European Lipid Guidelines and Cardiovascular Risk Estimation: Current Status and Future Challenges.

PURPOSE OF REVIEW: Genetic, experimental, epidemiologic, and clinical data support the causal role of elevated levels of low-density lipoprotein cholesterol (LDL-C) in atherosclerosis and cardiovascular disease (CVD). The recommendations of the 2019 European guidelines are based on the concept of differential CV risk, which in turn defines the LDL-C goals that should be achieved. RECENT FINDINGS: The 2019 ESC/EAS guidelines for dyslipidaemia use the Systematic COronary Risk Evaluation (SCORE) model to assess CV risk, which provides a 10-year risk of fatal CV event. The SCORE model has recently been updated to reflect current rates of cardiovascular disease in Europe. The new SCORE2 model provides estimates of the 10-year risk of fatal and non-fatal CVD events in people aged 40-69 years, thus improving the identification of individuals at higher risk of a CVD event. However, as in the SCORE age is the main determinant of risk, young people have a relatively low estimated 10-year risk of a CV event even with high levels of one or more causal risk factors. Individuals with familial hypercholesterolaemia, who have elevated LDL-C levels from birth and have a high risk of premature CVD, are one example. The concept of cumulative LDL exposure is thus becoming increasingly important. This is also supported by Mendelian randomisation studies showing that carrying genetic variants associated with lower LDL-C levels reduces CV risk. These observations have introduced the concept of "cholesterol-years", which takes into account both LDL-C levels and time of exposure. It is crucial that future European guidelines pay more attention to this point.

Skin Autofluorescence as a Potential Adjunctive Marker for Cardiovascular Risk Assessment in Type 2 Diabetes: A Systematic Review.

Diabetes mellitus (DM), due to its long-term hyperglycemia, leads to the accumulation of advanced glycation end-products (AGEs), especially in the vessel walls. Skin autofluorescence (SAF) is a non-invasive tool that measures AGEs. DM patients have a rich dietary source in AGEs, associated with high oxidative stress and long-term inflammation. AGEs represent a cardiovascular (CV) risk factor, and they are linked with CV events. Our objective was to assess whether SAF predicts future CV events (CVE) by examining its association with other CV risk factors in patients with type 2 DM (T2DM). Additionally, we assessed the strengths and limitations of SAF as a predictive tool for CVE. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology, we conducted a systematic review with CRD42024507397 protocol, focused on AGEs, T2DM, SAF, and CV risk. We identified seven studies from 2014 to 2024 that predominantly used the AGE Reader Diagnostic Optic tool. The collective number of patients involved is 8934, with an average age of 63. So, SAF is a valuable, non-invasive marker for evaluating CV risk in T2DM patients. It stands out as a CV risk factor associated independently with CVE. SAF levels are influenced by prolonged hyperglycemia, lifestyle, aging, and other chronic diseases such as depression, and it can be used as a predictive tool for CVE.

The Pandemic of Coronary Artery Disease in the Sub-Saharan Africa: What Clinicians Need to Know.

PURPOSE OF REVIEW: Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality globally with an accelerated increase in CVD­related death in Africa and other low­middle­income countries. This review is aimed at highlighting the burden of coronary artery disease CAD, its peculiarities as well as challenges of management in sub-Saharan Africa. RECENT FINDINGS: Recent data revealed a shift from high incidence of CVDs associated with poverty and malnutrition (such as rheumatic heart disease) initially, which are now falling, to rising incidence of other non-communicable CVDs (such as hypertension, coronary artery disease (CAD), and heart failure). Africa disproportionately bears the brunt of CVD burden and has one of the highest risks of dying from non-communicable diseases (NCDs) worldwide, which is projected to supersede communicable diseases in the future. Previous studies have shown that CAD was rare among Africans. Those studies conducted in Africa in the 1940s-1960s reported that Black Africans were almost immune to developing CAD and were even thought to have specific genetic make-up protecting them from CAD. However, the continent is now experiencing a steady rise in the prevalence of CAD associated with severe disease burden, compared to other regions of the world. The changes seen have been attributed to the current epidemiological transition with increase in CVD risk factors that are poorly controlled, lack of awareness as well as the poor health facilities to tackle the menace of the disease. The Global Burden of Disease (GBD) estimates have also shown that over the past three decades the highest contribution to CVD burden in Africa is attributed to atherosclerotic diseases, with 71.4, 37.7, and 154% increases in the burden of ischemic heart disease, stroke, and peripheral artery disease respectively. There is a steady increase of CAD prevalence in Africa as a result of increase in CV risk factors. Hypertension, obesity, diabetes, dyslipidemia, and cigarette smoking are the rapidly rising risk factors for CAD on the continent. Africa also faces challenges in diagnosis and management of CAD. There is need for increased public and health personnel awareness on prevention and control of commonly identifiable risk factors, provision of prehospital emergency services, and provision of modern therapeutic facilities for treatment of CAD including reperfusion therapy. These are priority areas where efforts could be intensified in the future with potential to improve the current rate of progress of the disease on the continent.

