after saline ( P < 0.05). d-Arginine did not affect the response to acetylcholine. Endothelium-independent vasodilatation to nitroprusside was not affected during reperfusion. These results demonstrate that the NO substrate l-arginine significantly attenuates ischemia-reperfusion-induced endothelial dysfunction in humans in vivo. This suggests that l-arginine may be useful as a therapeutic agent in the treatment of ischemia-reperfusion injury in humans.


2020 ◽  
Vol 21 (6) ◽  
pp. 892-899
Author(s):  
Kanyu Miyamoto ◽  
Takashi Sato ◽  
Keisuke Momohara ◽  
Sumihisa Ono ◽  
Makoto Yamaguchi ◽  
...  

Background: Although percutaneous transluminal angioplasty has been established as a first-line therapy for access failure in dialysis, there are few reports on primary patency after percutaneous transluminal angioplasty. We investigated factors associated with primary patency following the first percutaneous transluminal angioplasty performed after vascular access construction in patients with arteriovenous fistula, including blood flow volume before and after percutaneous transluminal angioplasty and previously reported factors. Methods: We used medical records at six dialysis centers to retrospectively identify and analyze prognostic factors for primary patency after percutaneous transluminal angioplasty in 159 patients with arteriovenous fistula who underwent initial percutaneous transluminal angioplasty after vascular access construction. Results: Multivariate analysis with the Cox proportional hazard model showed that primary patency after percutaneous transluminal angioplasty in patients with arteriovenous fistula was significantly associated with lesion length (hazard ratio, 1.76; 95% confidence interval, 1.01–3.07; P = 0.045), and blood flow volume after percutaneous transluminal angioplasty (hazard ratio, 0.71; 95% confidence interval, 0.60–0.84; P < 0.001). When blood flow volume after percutaneous transluminal angioplasty was classified into three categories, risks of outcome events defining the end of primary patency after percutaneous transluminal angioplasty were significantly lower for 400–630 mL/min (hazard ratio, 0.38; 95% confidence interval, 0.21–0.68; P = 0.001) and >630 mL/min (hazard ratio, 0.16; 95% confidence interval, 0.06–0.40; P < 0.001) compared with <400 mL/min. Conclusion: Our study showed that blood flow volume after percutaneous transluminal angioplasty is an important prognostic factor for primary patency after percutaneous transluminal angioplasty in patients with arteriovenous fistula.


2016 ◽  
Vol 106 (1) ◽  
pp. 21-27 ◽  
Author(s):  
S. Upala ◽  
A. Sanguankeo ◽  
V. Jaruvongvanich

Objectives: Gallstone disease shares certain risk factors with cardiovascular disease, particularly metabolic risk factors. Patients with gallstone disease may be at increased risk of cardiovascular disease. Several recent studies exploring the effect of gallstone disease on cardiovascular disease outcomes demonstrated inconsistent results. Design: We conducted a systematic review and meta-analysis of cohort, case–control, and cross-sectional studies that compared the risk of developing cardiovascular disease events in patients with gallstone disease versus non-gallstone disease controls. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the pooled hazard ratio, odd ratio, and 95% confidence interval. Results: Data were extracted from six studies involving 176,734 cases and 803,714 controls. The pooled hazard ratio of cardiovascular events in patients with gallstone disease was 1.28 (95% confidence interval: 1.23–1.33, I2 = 42%). The pooled odd ratio of cardiovascular events in patients with gallstone disease was 1.82 (95% confidence interval: 1.47–2.24, I2 = 68%). Conclusions: Our study demonstrated a statistically significant increase in the risk of cardiovascular disease among patients with gallstone disease.


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