Machine learning to predict myocardial injury and death after non-cardiac surgery.

Myocardial injury due to ischaemia within 30 days of non-cardiac surgery is prognostically relevant. We aimed to determine the discrimination, calibration, accuracy, sensitivity and specificity of single-layer and multiple-layer neural networks for myocardial injury and death within 30 postoperative days. We analysed data from 24,589 participants in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation study. Validation was performed on a randomly selected subset of the study population. Discrimination for myocardial injury by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.70 (0.69-0.72) vs. 0.71 (0.70-0.73) with variables available before surgical referral, p < 0.001; 0.73 (0.72-0.75) vs. 0.75 (0.74-0.76) with additional variables available on admission, but before surgery, p < 0.001; and 0.76 (0.75-0.77) vs. 0.77 (0.76-0.78) with the addition of subsequent variables, p < 0.001. Discrimination for death by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.71 (0.66-0.76) vs. 0.74 (0.71-0.77) with variables available before surgical referral, p = 0.04; 0.78 (0.73-0.82) vs. 0.83 (0.79-0.86) with additional variables available on admission but before surgery, p = 0.01; and 0.87 (0.83-0.89) vs. 0.87 (0.85-0.90) with the addition of subsequent variables, p = 0.52. The accuracy of the multiple-layer model for myocardial injury and death with all variables was 70% and 89%, respectively.

Content and delivery preferences for information to support the management of high blood pressure.

Blood pressure(BP) management interventions have been shown to be more effective when accompanied by appropriate patient education. As high BP remains poorly controlled, there may be gaps in patient knowledge and education. Therefore, this study aimed to identify specific content and delivery preferences for information to support BP management among Australian adults from the general public. Given that BP management is predominantly undertaken by general practitioners(GPs), information preferences to support BP management were also ascertained from a small sample of Australian GPs. An online survey of adults was conducted to identify areas of concern for BP management to inform content preferences and preferred format for information delivery. A separate online survey was also delivered to GPs to determine preferred information sources to support BP management. Participants were recruited via social media. General public participants (n = 465) were mostly female (68%), >60 years (57%) and 49% were taking BP-lowering medications. The management of BP without medications, and role of lifestyle in BP management were of concern among 30% and 26% of adults respectively. Most adults (73%) preferred to access BP management information from their GP. 57% of GPs (total n = 23) preferred information for supporting BP management to be delivered via one-page summaries. This study identified that Australian adults would prefer more information about the management of BP without medications and via lifestyle delivered by their GP. This could be achieved by providing GPs with one-page summaries on relevant topics to support patient education and ultimately improve BP management.

[Features of antihypertensive therapy and real-world prescription of selective imidazoline receptor agonists in Russia vs other countries: STRAIGHT study data analysis].

Analysis of routine clinical practice of hypertensive patient management represents one of the important tools in the search for further ways to minimize hypertension-associated cardiovascular and renal adverse outcomes. AIM: To compare the strategies for hypertension management and features of clinical use of I1-imidazoline receptor (I1-IR) agonists in the Russian Federation and other countries where the STRAIGHT (Selective imidazoline receptor agonists Treatment Recommendation and Action In Global management of HyperTension) study was conducted. MATERIALS AND METHODS: It was a cross-sectional online study involving physicians of various specializations. The study was conducted from January 18 to July 1, 2019, in seven countries with a high rate of I1-IR agonist prescription, including Russia. RESULTS: A total of 125 (4.5%) responders filled out the survey in the Russian Federation, which was somewhat lower than in other countries (6.8%). The participants were mostly general practitioners (54.0%) and cardiologists (42.0%), while in other countries greater diversity was seen. Most Russian physicians (83.0%) seemed to rely on national clinical guidelines in their routine practice, while in other countries the US guidelines were more popular (66.0%). The majority of responders stated that they took into account the traditional risk factors of hypertension when initiating the therapy; every second responder noted if sleep apnea was present. Awareness of I1-IR agonists, their prescription rate and their preference were higher in Russia. The main reported benefits of I1-IR agonists were their efficacy, including in resistant hypertension, and their metabolic effects (in Russia). Most participants preferred I1-IR agonists as third-line therapy (65.0% in Russia vs 60.0% in other countries) and in combination with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blockers (ARB) (55.0% in Russia vs 54.0% in other countries). Compared to responders from other countries, Russian physicians prescribe I1-IR agonists as first-line (15.0% vs 5.0%) and second-line (48.0% vs 21.0%) therapy more often. CONCLUSION: Russian physicians were the most aware of I1-IR agonists and tended to prescribe drugs of this class for hypertension management more often, and I1-IR agonist combination with ACEi was preferable compared to physician responders from other countries. Antihypertensive efficacy and metabolic effects were reported as the major benefits of I1-IR agonist therapy.

