A European Renal Association (ERA) synopsis for nephrology practice of the 2023 European Society of Hypertension (ESH) Guidelines for the Management of Arterial Hypertension.

In June 2023, the European Society of Hypertension (ESH) presented and published the new 2023 ESH Guidelines for the Management of Arterial Hypertension, a document that was endorsed by the European Renal Association (ERA). Following the evolution of evidence in recent years, several novel recommendations relevant to the management of hypertension in patients with chronic kidney disease (CKD) appeared in these Guidelines. These include recommendations for target office blood pressure (BP) <130/80 mmHg in most and against target office BP <120/70 mmHg in all patients with CKD; recommendations for use of spironolactone or chlorthalidone for patients with resistant hypertension with estimated glomerular filtration rate (eGFR) higher or lower than 30 mL/min/1.73 m2, respectively; use of a sodium-glucose cotransporter 2 inhibitor for patients with CKD and estimated eGFR ≥20 mL/min/1.73 m2; use of finerenone for patients with CKD, type 2 diabetes mellitus, albuminuria, eGFR ≥25 mL/min/1.73 m2 and serum potassium <5.0 mmol/L; and revascularization in patients with atherosclerotic renovascular disease and secondary hypertension or high-risk phenotypes if stenosis ≥70% is present. The present report is a synopsis of sections of the ESH Guidelines that are relevant to the daily clinical practice of nephrologists, prepared by experts from ESH and ERA. The sections summarized are those referring to the role of CKD in hypertension staging and cardiovascular risk stratification, the evaluation of hypertension-mediated kidney damage and the overall management of hypertension in patients with CKD.

Anthropometric Measures of Adiposity as Markers of Kidney Dysfunction: A Cross-Sectional Study.

The present study was designed to provide information on the ability of several different anthropometric markers to reflect the renal impairment associated with body weight increase and to predict the development of renal alterations linked to overweight and obesity. In 574 subjects representative of the general population of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study, with an age range between 57 and 73 years, we investigated the association between different anthropometric markers of body fat, as alternative to body mass index, and renal failure, to obtain information useful for determining their potential predictive value. Renal dysfunction was significantly associated with almost all anthropometric markers of adiposity related to body weight and body shape. After adjustment for confounders, such as age, sex, office blood pressure, serum glucose, antihypertensive drugs and smoking habit, association remained significant only for waist-to-hip ratio (WHR), lipid accumulation product (LAP) and visceral adiposity index (VAI). These 3 markers also displayed at the receiver operating curves (ROC) analysis the best ability to detect subjects with or without kidney dysfunction. The results of the present study provide evidence that WHR, LAP and VAI represent the best markers of renal dysfunction associated with visceral body fat accumulation.

Coffee consumption, clinic, 24-hour and home blood pressure. Findings from the PAMELA study.

BACKGROUND AND AIMS: Chronic coffee consuption has been reported to be associated with a modest but significant increase in blood pressure (BP), although some recent studies have shown the opposite. These data, however, largely refer to clinic BP and virtually no study evaluated cross-sectionally the association between chronic coffee consuption, out-of-office BP and BP variability. METHODS AND RESULTS: In 2045 subjects belonging to the population of the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, we analyzed cross-sectionally the association between clinic, 24-hour, home BP and BP variability and level of chronic coffee consumption. Results show that when adjusted for confounders (age, gender, body mass index, cigarette smoking, physical activity and alcohol drinking) chronic coffee consumption does not appear to have any major lowering effect on BP values, particulary when they are assessed via 24-hour ambulatory (0 Cup/day: 118.5 ± 0.7/72.8 ± 0.4 mmHg vs 3 cups/day: 120.2 ± 0.4/74.8 ± 0.3 mmHg, PNS) or home BP monitoring (0 cup/day: 124.1 ± 1.2/75.4 ± 0.7 mmHg vs 3 cups/day: 123.3 ± 0.6/76.4 ± 0.36 mmHg, PNS). However, daytime BP was significantly higher in coffee consumers (about 2 mmHg), suggesting some pressor effects of coffee which vanish during nighttime. Both BP and HR 24-hour HR variability were unaffected. CONCLUSION: Thus chronic coffee consumption does not appear to have any major lowering effect either on absolute BP values, particulary when they are assessed via 24-hour ambulatory or home BP monitoring, or on 24-hour BP variability.