Determinants of LV mass in athletes: the impact of sport, constitutional traits and cardiovascular risk factors.

BACKGROUND: Whether cardiovascular (CV) risk factors might impact Left Ventricular (LV) mass in athletes is unknown. METHODS: The impact of CV risk factors (Total/LDL cholesterol, triglycerides, positive family history, smoking, body fat, blood pressure), constitutional characteristics (age, sex, body mass index) and type of sport was assessed in 1111 Olympic athletes. RESULTS: Multivariate logistic regression analysis demonstrated a significant impact: BMI ≥ 30 kg/m2 (odds ratio [OR] = 2.8. 95° Confidence Interval [CI] 0.9-13.7; < 0.001; in males); age ≥ 20-year (OR = 2.1, CI 1.4-3.3; p < 0.001) in males; (OR = 2.3; CI 1.4-3.7) in females; systolic blood pressure ≥ 130 mmHg (OR = 1.1, CI 1.01-1.16; p < 0.001) in males; (OR = 1.03; CI 1.01-1.06; p < 0.03) in females; diastolic ≥ 85 mmHg (OR = 1.1, CI 1.03-1.2; p = 0.003) in males; (OR = 1.05, CI 1.02-1.08, p < 0.001) in females. No association was found for family history, smoking, body fat, LDL, total cholesterol, triglycerides. Overall, constitutional traits explain > 60% of the LV mass. Sport explains on average 14%, but large differences existed among disciplines, i.e., endurance showed the highest impact (55%, mixed: 20%, power: 17%, skill: 8%; p < 0.001). CONCLUSION: LV mass in athletes is largely governed by constitutional traits and type of sport, and independent from CV risk factors, except for systolic and diastolic blood pressure. Overall, constitutional traits explain more than 60% of LV mass. The impact of sport is largely different in relation to the discipline, and highest in endurance, moderate mixed and power and mild in skill disciplines.

The challenge of early glomerular filtration rate decline in response to antihypertensive treatment and chronic kidney disease outcomes.

Hypertension and chronic kidney disease (CKD) are closely linked pathological processes. Combating high blood pressure (BP) is an essential part of preventing CKD progression and reducing cardiovascular (CV) risk. Data from recent randomized controlled trials on patients at high CV risk showed the beneficial effects of intensive action to meet BP targets on mortality related to CV disease. The impact of meeting such targets on renal function is still unclear, however, particularly for patients with CKD. This issue has been the object of several post hoc analyses because lowering BP definitely has a nephroprotective role, but the early decline in glomerular filtration rate (GFR) associated with antihypertensive therapies and strict BP targets is still a concern in nephrology clinical practice. The present review discusses the results of studies on this topic, focusing specifically on the clinical significance of early GFR decline in response to treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, or to different BP targets, in terms of renal and CV outcomes, and how this tips the balance towards continuing or discontinuing antihypertensive therapy.

Hypertension attenuates the link of osteoprotegerin to reduced baroreflex sensitivity in type 2 diabetes mellitus patients on oral antidiabetic and antihypertensive therapy - a cross sectional study.