Soluble vascular endothelial growth factor receptor-1 is reduced in patients with resistant hypertension after renal denervation.

Renal denervation (RDN) has been shown in several studies to reduce blood pressure (BP) in patients with resistant hypertension (RH). Data on potential biomarkers associated with BP changes remain scarce. We evaluated whether soluble vascular endothelial growth factor receptor (sVEGFR-1) is affected by the procedure. A total of 57 patients with RH participated in this study. BP and heart rate were recorded at baseline and at 3 months follow-up, at which time blood samples were collected to determine the levels of sVEGFR-1, VEGF-A, VEGF-C, nitric oxide (NO), soluble vascular adhesion molecule 1 and soluble intracellular adhesion molecule 1. None of the biomarkers had a predictive value that could identify responders vs non-responders to RDN. However, sVEGFR-1 concentration was dramatically reduced after RDN (5913±385 vs 280±57 pg ml-1, P<0.001). At the same time VEGF-A levels were significantly increased (10.0±3.0 vs 55.5±7.9 pg ml-1, P<0.001), without significant changes in VEGF-C. NO levels were significantly increased after RDN in the whole group (82.6±6.2 vs 106.9±7.8 µM, P=0.021). Interestingly, the elevation in NO levels at 3 months was only seen in patients who demonstrated a reduction in systolic BP of ⩾10 mm Hg (78.9±8.3 vs 111.6±11.7 µM, P=0.018). We report a significant reduction in sVEGFR-1 levels after RDN procedure, which was accompanied by a significant increase in VEGF-A concentration as well as NO. Changes in plasma cytokines were not quantitatively linked to magnitude of BP reduction. An RDN-induced reduction in sVEGFR-1 plasma levels and increase in VEGF-A would raise the VEGF-A/sVEGFR-1 ratio, thereby increasing VEGF-A bioavailability to act on its full-length receptor and may contribute to the BP-lowering effect potentially via NO-mediated pathways.

A polymorphism in the norepinephrine transporter gene is associated with affective and cardiovascular disease through a microRNA mechanism.

Norepinephrine released from sympathetic nerves is removed from the neuroeffector junction via the action of the norepinephrine transporter (NET). NET impairment is evident in several clinically important conditions including major depressive disorder (MDD), panic disorder (PD), essential hypertension and the postural orthostatic tachycardia syndrome (POTS). We aimed to determine whether a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the NET gene is associated with NET impairment and to elucidate the mechanisms involved. The analyses were carried out in two cohorts of European ancestry, which included healthy controls and MDD, PD, hypertensive and POTS patients. Compared with controls, cases had significantly higher prevalence of the T allele of rs7194256 (C/T), arterial norepinephrine, depression and anxiety scores, larger left ventricular mass index, higher systolic and diastolic blood pressures, and heart rate. Bioinformatic analysis identified that the microRNA miR-19a-3p could bind preferentially to the sequence created by the presence of the T allele. This was supported by results of luciferase assays. Compared with controls, cases had significantly lower circulating miR-19a-3p, which was associated with pathways related to blood pressure and regulation of neurotransmission. In vitro norepinephrine downregulated miR-19a-3p. In conclusion, the T allele of the rs7194256 SNP in the 3'UTR of the NET gene is more prevalent in diseases where NET impairment is evident. This might be explained by the creation of a binding site for the microRNA miR-19a-3p. A defect in NET function may potentiate the sympathetic neurochemical signal, predisposing individuals with affective diseases to increased risk of cardiovascular disease development.

The role of renal denervation for the treatment of resistant hypertension.