Simple cardiovascular risk stratification by replacing total serum cholesterol with anthropometric measures: The MORGAM prospective cohort project.

To assess whether anthropometric measures (body mass index [BMI], waist-hip ratio [WHR], and estimated fat mass [EFM]) are independently associated with major adverse cardiovascular events (MACE), and to assess their added prognostic value compared with serum total-cholesterol. The study population comprised 109,509 individuals (53% men) from the MORGAM-Project, aged 19-97 years, without established cardiovascular disease, and not on antihypertensive treatment. While BMI was reported in all, WHR and EFM were reported in âˆ¼52,000 participants. Prognostic importance of anthropometric measurements and total-cholesterol was evaluated using adjusted Cox proportional-hazards regression, logistic regression, area under the receiver-operating-characteristic curve (AUCROC), and net reclassification improvement (NRI). The primary endpoint was MACE, a composite of stroke, myocardial infarction, or death from coronary heart disease. Age interacted significantly with anthropometric measures and total-cholesterol on MACE (P ≤ 0.003), and therefore age-stratified analyses (<50 versus ≥ 50 years) were performed. BMI, WHR, EFM, and total-cholesterol were independently associated with MACE (P ≤ 0.003) and resulted in significantly positive NRI when added to age, sex, smoking status, and systolic blood pressure. Only total-cholesterol increased discrimination ability (AUCROC difference; P < 0.001). In subjects < 50 years, the prediction model with total-cholesterol was superior to the model including BMI, but not superior to models containing WHR or EFM, while in those ≥ 50 years, the model with total-cholesterol was superior to all models containing anthropometric variables, whether assessed individually or combined. We found a potential role for replacing total-cholesterol with anthropometric measures for MACE-prediction among individuals < 50 years when laboratory measurements are unavailable, but not among those ≥ 50 years.

Characteristics of hypertension and arterial stiffness in obstructive sleep apnea: A Scandinavian experience from a prospective study of 6408 normotensive and hypertensive patients.

The impact of obstructive sleep apnea (OSA) on arterial stiffness is less studied. We aimed to investigate the prevalence and covariates of increased pulse pressure (PP), a surrogate marker of arterial stiffness, in the entire study population as well as in separate analyses in normotensive and hypertensive patients. Further, we also explored the impact of smoking on brachial BP in hypertensive patients. Between 2012 and 2019, a total of 6408 participants with suspected OSA underwent a standard out-of-center respiratory polygraphy. OSA was defined by an apnea-hypopnea index (AHI) ≥15/h regardless of symptoms. PP ≥60 mmHg was used as a surrogate marker of increased arterial stiffness. Mean age was 49.3±13.7 years, 69.4% were male, and 34.5% had OSA. The prevalence of hypertension was 70.8% in OSA and 46.7% in No-OSA (AHI < 15/h) controls (P < .0001). Hypertension was controlled (clinic BP < 140/90 mmHg) in 45.5% and uncontrolled in 54.5% (P < .001). Mean PP was 50±12 mmHg in smokers and 52±12 mmHg in non-smokers (P = .001). Increased PP was found in 24.2% of the entire study population and was higher in patients with OSA compared to No-OSA group (27.5% vs 22.4%, P < .0001). In an unadjusted logistic regression model, OSA was associated with a 1.3-fold higher risk of having increased PP (95% CI 1.16-1.48, P < .001). In a multivariable-adjusted model, higher age, male sex, and history of hypertension, but not OSA (OR 0.89; 95% CI 0.77-1.02, P = .104) were associated with increased PP. In this large study of nearly 6500 participants who were referred with suspected OSA, one-third were diagnosed with OSA and a quarter had increased arterial stiffness by elevated brachial PP. Hypertension but not OSA per se was associated with increased arterial stiffness. Hypertension was highly prevalent and poorly controlled.

Persistence of protection against SARS-CoV-2 clinical outcomes up to 9 months since vaccine completion: a retrospective observational analysis in Lombardy, Italy.