PURPOSE: Decreased baroreflex sensitivity (BRS) has been shown to be a marker of cardiovascular (CV) risk. In the present study, the difference in CV risk biomarkers in type 2 diabetes (T2D) patients receiving oral antidiabetic drugs (OAD) with and without hypertension has been assessed. MATERIALS AND METHODS: Ninety-two T2D patients on OAD without hypertension (control group) and eighty-eight diabetic patients with hypertension on OAD and antihypertensive drugs (test group) matched for age, gender, body mass index, serum glucose, glycated haemoglobin, and duration of the disease were recruited for the study. Their blood pressure (BP) variability including BRS, heart rate variability (HRV), insulin, lipid profile, osteoprotegerin (OPG), and tumor necrosis factor-α (TNF-α) were estimated. The association of various factors with BRS was assessed by Spearman correlation and multiple regression analysis. RESULTS: BRS was decreased (13.90 ± 5.27 vs 6.76 ± 4.58), HRV sympathetic indices [LFnu, LF-HF ratio (1.30 ± 0.49 vs 1.93 ± 0.62)], HOMA-IR, atherogenic index of plasma (AIP), OPG (223.08 ± 103.86 vs 287.60 ± 121.36) and TNF-α were increased, and parasympathetic indices [TP (1012.90 ± 316.18 vs 625.88 ± 229.84), RMSSD, SDNN, NN50, pNN50] were decreased in the test group compared to control group. In control group, parasympathetic indices, AIP, OPG, and TNF-α had a significant correlation and OPG had an independent association (ß - 0.344; p 0.004) with BRS. In test group, BP, LF-HF ratio, parasympathetic indices, AIP, OPG, and TNF-α had significant correlation, and TNF-α alone (ß - 0.297; p 0.022) had an independent contribution to decreased BRS. CONCLUSION: Despite antidiabetic and antihypertensive treatments, T2D patients with hypertension had more cardiometabolic risks in comparison to normotensive T2D patients. Inflammation could be the inciting factor for rise in BP and decrease in BRS (CV risk) in hypertensive T2D patients. Hypertension in diabetes could attenuate the link of OPG to the reduction in BRS. Reduction in BRS could be a physiological marker of CV risk in T2D patients treated with OAD.

Glucagon-Like Peptide 1 Receptor Agonists (GLP1RA) and Sodium-glucose co-transporter-2 inhibitors (SGLT2i): Making a pragmatic choice in diabetes management.

The availability of newer glucose-lowering drugs has created opportunities for comprehensive diabetes care. Two classes of drugs, GLP1RA (glucagon-like peptide 1 receptor agonists), and SGLT2i (sodium glucose cotransporter 2 inhibitors) have demonstrated their efficacy in glucose control as well as cardiovascular risk reduction. While both can be used together, there is an ongoing debate regarding their relative advantages and limitations. We present a clinical perspective to compare and control these two classes of drugs, and promote rational prescription in diabetes praxis.

Efficacy and durability of multifactorial intervention on mortality and MACEs: a randomized clinical trial in type-2 diabetic kidney disease.

BACKGROUND: Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. METHODS: Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure < 130/80 mmHg, glycated haemoglobin < 7%, LDL, HDL and total cholesterol < 100 mg/dL, > 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. RESULTS: At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4-13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30-0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29-0.93, P = 0.027). CONCLUSION: MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925.

Association of Arterial Stiffness With Chronic Kidney Disease Progression and Mortality.

Chronic kidney disease (CKD) is a major public health concern. Despite many potentially life-threatening conditions that can accompany kidney disease, cardiovascular disease (CVD) remains the leading cause of death in these patients. Adjusted-for-age mortality from CVD in patients with end-stage renal disease is 10-30 times higher than in the general population. A decrease in renal function accelerates the development of cardiac pathology. Simultaneous exposure of CVD and CKD plays an important role in the relationship between arterial stiffness (AS) and estimated glomerular filtration rate. But there is a controversy as to whether the AS causes deterioration in kidney function, if renal dysfunction leads to AS, or the relationship is reciprocal. Hence, several studies that recruited high-risk populations reached a conclusion that comorbidities might lead to both AS and decline in kidney function over time. A number of studies have shown that several markers of AS, such as pulse pressure, central and peripheral pressure are associated with the development of CKD. This review takes into account the theoretical background, current status, and future potential of the techniques that measure AS within context of CKD assessment and management.