Hypertension affects more than one-fourth of the adult population worldwide and is a major risk factor for cardiovascular and kidney disease. Currently, the majority of patients with hypertension do not reach goal blood pressure (BP) targets, and cardiovascular risk is increased further for patients with treatment-resistant hypertension, defined as office BP above goal despite pharmacological treatment with three or more antihypertensive medications at optimal doses including a diuretic. Although missed diagnosis of secondary forms of hypertension, physician inertia and non-adherence with prescribed medication are important contributors to the phenomenon of resistant hypertension that need to be addressed, there is a need for alternative therapeutic approaches. Renal sympathetic denervation is a minimally invasive endovascular procedure that disrupts renal efferent and afferent neural connections, both of which are important regulators of BP control. Limited data from recent clinical trials indicate that this approach is safe and effectively lowers BP in patients with treatment-resistant hypertension. Accumulating data is emerging to suggest that renal sympathetic denervation may also have utility beyond treatment-resistant hypertension. This review aims to briefly summarize the existing evidence for the use of renal denervation (RDN) in patients with treatment-resistant hypertension and to explore the potential utility of RDN in other pathological states associated with sympathetic dysfunction.

Chronic distress and acute vascular stress responses associated with ambulatory blood pressure in low-testosterone African men: the SABPA Study.

It is known that low testosterone (T) and high cortisol levels are associated with hypertension as well as with chronic stress, linking stress with elevated blood pressure (BP). However, the association between acute stress-, chronic stress responses and BP is not clear in Africans. Therefore, we examined the association between cortisol, psychological distress and BP responses in low- and high-T male subgroups. Beat-to-beat and ambulatory blood pressure (ABPM) and electrocardiogram measures were obtained. Serum samples were collected and analyzed for sex hormones and cortisol. Chronic psychological distress was verified with the General Health Questionnaire and acute stress with the cold pressor test. More chronic psychological distress was observed in both low- and high-T Africans compared with the Caucasians. The low-T Africans tended to have more ischemic events (P=0.06) and ABPM values (P⩽0.01) than any of the other groups. Both chronic distress (cortisol) and acute stress (total peripheral resistance cold pressor responses) were associated with ABPM in the low-T African group. Acute and chronic stress may contribute to increased BP in low-T African men. Their cortisol and vascular responses supported a tendency for ischemia, increasing their risk for coronary artery disease.

Defensive coping facilitates higher blood pressure and early sub-clinical structural vascular disease via alterations in heart rate variability: the SABPA study.

OBJECTIVES: Defensive coping (AC) responses in urban African males have been associated with vascular responsiveness, partly explaining autonomic nervous system dysfunction. We therefore aimed to assess whether AC responses facilitate higher blood pressure and early sub-clinical structural vascular disease via alterations in frequency- and time-domain heart rate variability (HRV) responses. METHODS: We included 355 African and Caucasian men and women without pre-existing atrial fibrillation, aged 45 ± 9 years. Significant interaction on main effects (coping × ethnicity × gender) for left carotid intima media thickness far wall (L-CIMTf) and cross sectional wall area values necessitated selection of AC responders above mean via the Coping Strategy Indicator. We collected B-mode ultrasound L-CIMTf, ambulatory BP and-HRV data. Overnight fasting blood was obtained. RESULTS: Overall, Africans and AC Africans, mostly men, revealed a poorer lifestyle profile, higher prevalence of hypertensive status, disturbed sympathovagal balance and depressed HRV temporal and geometric patterns compared to the Caucasians (P ≤ 0.05). Moderately depressed non-linear and time-domain HRV (SDNN <100 ms) was prevalent in 28% of Africans compared to 11% of Caucasians. A similar trend was shown for the AC African participants (32%) compared to Caucasians (16%). Only depressed HRV time-domain (SDNN: adj. R(2) = 0.34; ß = -0.24; p = 0.08) and vagal-impaired heart rate responses (RMSSD: adj. R(2) = 0.28; ß = -0.28; p < 0.05) were associated with higher blood pressure and early structural vascular changes in AC African men. CONCLUSION: Defensive coping facilitated autonomic nervous system dysfunction, which was associated with higher blood pressure and sub-clinical structural vascular disease in an African male cohort.

Higher heart rate increases risk of diabetes among men: The Australian Diabetes Obesity and Lifestyle (AusDiab) Study.