BACKGROUND: Scarce information is available on the duration of the protective effect of COVID-19 vaccination against the risk of SARS-CoV-2 infection and its severe clinical consequences. We investigated the effect of time since vaccine completion on the SARS-CoV-2 infection and its severe forms. METHODS: In this retrospective observational analysis using the vaccination campaign integrated platform of the Italian region of Lombardy, 5 351 085 individuals aged 12 years or older who received complete vaccination from Jan 17 to July 31, 2021, were followed up from 14 days after vaccine completion until Oct 20, 2021. Changes over time in outcome rates (ie, SARS-CoV-2 infection and severe illness among vaccinated individuals) were analysed with age-period-cohort models. Trends in vaccine effectiveness (ie, outcomes comparison in vaccinated and unvaccinated individuals) were also measured. FINDINGS: Overall, 14 140 infections and 2450 severe illnesses were documented, corresponding to incidence rates of 6·7 (95% CI 6·6-6·8) and 1·2 (1·1-1·2) cases per 10 000 person-months, respectively. From the first to the ninth month since vaccine completion, rates increased from 4·6 to 10·2 infections, and from 1·0 to 1·7 severe illnesses every 10 000 person-months. These figures correspond to relative reduction of vaccine effectiveness of 54·9% (95% CI 48·3-60·6) for infection and of 40·0% (16·2-57·0) for severe illness. The increasing infection rate was greater for individuals aged 60 years or older who received adenovirus-vectored vaccines (from 4·0 to 23·5 cases every 10 000 person-months). The increasing severe illness rates were similar for individuals receiving mRNA-based vaccines (from 1·1 to 1·5 every 10 000 person-months) and adenovirus-vectored vaccines (from 0·5 to 0·9 every 10 000 person-months). INTERPRETATION: Although the risk of infection after vaccination, and even more of severe illness, remains low, the gradual increase in clinical outcomes related to SARS-CoV-2 infection suggests that the booster campaign should be accelerated and that social and individual protection measures against COVID-19 spread should not be abandoned. FUNDING: None.

Nonalcoholic fatty liver disease and risk of incident hypertension: a systematic review and meta-analysis.

Several studies reported an association between nonalcoholic fatty liver disease (NAFLD) and the risk of incident hypertension. The objective of this systematic review and meta-analysis was to obtain a precise and reliable estimate of the nature and magnitude of this association. We systematically searched Ovid-MEDLINE up to March 2021 for observational studies in which NAFLD was diagnosed in adults using blood-based panels, imaging techniques or liver biopsy and with a follow-up ≥1 year. Measures of association from individual studies were meta-analyzed using random-effects models. Of the 1108 titles initially scrutinized, we included 11 cohort studies with data on 390 348 participants (52% male) and a mean follow-up of 5.7 years. In the overall analysis, NAFLD was associated with a moderately increased risk of incident hypertension (hazard ratio 1.66; 95% confidence interval (CI), 1.38-2.01; test for overall effect z = 5.266; P < 0.001). There was significant heterogeneity among the studies (P < 0.001). Sensitivity analyses showed that estimates were not affected by geographical location, duration of follow-up and adjustment for baseline blood pressure values. On the other hand, the magnitude of the association was lower in studies that adjusted for baseline adiposity compared with those that did not, explaining part of the observed heterogeneity. No significant publication bias was detected by funnel plot analysis and Egger's and Begg's tests. This large meta-analysis indicates that NAFLD is associated with a ~1.6-fold increased risk of developing hypertension. Further studies are needed to investigate the role of NAFLD severity in terms of inflammation and fibrosis on incident hypertension.

Left ventricular global longitudinal strain in secondary hypertension: A meta-analysis of echocardiographic studies.

AIM: Information on systolic dysfunction, as assessed by left ventricular (LV) mechanics in secondary hypertension is still largely limited. We performed a systematic meta- analysis of 2D/3D speckle tracking studies in order to provide an updated comprehensive information on this topic. METHODS: The PubMed, OVID-MEDLINE, and Cochrane library databases were analysed to search for articles published from the inception up to March 31st 2021. Studies were identified by using MeSH terms and crossing the following search items: "myocardial strain" "left ventricular mechanics", "speckle tracking echocardiography", "systolic dysfunction", "hypertensive heart disease", "left ventricular hypertrophy", "secondary hypertension", "primary aldosteronism", "pheochromocytoma", "Cushing disease", "renal artery stenosis". RESULTS: On the whole, 515 patients with secondary hypertension (169 pheochromocytoma, 165 primary aldosteronism, 144 renal artery stenosis and 37 Cushing's syndrome) and 601 essential hypertensive patients from 11 studies were considered. Pooled ejection fraction (EF) was similar in essential hypertensive controls and in patients with secondary hypertension (SMD 0.12±0.06, CI: 0.001/0.25, p=0.05). Of note, EF was higher in patients with pheochromocytoma than in essential hypertensives (0.50±0.11, CI: 0.27/0.73, p<0.001). In contrast, pooled GLS was impaired in patients with secondary hypertension compared to their essential hypertensive counterparts (SMD 0.83±0.26, CI: 0.32/1.30, p< 0.001). CONCLUSIONS: The present meta-analysis adds a new piece of evidence by showing that GLS performs better than EF in identifying systolic dysfunction in the setting of secondary hypertension. In particular, this is true in patients with pheochromocytoma in whom conventional EF suggests a normal or even super-normal systolic function.