Apolipoprotein B and non-high-density lipoprotein cholesterol reveal a high atherogenicity in individuals with type 2 diabetes and controlled low-density lipoprotein-cholesterol.

BACKGROUND: Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c) levels, although the cardiovascular disease (CVD) risk could be better reflected by other lipid parameters. This study aimed at comparing a comprehensive lipid profile between patients with type 2 diabetes mellitus (T2DM) with LDL-c concentration within and above target. METHODS: A comprehensive lipid profile was characterized in 96 T2DM patients. The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. RESULTS: In this population, only 28.1 and 16.7% of patients had mean LDL-c levels within target, as defined by the 2016 and 2019 guidelines, respectively. Applying the 2016 guidelines criteria, in patients with LDL-c within target, 22, 25 and 44% presented non-high-density lipoprotein cholesterol (non-HDL-c), Apolipoprotein B (ApoB) and oxidized LDL-c levels above the recommended range, respectively, whereas according to the 2019 guidelines criteria, 50, 39 and 44% of the patients with LDL-c within target had elevated high-density lipoprotein cholesterol (HDL-c), ApoB and oxidized LDL-c levels, respectively. LDL-c was strongly correlated with non-HDL-c (r = 0.850), ApoB (r = 0.656) and oxidized LDL-c (r = 0.508). Similarly, there was a strong correlation between non-HDL-c with both ApoB (r = 0.808) and oxidized LDL-c (r = 0.588). CONCLUSIONS: These findings emphasize the limitations of only considering LDL-c concentration for cardiovascular (CV) risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM patients. These data suggest that non-HDL-c, ApoB and oxidized LDL-c levels could be considered as an important part of these patients' evaluation allowing for a more accurate estimation of CV risk and hopefully better management of these high-risk patients.

Notes on the new “Recommendations for the treatment of dyslipidemia. Influencing of lipids to reduce cardiovascular risk”.

New guidelines on dyslipidemia (DLP) related problems appear earlier than planned. Primarily in view of the results of science and large clinical studies, but also with regard to the advent of biological therapy (PCSK9-i) in many Euro-pean countries. Also, the “conventional” hypolipidemic therapy is generified and therefore cheaper, more af-fordable. The recommendations are based, as the preceding ones, on the principle of estimating the overall cardiovascular risk. The innovated SCORE tables are used for this, but more emphasis is placed on non-invasive dia-gnostics using imaging methods, be it carotid ultrasound or, in particular, non-contrast CT coronarography. Perhaps the most significant outcome is the reduction of LDL-cholesterol (LDL-C) target values to 1.4 mmol/l and a 50% reduction of baseline LDL-C in patients belonging to the highest risk groups, and in secondary prevention. Moreover, in the case of “extreme” risk the goal is to reduce LDL-C below 1 mmol/l. Essential to DLP therapy is statin treatment. Especially in patients with acute coronary syndrome and those in the highest risk categories, the maximum tolerated doses of statin should be used, if necessary in combination with ezetimibe. Where this maximum “routine” treatment is insufficient to achieve the target values, PCSK9-i therapy is indicated. However the recommendations do not by any means omit non-pharmacological therapy, quite the opposite, it is always emphasized as the first step of DLP therapy. Worthy of notice is the introduction of the term “atherosclerotic cardiovascular disease” - ASCVD, which replaces the older and less accurate CVD.

Fixed-dose combination of rosuvastatin and ezetimibe.