AIMS: A very limited number of prospective studies have reported conflicting data on the relation between heart rate and diabetes risk. Our aim therefore was to determine in a large, national, population-based cohort if heart rate predicts the development of diabetes. METHODS: The Australian Diabetes Obesity and Lifestyle study followed up 6537 people over 5 years. Baseline measurements included questionnaires, anthropometrics and blood and urine collection. Heart rate was recorded in beats per min (Dinamap). An oral glucose tolerance test was performed at baseline and follow-up, and diabetes was defined using World Health Organization criteria. RESULTS: A total of 5817 participants were eligible for analysis, 221 of whom developed diabetes. Compared with participants with a heart rate < 60 b min(-1), those with a heart rate ≥ 80 b min(-1) were more likely to develop diabetes (odds ratio 1.89, 95% CI 1.07-3.35) over 5 years, independent of traditional risk factors. This relationship was highly significant, particularly in non-obese men (odds ratio 5.61, 95% CI 1.75-17.98), but not in their obese counterparts or in women. CONCLUSIONS: Resting heart rate is associated with an increased risk of diabetes over a 5-year period, particularly among non-obese men. This suggests that sympathetic overactivity may be a contributing factor to the development of diabetes, and that resting heart rate may be useful in predicting risk of Type 2 diabetes in non-obese men.

Defensive active coping facilitates chronic hyperglycaemia and endothelial dysfunction in African men: the SABPA study.

BACKGROUND: Dissociation between behavioural defensive active coping (AC) control albeit physiological "loss of control" responses was associated with silent ischaemia and structural wall abnormalities in African men. Whether it applies to structural alterations and endothelial dysfunction is uncertain. We therefore aimed to determine AC ethnic-gender specific receiver operating characteristic (ROC) carotid intima media far wall (CIMTf) cut points best associated with 24-h BP, -silent ischaemia and glycated haemoglobin (HbA1c). METHODS: Participants included African and Caucasians (N=317) without pre-existing stroke or atrial fibrillation, aged 45 ± 9 years. The Coping Strategy Indicator was used to measure AC. Ultrasound CIMTf, ambulatory BP, silent ischaemia and fasting blood samples were obtained. RESULTS: Between 69 and 77% of AC African men showed above normal diastolic BP and HbA1c levels compared to 44-48% of AC Caucasian men. In AC African women, 41-60% showed above normal BP, silent ischaemia and HbA1c levels compared to 17-44% of their Caucasian counterparts. ROC curve analyses, detecting optimal CIMTf cut points, ranged between 0.57 and 0.65 mm (BP) and 0.71 and 0.74 mm (silent ischaemia) in AC ethnic-gender groups. Only HbA1C (>5.7%), with a sensitivity/specificity 47%/74%, after controlling for confounders, predicted structural alterations at an optimal cut point of 0.69 mm in AC African men (OR 4.5; 95% CI 2.93-18.73). CONCLUSION: Novel findings of behavioural resilience were apparent in the AC African female despite a high prevalence of risk markers. In AC males, chronic hyperglycaemia facilitated endothelial dysfunction, i.e. a physiological "loss of control" and susceptibility to stroke risk.

Rosuvastatin improves pulse wave reflection by restoring endothelial function.

One of the major indicators of intact endothelial function is basal nitric oxide (NO) activity. Further, it seems to be likely that statin therapy exerts beneficial effects on vascular function, at least in part via an improvement of NO bioavailability. In the present double-blind crossover study 29 hypercholesterolemic patients were randomly assigned to receive rosuvastatin and placebo for 42days. Pulse wave analysis was assessed after 30min of rest (baseline) and after infusion of N(G)-monomethyl-l-arginine (l-NMMA) at the end of 42days treatment period. The magnitude of the increase in central augmentation index (cAIx) in response to inhibition of NO synthase (NOS) by l-NMMA is indicative of basal NO activity. CAIx was significantly lower (18.3±10 versus 21.9±12%, p=0.027) with rosuvastatin compared to placebo. There was no increment of cAIx in response to l-NMMA in placebo group. In contrast, cAIx increased significantly in response to l-NMMA (20.5±11 versus 25.7±10mm Hg, p=0.001) in rosuvastatin group. The percentage of increase of cAIx tended to be more pronounced after treatment with rosuvastatin compared to placebo (53.7±92 versus 14.1±36%, p=0.087). Pulse pressure amplification (PPA) improved (1.31±0.2 versus 1.26±0.2%, p=0.016) after rosuvastatin compared to placebo. Regression analyses revealed that both LDL-cholesterol and CRP-levels are independent determinants of basal NO activity improvement, which itself is an independent determinant of vascular function, expressed by an improvement of pulse wave reflection and PPA. In this placebo controlled study, treatment with rosuvastatin improved vascular and endothelial function. Determinants for improved NO production in patients with hypercholesterolemia were the achieved levels of LDL-cholesterol and CRP. Overall, in patients without CV disease, rosuvastatin exerted beneficially effect on vascular dysfunction, one of the earliest manifestation of atherosclerosis.