Cost-effectiveness of the adherence with recommendations for clinical monitoring of patients with diabetes.

BACKGROUND AND AIMS: To validate a set of indicators for monitoring the quality of care of patients with diabetes in 'real-life' practice through its relationship with measurable clinical outcomes and healthcare costs. METHODS AND RESULTS: A population-based cohort study was carried out by including the 20,635 patients, residents in the Lombardy Region (Italy), who in the year 2012 were newly taken-in-care for diabetes. Adherence with clinical recommendations (i.e., controls for glycated haemoglobin, lipid profile, urine albumin excretion and serum creatinine) was recorded during the first year after the patient was taken-in-care, and categorized according whether he/she complied with none or almost none (0 or 1), just some (2) or all or almost all (3 or 4) the recommendations, respectively denoted as poor, intermediate and high adherence. Short- and long-term complications of diabetes, and healthcare cost incurred by the National Health Service, were assessed during follow-up. Compared with patients with poor adherence, those with intermediate and high adherence respectively showed (i) a delay in outcome occurrence of 13 days (95% CI, -2 to 27) and 23 days (9-38), and (ii) a lower healthcare cost of 54 € and 77 €. In average, a gain of 18 Euros and 15 Euros for each day free from diabetic complication by increasing adherence respectively from poor to intermediate and from poor to high were observed. CONCLUSION: Close control of patients with diabetes through regular clinical examinations must be considered the cornerstone of national guidance, national audits, and quality improvement incentive schemes.

Seasonal variation in estimated cardiovascular risk in patients with type 2 diabetes.

BACKGROUND AND AIMS: Seasonal variations in several risk factors for cardiovascular events (CVD) were described. Here, we evaluate the impact of seasonal variations in blood pressure (BP), lipid profile and glycemic control on estimated CVD risk in patients with type 2 diabetes (T2D). METHODS AND RESULTS: Retrospective monocentric study of patients with T2D who were visited at least once in the winter period and once in the summer period, less than 8 months apart, for which data related to systolic (S) BP, diastolic (D) BP, body mass index, glycosylated hemoglobin (HbA1c), total cholesterol, HDL cholesterol and smoking habit were available on both occasions. The 10-year CVD risk was calculated using the UKPDS risk engine and the ASCVD risk estimator. As many as 411 patients were included in the study. Significant within-patient differences between summer and winter were found for the absolute risk of events assessed with both calculators (Δs-w UKPDS-CHD: -1.33%, Δs-w UKPDS-Stroke: -0.84%, Δs-w ASCVD: -2.21%). The seasonal change in SBP was the main responsible for the change in risk estimated with both the UKPDS-Stroke (r2 = 0.43) and the ASCVD (r2 = 0.50) scores, while the change in total cholesterol was the main determinant of the change in risk for the UKPDS-CHD (r2 = 0.34). A significant correlation was identified between changes in temperature and changes in SBP (ρ = 0.130, p = 0.008), but not in other risk factors. CONCLUSIONS: Seasonal variations in the classic CVD risk factors influence the risk estimated using validated calculators.

History of lower-limb complications and risk of cancer death in people with type 2 diabetes.