Atherosclerotic cardiovascular diseases (ASCVD) play a significant role in morbidity and mortality not only in developed but also increasingly in developing countries. The only causal risk factor (RF) of ASKVO is LDL-cholesterol. The basic pillar of pharmacotherapy of dyslipidaemias are statins, which should be titrated to the maximum (tolerated) dose and then combined with ezetimibe if the LDL-cholesterol targets for the specific categories of CV risk are not reached. Combination therapy is known to be far more effective than increasing the statin dose. Fixed combinations of statins with ezetimibe can be advantageously used to improve adherence.

Comparative Effectiveness of Medical Therapy, Percutaneous Revascularization, and Surgical Coronary Revascularization in Cardiovascular Risk Subgroups of Patients With CKD: A Retrospective Cohort Study of Medicare Beneficiaries.

RATIONALE & OBJECTIVE: Prior studies suggesting that medical therapy is inferior to percutaneous (percutaneous coronary intervention [PCI]) or surgical (coronary artery bypass grafting [CABG]) coronary revascularization in chronic kidney disease (CKD) have not adequately considered medication optimization or baseline cardiovascular risk and have infrequently evaluated progression to kidney failure. We compared, separately, the risks for kidney failure and death after treatment with PCI, CABG, or optimized medical therapy for coronary disease among patients with CKD stratified by cardiovascular disease risk. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 34,385 individuals with CKD identified from a national 20% Medicare sample who underwent angiography or diagnostic stress testing without (low risk) or with (medium risk) prior cardiovascular disease or who presented with acute coronary syndrome (high risk). EXPOSURES: PCI, CABG, or optimized medical therapy (defined by the addition of cardiovascular medications in the absence of coronary revascularization). OUTCOMES: Death, kidney failure, composite outcome of death or kidney failure. ANALYTICAL APPROACH: Adjusted relative rates of death, kidney failure, and the composite of death or kidney failure estimated from Cox proportional hazards models. RESULTS: Among low-risk patients, 960 underwent PCI, 391 underwent CABG, and 6,426 received medical therapy alone; among medium-risk patients, 1,812 underwent PCI, 512 underwent CABG, and 9,984 received medical therapy alone; and among high-risk patients, 4,608 underwent PCI, 1,330 underwent CABG, and 8,362 received medical therapy alone. Among low- and medium-risk patients, neither CABG (HRs of 1.22 [95% CI, 0.96-1.53] and 1.08 [95% CI, 0.91-1.29] for low- and medium-risk patients, respectively) nor PCI (HRs of 1.14 [95% CI, 0.98-1.33] and 1.02 [95% CI, 0.93-1.12], respectively) were associated with reduced mortality compared with medical therapy, but in low-risk patients, CABG was associated with a higher rate of the composite, death or kidney failure (HR, 1.25; 95% CI, 1.02-1.53). In high-risk patients, CABG and PCI were associated with lower mortality (HRs of 0.57 [95% CI, 0.51-0.63] and 0.70 [95% CI, 0.66-0.74], respectively). Also, in high-risk patients, CABG was associated with a higher rate of kidney failure (HR, 1.40; 95% CI, 1.16-1.69). LIMITATIONS: Possible residual confounding; lack of data for coronary angiography or left ventricular ejection fraction; possible differences in decreased kidney function severity between therapy groups. CONCLUSIONS: Outcomes associated with cardiovascular therapies among patients with CKD differed by baseline cardiovascular risk. Coronary revascularization was not associated with improved survival in low-risk patients, but was associated with improved survival in high-risk patients despite a greater observed rate of kidney failure. These findings may inform clinical decision making in the care of patients with both CKD and cardiovascular disease.

Effectiveness of Pharmacist Interventions on Cardiovascular Risk in Patients With CKD: A Subgroup Analysis of the Randomized Controlled RxEACH Trial.