The effects of dietary weight loss with or without exercise training on liver enzymes in obese metabolic syndrome subjects.

AIM: Insulin resistance and visceral adiposity are predisposing factors for fatty liver disease. The main objectives of this study were (i) to compare the effects of caloric restriction (CR) alone or together with moderate-intensity aerobic exercise training (CR+EX) on liver enzymes, a surrogate marker of liver injury, in obese metabolic syndrome (MetS) subjects and (ii) to identify anthropometric, metabolic, cardiovascular and dietary predictors of changes in liver enzymes. METHODS: Sedentary men and women (n = 63), aged 55 ± 6 (s.d.) years with body mass index 32.7 ± 4.1 kg/m(2) and confirmed MetS, were randomized to 12-week CR, CR+EX or no treatment (Control). RESULTS: Weight loss averaged 7.6% in the CR and 9.1% in the CR+EX group (time effect, p < 0.001; group effect, p = 0.11); insulin sensitivity improved by 49 and 45%, respectively (both p < 0.001). Fitness (maximal oxygen consumption) increased by 19% in the CR+EX group only (p < 0.001). Alanine aminotransferase (ALT) levels decreased by 20% in the CR and 24% in the CR+EX group (time effect, both p < 0.001; group effect, p = 0.68); corresponding values for γ-glutamyltransferase (GGT) were -28 and -33%, respectively (time effect, both p < 0.001; group effect, p = 0.28). Reduction in abdominal fat mass (measured by DXA from L1 to L4) independently predicted ΔALT (r = 0.42, p = 0.005) and ΔGGT (r = 0.55, p < 0.001), whereas change in dietary saturated fat intake was independently associated with ΔALT (r = 0.35, p = 0.03). CONCLUSIONS: Reductions in central adiposity and saturated fat intake are key drivers of improvement in liver enzymes during lifestyle interventions. Exercise training did not confer significant incremental benefits in this study.

Mediators of target organ damage in hypertension: focus on obesity associated factors and inflammation.

Arterial hypertension represents a major cardiovascular epidemic in the developed and developing world. Projections out to 2025 suggest that up to 50% of the adult populations of Western countries will meet standard guideline definitions of hypertension and thus require therapeutic intervention both non-pharmacological or pharmacological. Hyper-tension is also a component of many other major comorbidities contributing to cardiovascular disease burden. These include obesity, the metabolic syndrome, hyperlipidaemia, diabetes, and chronic kidney disease (CKD). Downstream consequences initially presenting as target organ damage of various degrees include coronary artery disease, cerebrovascular disease, nephropathy and chronic heart failure. Although elevated blood pressure per se is undoubtedly the major factor contributing to hypertensive target organ damage there is clear evidence that other mediators are also crucially involved in the transition from a healthy to a diseased state of target organs in the clinical setting of elevated blood pressure. This has obvious consequences for a multifactorial approach aimed not only at achieving target blood pressure levels but also at preventing the development or the progression of target organ damage in order to optimally reduce the overall cardiovascular risk for patients. The epidemic we are currently facing in regards to obesity is closely associated with the expected increase in the prevalence of hypertension. A closer look into the role of obesity and associated factors for the rise in blood pressure and their role in target organ damage is therefore inevitable. This review will thus focus on the clinically important aspects of target organ damage associated with hypertension, particularly obesity related hypertension, and the evidence for the involvement of neurohormonal activation and inflammatory pathways.