BACKGROUND: Individuals with diabetes and lower-limb complications are at high risk for cardiovascular and all-cause mortality, but uncertainties remain in terms of cancer-related death in this population. We investigated this relationship in a large cohort of people with type 2 diabetes. METHODS: We used data from the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. The primary outcome was adjudicated cancer death; secondary outcomes were overall and site-specific incident cancers, determined according to the International Classification of Diseases Code (ICD-10). We compared outcomes in individuals with (versus without) a baseline history of lower-limb complications (peripheral artery disease (PAD) or sensory peripheral neuropathy) using Cox regression models. RESULTS: Among 11,140 participants (women 42%, mean age 66 years), lower-limb complications were reported at baseline in 4293 (38%) individuals: 2439 (22%) with PAD and 2973 (27%) with peripheral neuropathy. Cancer death occurred in 316 (2.8%) participants during a median of 5.0 (25th-75th percentile, 4.7-5.1) years of follow-up corresponding to 53,550 person-years and an incidence rate of 5.9 (95% CI 5.3-6.6) per 1000 person-years. The risk of cancer death was higher in individuals with (versus without) lower-limb complication [hazard ratio 1.53 (95% CI, 1.21-1.94), p = 0.0004], PAD [1.32 (1.02-1.70), p = 0.03] or neuropathy (1.41 (1.11-1.79), p = 0.004], adjusting for potential confounders and study allocations. PAD, but not neuropathy, was associated with excess risk of incident cancers. CONCLUSIONS: PAD and peripheral neuropathy were independently associated with increased 5-year risk of cancer death in individuals with type 2 diabetes. PAD was also associated with increased risk of incident cancers. Our findings provide new evidence on the non-cardiovascular prognostic burden of lower-limb complications in people with type 2 diabetes.

Lifestyle, psychological, socioeconomic and environmental factors and their impact on hypertension during the coronavirus disease 2019 pandemic.

SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic considerably affects health, wellbeing, social, economic and other aspects of daily life. The impact of COVID-19 on blood pressure (BP) control and hypertension remains insufficiently explored. We therefore provide a comprehensive review of the potential changes in lifestyle factors and behaviours as well as environmental changes likely to influence BP control and cardiovascular risk during the pandemic. This includes the impact on physical activity, dietary patterns, alcohol consumption and the resulting consequences, for example increases in body weight. Other risk factors for increases in BP and cardiovascular risk such as smoking, emotional/psychologic stress, changes in sleep patterns and diurnal rhythms may also exhibit significant changes in addition to novel factors such as air pollution and environmental noise. We also highlight potential preventive measures to improve BP control because hypertension is the leading preventable risk factor for worldwide health during and beyond the COVID-19 pandemic.

Left ventricular mass reduction and hypertrophy regression following renal artery revascularization: a meta-analysis.

AIM: Few echocardiographic studies have focused on regression of left ventricular hypertrophy (LVH) in patients with renal artery stenosis after revascularization, with inconsistent results. We performed a systematic meta-analysis of these studies in order to offer a comprehensive information on this topic. METHODS: The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English-language articles published from 1 January 1990 up to 31 March 2020. Studies were identified by crossing the following terms: 'renal artery stenosis', 'renovascular hypertension', 'fibromuscular dysplasia', 'renal artery stenting', 'renal artery surgery' with 'cardiac damage', 'hypertensive heart disease' 'left ventricular mass', 'left ventricular hypertrophy', 'echocardiography'. RESULTS: A total of 726 hypertensive patients with renal artery stenosis (mean age 61 years, 64% men, 98% treated, 10% with fibromuscular dysplasia) were included in 13 studies. Baseline and postintervention pooled mean LVM values were 220 ±â€Š15 and 203 ±â€Š19 g, respectively (SMD -0.24 ±â€Š0.06, CI -0.37 to -0.21, P<0.0001); corresponding values for LV mass index were 129.0 ±â€Š6 and 115 ±â€Š7 g/m, respectively (SMD -0.28 ±â€Š0.04, CI -0.36 to 0.21, P < 0.0001). Renal revascularization was associated with a 40% lower risk of LVH. This trend was accompanied by a reduction in the number of antihypertensive drugs (SMD -0.27 ±â€Š0.04, CI -0.37 to 0.17, P < 0.0001). CONCLUSION: The present meta-analysis suggests that renal artery revascularization added to antihypertensive therapy promotes a favourable effect on LV structure, as reflected by a significant decrease in absolute and indexed LV mass index as well by a lower risk of LVH. Limitations include: high prevalence of modest renal artery stenosis (≥50%); small sample of fibromuscular dysplasia; lack of randomized design of most studies.