BACKGROUND: Affecting a substantial proportion of adults, chronic kidney disease (CKD) is considered a major risk factor for cardiovascular (CV) events. It has been reported that patients with CKD are underserved when it comes to CV risk reduction efforts. STUDY DESIGN: Prespecified subgroup analysis of a randomized controlled trial. SETTING & PARTICIPANTS: Adults with CKD and at least 1 uncontrolled CV risk factor were enrolled from 56 pharmacies across Alberta, Canada. INTERVENTION: Patient, laboratory, and individualized CV risk assessments; treatment recommendations; prescription adaptation(s) and/or initiation as necessary; and regular monthly follow-up for 3 months. OUTCOMES: The primary outcome was change in estimated CV risk from baseline to 3 months after randomization. Secondary outcomes were change between baseline and 3 months after randomization in individual CV risk factors (ie, low-density lipoprotein cholesterol, blood pressure, and hemoglobin A1c), risk for developing end-stage renal disease, and medication use and dosage; tobacco cessation 3 months after randomization for those who used tobacco at baseline; and the impact of rural versus urban residence on the difference in change in estimated CV risk. MEASUREMENTS: CV risk was estimated using the Framingham, UK Prospective Diabetes Study, and international risk assessment equations depending on the patients' comorbid conditions. RESULTS: 290 of the 723 participants enrolled in RxEACH had CKD. After adjusting for baseline values, the difference in change in CV risk was 20% (P<0.001). Changes of 0.2mmol/L in low-density lipoprotein cholesterol concentration (P=0.004), 10.5mmHg in systolic blood pressure (P<0.001), 0.7% in hemoglobin A1c concentration (P<0.001), and 19.6% in smoking cessation (P=0.04) were observed when comparing the intervention and control groups. There was a larger reduction in CV risk in patients living in rural locations versus those living in urban areas. LIMITATIONS: The 3-month follow-up period can be considered relatively short. It is possible that larger reduction in CV risk could have been observed with a longer follow up period. CONCLUSIONS: This subgroup analysis demonstrated that a community pharmacy-based intervention program reduced CV risk and improved control of individual CV risk factors. This represents a promising approach to identifying and managing patients with CKD that could have important public health implications.

Is increased uric acid a risk factor or a defensive response? The Campania Salute Network.

BACKGROUND AND AIMS: Circulating uric acid (UA) is positively associated with body mass index (BMI), blood glucose, blood pressure (BP), markers of inflammation, and altered lipid profile. UA has also anti-oxidative properties which might be beneficial for cardiovascular (CV) system. It is still debated whether or not UA is independently associated with increased CV morbidity and/or mortality. METHODS AND RESULTS: We studied prognostic impact of UA in 8833 hypertensive adults (mean age 53 ± 12 yrs, 3857 women) from the Campania Salute Network, without prevalent CV disease and more than stage 3 CKD. We calculated standardized UA Z-score, adjusted for age, sex, glomerular filtration rate, and BMI. Low and high UA and UA Z-score quartiles were compared to the 2 middle quartiles assumed to be "normal". Prevalence of obesity and diabetes was higher in low and high than in normal UA Z-score group (all p < 0.001). Systolic BP, left ventricular mass, carotid intima thickness were significantly higher and ejection fraction was reduced in the presence of high UA Z-score (all p < 0.001). Over 33-months average follow-up, incident major CV end-points (MACE) were not significantly different among low, normal and high UA or UA Z-score. In the latter analysis, however, incident MACE tended to be more frequent in the low than the high UA Z-score. Despite the results of multivariable analyses, the effect of less aggressive therapy in low UA Z-score cannot be excluded with certainty. CONCLUSION: In treated hypertensive patients, high levels of UA normalized for major biological determinants do not independently predict CV outcome. CLINICALTRIALS. GOV IDENTIFIER: NCT02211365.

Evaluation of cardiovascular risk in stages of gout by a complex multimodal ultrasonography.

The aim of our work was to assess ultrasound features of cardiovascular (CV) risk in stages of gout. Cross-sectional complex multimodal ultrasound study of 169 age-matched patients, with similar distribution of arterial hypertension, diabetes mellitus, obesity and chronic renal failure, was divided into four groups: 41 with asymptomatic hyperuricemia, 52 gout without tophi, 42 gouty tophi and 34 controls with osteoarthritis. Parameters independently associated with CV risk were measured: renal resistive index (RRI), left ventricular mass index (LVMi), mitral annulus early diastolic velocity (e'), intima-media thickness (IMT) and common carotid artery resistive index (CCARI). Multivariate analyses were performed to evaluate the impact of gout stages and CV risk factors on ultrasound alterations. Gouty tophi increased the risk of having IMT >0.90 mm with an OR 11.51 (95 % CI 2.32-57.21, p = 0.003), gout without tophi raised the risk with an OR 6.25 (95 % CI 1.37-28.44, p = 0.018), while asymptomatic hyperuricemia had no effect on IMT. The category of CCARI >0.70 was influenced by tophi with an OR 11.18 (95 % CI 2.61-47.83, p = 0.001) and by arterial hypertension with an OR 3.22 (95 % CI 1.11-9.36, p = 0.032). Neither asymptomatic hyperuricemia nor gout without tophi modified the development of abnormally high CCARI. Gout stages had no impact on LVMi, e' and RRI. Tophi are related to worsened ultrasonographic parameters evaluating target organs in gout, relative to earlier stages of the disease. They create a strong risk of carotid arteries' changes even beyond arterial hypertension.

Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women's Health Initiative.

BACKGROUND: Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women's Health Initiative. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n=8,921), African American (n=7,436), or Hispanic (n=3,054) were used to calculate estimated glomerular filtration rates (eGFRs). PREDICTORS: Categories of eGFR (exposure); race/ethnicity (effect modifier). OUTCOMES: The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death. MEASUREMENTS: We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity. RESULTS: During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories. LIMITATIONS: Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics. CONCLUSIONS: In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.

Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial.

BACKGROUND: Asymptomatic hyperuricemia increases renal and cardiovascular (CV) risk. We previously conducted a 2-year, single-blind, randomized, controlled trial of allopurinol treatment that showed improved estimated glomerular filtration rate and reduced CV risk. STUDY DESIGN: Post hoc analysis of a long-term follow-up after completion of the 2-year trial. SETTING & PARTICIPANTS: 113 participants (57 in the allopurinol group and 56 in the control group) initially followed up for 2 years and 107 participants followed up to 5 additional years. INTERVENTION: Continuation of allopurinol treatment, 100mg/d, or standard treatment. OUTCOME: Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or ≥50% decrease in estimated estimated glomerular filtration rate) and CV events (defined as myocardial infarction, coronary revascularization or angina pectoris, congestive heart failure, cerebrovascular disease, and peripheral vascular disease). RESULTS: During initial follow-up, there were 2 renal and 7 CV events in the allopurinol group compared with 6 renal and 15 CV events in the control group. In the long-term follow-up period, 12 of 56 participants taking allopurinol stopped treatment and 10 of 51 control participants received allopurinol. During long-term follow-up, an additional 7 and 9 participants in the allopurinol group experienced a renal or CV event, respectively, and an additional 18 and 8 participants in the control group experienced a renal or CV event, respectively. Thus, during the initial and long-term follow-up (median, 84 months), 9 patients in the allopurinol group had a renal event compared with 24 patients in the control group (HR, 0.32; 95% CI, 0.15-0.69; P=0.004; adjusted for age, sex, baseline kidney function, uric acid level, and renin-angiotensin-aldosterone system blockers). Overall, 16 patients treated with allopurinol experienced CV events compared with 23 in the control group (HR, 0.43; 95% CI, 0.21-0.88; P=0.02; adjusted for age, sex, and baseline kidney function). LIMITATIONS: Small sample size, single center, not double blind, post hoc follow-up and analysis. CONCLUSIONS: Long-term treatment with allopurinol may slow the rate of progression of kidney disease and reduce CV risk.

Adverse cardiovascular events associated with triptans and ergotamines for treatment of migraine: systematic review of observational studies.