A practical approach to switch from a multiple pill therapeutic strategy to a polypill-based strategy for cardiovascular prevention in patients with hypertension.

: Pharmacological treatment recommended by guidelines for very high-risk patients with established cardiovascular disease (CVD) includes lipid-lowering drugs, antihypertensive agents and antiplatelet therapy. Depending on the associated comorbidities, this baseline regimen has to be complemented with other drugs. Therefore, the number of pills to be taken is usually high and adherence to these multiple pill therapeutic regimens and long-term persistence on treatment is low, being the main factor for insufficient control of cardiovascular risk factors. The CNIC (Centro Nacional de Investigaciones Cardiovasculares, Ministerio de Ciencia e Innovación, España) polypill is the only polypill containing low-dose aspirin approved by the EMA and marketed in Europe, and has demonstrated to improve adherence. For this reason, guidelines recommend its use for secondary prevention of CVD, and also for primary prevention of cardiovascular events in patients with multiple cardiovascular risk factors and advanced atherosclerotic process at high risk of thrombosis and low risk of bleeding. This article pretends to simplify the steps that clinicians may follow to switch from any baseline regimen to the polypill with the use of several algorithms and tables showing the equivalent effective daily doses of different angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and statins to facilitate switching, as well as the steps to be followed depending of the initial levels of BP and LDL-cholesterol values to achieve BP and lipid control with the association to the polypill of other BP-lowering or lipid-lowering drugs whenever needed.

Sympathetic Overactivation in Patients With Essential Hypertension and Hepatic Iron Overload.

Iron overload has been recently shown to be associated with a hyperadrenergic state in genetic hemochromatosis. Whether this is also the case in essential hypertension, characterized by sympathetic activation and frequently by body iron overload, is unknown. In 17 healthy normotensive controls (age 52.3±3.2 years, mean±SE), in 21 age-matched patients with hypertension with iron overload (HT+), defined by serum ferritin levels, and in 28 hypertensives without this condition, we measured efferent postganglionic muscle sympathetic nerve traffic (microneurography), heart rate and blood pressure variability (power spectral analysis), serum ferritin, and metabolic variables. Muscle sympathetic nerve traffic was significantly (P<0.02 at least) greater in HT+ than in patients with hypertension without iron overload and normotensive subjects both when expressed as bursts incidence over time (41.8±1.4 versus 31.5±1.4 and 23.6±0.9 bursts/min) and as bursts corrected for heart rate (55.3±1.8 versus 42.3±1.2 and 31.7±1.2 bursts/100 heartbeats). In HT+, low-frequency systolic blood pressure variability was significantly reduced. In HT+, but not in the other 2 groups, muscle sympathetic nerve traffic was significantly related to serum ferritin (r=0.51, P<0.03), transferrin saturation (r=0.47, P<0.03), and hepatic iron load (r=0.76, P<0.0001, magnetic resonance imaging), as well as to homeostatic model assessment index values (r=0.46, P<0.05). These data provide the first evidence that in HT+ elevated serum ferritin is associated with a hyperadrenergic state of greater magnitude than the one seen in patients with hypertension without iron overload. They also show that the potentiation of the sympathetic activation detected in HT+ is related to elevated serum ferritin and to the associated metabolic alterations, possibly participating in the increased cardiovascular risk characterizing iron overload.

Alternative kidney filtration markers and the risk of major macrovascular and microvascular events, and all-cause mortality in individuals with type 2 diabetes in the ADVANCE trial.

BACKGROUND: Creatinine-based estimated glomerular filtration rate (eGFR) is biased in the setting of obesity and other conditions. Alternative kidney filtration markers may be useful in adults with diabetes, but few studies examined the associations with risk of clinical outcomes. METHODS: In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, we evaluated whether baseline levels and change in eGFR based on creatinine (Cr), cystatin c (Cys), ß2 -microglobulin (B2M), eGFRCr-Cys , and the average of three estimates (eGFRCr-Cys-B2M ) assessed in 7217 participants at baseline and a random sample of 640 participants at the 1-year visit are associated with clinical outcomes. We examined associations with major macrovascular and microvascular events together and separately and all-cause mortality using Cox regression models, adjusting for established risk factors. RESULTS: Over a median follow-up of 5 years, 1313 major macrovascular (n = 748) and microvascular events (n = 637), and 743 deaths occurred. Lower levels of eGFR based on all filtration markers individually and combined were associated with 1.4 to 3.0 times higher risk of major macrovascular and microvascular events (combined and separately) and all-cause mortality. Per 30% decline in eGFRCys , eGFR Cr-Cys , and eGFRCr-Cys-B2M were associated with a >2-fold higher risk of all clinical outcomes. CONCLUSIONS: In adults with type 2 diabetes, baseline levels of eGFR based on alternative filtration markers and per 30% decline in eGFRCys , eGFR Cr-Cys , and eGFRCr-Cys-B2M were associated with clinical outcomes. Measurement of alternative filtration markers, particularly B2M in adults with type 2 diabetes may be warranted.

Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in US Adults Across Blood Pressure Categories.

Nonalcoholic fatty liver disease (NAFLD) is common in patients with hypertension but controversy exists as to whether screening for this condition should be performed. Here, we evaluate the prevalence of NAFLD and advanced fibrosis in US adults across blood pressure categories and estimate the number of patients who require referral to hepatologists. In this cross-sectional analysis of 11 489 adults from the 2005 to 2016 National Health and Nutrition Examination Survey, participants were segregated as having optimal, normal, high normal, and elevated blood pressure according to the 2018 European Society of Cardiology/Hypertension guidelines. NAFLD was defined using the US fatty liver index, whereas fibrosis was assessed using the NAFLD fibrosis score, fibrosis-4, and Hepamet Fibrosis Score. NAFLD prevalence increased progressively from optimal (16.5%) to normal (34.5%), high normal (39.9%), and elevated blood pressure (50.2%, P<0.001). Patients with hypertension also showed a higher prevalence of advanced fibrosis (3%-9%, based on the specific biomarker used). When the screening flowchart from the European Association for the Study of the Liver, Diabetes, and Obesity guidelines was applied to patients with hypertension, 26.7% needed referral to hepatologists. Risk of referral was higher in Hispanic patients and those with diabetes mellitus, heart failure, and an altered urinary albumin excretion. NAFLD is highly prevalent in US adults with hypertension and a quarter of them would need to be referred to hepatologists because of a high risk of advanced fibrosis. While future studies on cost-effectiveness are needed, screening for NAFLD in these patients could be beneficial.

Does Estimated Pulse Wave Velocity Add Prognostic Information?: MORGAM Prospective Cohort Project.

The Reference Values for Arterial Stiffness Collaboration has derived an equation using age and mean blood pressure to estimated pulse wave velocity (ePWV), which predicted cardiovascular events independently of Systematic COoronary Risk Evaluation (SCORE) and Framingham Risk Score. The study aim was to investigate the independent association between ePWV and clinical outcomes in 107 599 apparently healthy subjects (53% men) aged 19 to 97 years from the MORGAM Project who were included between 1982 and 2002 in 38 cohorts from 11 countries. Using multiple Cox-regression analyses, the predictive value of ePWV was calculated adjusting for country of inclusion and either SCORE, Framingham Risk Score, or traditional cardiovascular risk factors (age, sex, smoking, systolic blood pressure, body mass index [BMI], total and high-density lipoprotein cholesterol). Cardiovascular mortality consisted of fatal stroke, fatal myocardial infarction, or coronary death, and the composite cardiovascular end point consisted of stroke, myocardial infarction, or coronary death. Model discrimination was assessed using Harrell's C-statistic. Adjusting for country and logSCORE or Framingham Risk Score, ePWV was associated with all-cause mortality (hazard ratio, 1.23 [95% CI 1.20-1.25] per m/s or 1.32 [1.29-1.34]), cardiovascular mortality (1.26 [1.21-1.32] or 1.35 [1.31-1.40]), and composite cardiovascular end point (1.19 [1.16-1.22] or 1.23 [1.20-1.25]; all P<0.001). However, after adjusting for traditional cardiovascular risk factors, ePWV was only associated with all-cause mortality (1.15 [1.08-1.22], P<0.001) and not with cardiovascular mortality (0.97 [0.91-1.03]) nor composite cardiovascular end point (1.10 [0.97-1.26]). The areas under the last 3 receiver operator characteristic curves remained unchanged when adding ePWV. Elevated ePWV was associated with subsequent mortality and cardiovascular morbidity independently of systematic coronary risk evaluation and Framingham Risk Score but not independently of traditional cardiovascular risk factors.