BACKGROUND: Apart from the underlying cardiovascular (CV) risk associated with migraine, both triptans and ergotamines can induce vasoconstriction and potentially increase the risk of serious ischemic events. Because of the low frequency of such events in eligible patients, randomized controlled trials are not exhaustive to assess the drug-related CV risk. Observational studies are, therefore, an essential source of information to clarify this matter of concern. AIM: The aim of this study was to systematically review the available published observational studies investigating the risk of serious CV events in triptan or ergotamine users, as compared to unexposed migraineur controls. METHODS: We systematically searched MEDLINE and EMBASE electronic databases for cohort or case-control studies up to December 1, 2013. Studies retrieved from CDSR, DARE and HTA databases of the Cochrane Library were used for snowballing. Studies investigating the risk of any CV outcome in patients with a migraine diagnosis and exposed to triptans or ergotamines were considered for inclusion. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were computed using a random-effects model for studies and outcomes judged eligible for quantitative data synthesis. RESULTS: From a total of 3370 citations retrieved, after duplicate removal and screening, only four studies met the inclusion criteria (three nested case-control analyses and one retrospective cohort study). These studies investigated the risk of different CV outcomes associated with either the recency or the intensity of exposure to the studied drugs. As for the intensity of use, the pooled OR of serious ischemic events was 2.28 (95% CI 1.18-4.41; I (2 )= 0%) for ergotamine use (two studies), whereas for triptans (three studies) it was 0.86 (95% CI 0.52-1.43; I (2 )= 24.5%). Recent use of ergotamines was not significantly associated with any CV outcome (only one available study). Two studies investigated the risk of stroke related to recent triptan use: the first study reported an OR of 0.90 (0.64-1.26), and the second one suggested an increased risk of 2.51 (1.10-5.71). In this case, because of the high degree of heterogeneity, results were not pooled. CONCLUSIONS: To date, few comparative observational studies have investigated the CV safety of migraine-specific drugs in clinical practice. Evidence gathered here suggests that intense consumption of ergotamines may be associated with an increased risk of serious ischemic complications. As for triptans, available studies do not suggest strong CV safety issues, although no firm conclusions can be drawn. In particular, evidence on stroke risk is conflicting. However, if an increase of the absolute stroke risk in recently exposed patients does actually exist, it must be small. Overall, residual uncontrolled confounding factors reduce the confidence in the risk estimates collected from the included studies. Further investigations are needed to better define the risk for rare but serious CV events related to triptan and ergotamine use for treatment of migraine.

Very low-protein diet plus ketoacids in chronic kidney disease and risk of death during end-stage renal disease: a historical cohort controlled study.

BACKGROUND: Very low-protein intake during chronic kidney disease (CKD) improves metabolic disorders and may delay dialysis start without compromising nutritional status, but concerns have been raised on a possible negative effect on survival during dialysis. This study aimed at evaluating whether a very low-protein diet during CKD is associated with a greater risk of death while on dialysis treatment. METHODS: This is an historical, cohort, controlled study, enrolling patients at dialysis start previously treated in a tertiary nephrology clinic with a very low-protein diet supplemented with amino acids and ketoacids (s-VLPD group, n = 184) or without s-VLPD [tertiary nephrology care (TNC) group, n = 334] and unselected patients [control (CON) group, n = 9.092]. The major outcome was survival rate during end-stage renal disease associated to s-VLPD treatment during CKD. The propensity score methods and Cox regression model were used to match groups at the start of dialysis to perform survival analysis and estimate adjusted hazard ratio (HR). RESULTS: In s-VLPD, TNC and CON groups, average age was 67.5, 66.0 and 66.3 years, respectively (P = 0.521) and male prevalence was 55, 55 and 62%, respectively (P = 0.004). Diabetes prevalence differed in the three groups (P < 0.001), being 18, 17 and 31% in s-VLPD, CON and TNC, respectively. A different prevalence of cardiovascular (CV) disease was found (P < 0.001), being similar in TNC and CON (31 and 25%) and higher in s-VLPD (41%). Median follow-up during renal replacement therapy (RRT) was 36, 32 and 36 months in the three groups. Adjusted HR estimated on matched propensity patients was 0.59 (0.45-0.78) for s-VLPD versus CON. Subgroup analysis showed a lower mortality risk in s-VLPD versus matched-CON in younger patients (<70 years) and those without CV disease. No significant difference in HRs was found between s-VLPD and TNC. CONCLUSION: s-VLPD during CKD does not increase mortality in the subsequent RRT period.