Secondary prevention and extreme cardiovascular risk evaluation (SEVERE-0): Prevalence of extreme cardiovascular risk in cardiological rehabilitation patients and its impact on functional improvement.

BACKGROUND AND AIMS: Patients with recent Acute Coronary Syndrome (ACS) or Chronic Coronary Syndrome (CCS) are all at very high CardioVascular (CV) risk. However, some of them are more likely to experience recurrent cardiovascular events (i.e extreme CV risk). A definition of which patients should be included in this category has been recently proposed by the European Society of Cardiology but data on its prevalence are still lacking, especially in the context of Cardiac Rehabilitation (CR). Furthermore, if this condition had an impact on the CR related functional improvement is not known. Our study has been designed to answer to both these questions. METHODS AND RESULTS: The study included 938 ACS/CCS patients who attended the CR program at the Niguarda Hospital (Milan). Extreme CV patients were defined as the presence of a previous CV events within 2 years or the presence of peripheral arteriopathy or the presence of a multivessel coronary involvement. Functional improvement was evaluated through 6-Minute Walking Test (6-MWT). As many as 26.9% of the patients had an extreme CV risk. They were older (67.8 ± 10.4 vs 64.1 ± 11.1 years; p ≤ 0.001), had a higher prevalence of CV risk factors and comorbidities and had a lower functional improvement during CR (102.9 ± 68.6 vs 138.1 ± 86.5 m; p ≤ 0.001). Extreme CV risk present a significant association with the 6-MWT results at multivariate analysis. CONCLUSION: Extreme CV risk is a very frequent condition among patients with ACS/CCS reaching the prevalence of 26.9%. Furthermore, being at extreme CV risk adversely affects the patient's functional improvement obtained during CR.

Long-term prognostic performance of cardiac magnetic resonance imaging markers versus complicated clinical presentation after an acute myocarditis.

BACKGROUND: Identifying markers associated with adverse events after acute myocarditis (AM) is relevant to plan follow-up. We assessed the prognostic performance of previously described cardiac magnetic resonance imaging (CMRI) markers and their combination: septal late gadolinium enhancement (LGE) localization and left ventricular ejection fraction (LVEF) < 50 % on baseline CMRI versus complicated clinical presentation (CCP: the presence of sustained ventricular tachycardia, or LVEF<50 % on the first echocardiogram or fulminant presentation). METHODS: We retrospectively assessed 248 AM patients (median age of 34 years, 87.1 % male) from 6 hospitals with onset of cardiac symptoms<30 days, increased troponin, and CMRI/histology consistent with myocarditis to identify those at risk of major cardiac events (cardiac death, heart transplantation, aborted sudden cardiac death, sustained ventricular tachycardia, or heart failure hospitalization). RESULTS: Thirteen patients (5.2 %) experienced at least one major cardiac event after a median follow-up of 4.7 years with a significant hazard ratio of 35 for CCP vs. 9.2 for septal LGE vs. 12.4 for LVEF<50 % on baseline CMRI (p = 0.001). CCP had the best c-index to identify patients with events: 0.836 vs. 0.786 for septal LGE and 0.762 for LVEF<50 %, while the combination of CCP plus LVEF<50 % or septal LGE has the highest c-index of 0.866. All 3 markers had high negative predictive value (NPV) of ≥0.98. CONCLUSIONS: Major cardiac events after an AM are relatively low, and CCP, septal LGE, and LVEF<50 % are significantly associated with events. These markers have especially high NPV to identify patients without events after an AM. These observations can help clinicians to monitor the patients after an AM.

Uric acid and metabolic syndrome: Importance of hyperuricemia cut-off.

BACKGROUND: The relationship between HyperUricemia (HU) and Metabolic Sindrome (MS) and if Uric Acid (UA) should be inserted into MS definitions is a matter of debate. Aim of our study was to evaluate the correlation between UA and HU with Insulin Resistance (IR) and MS in a population of hypertensive patients. HU was defined with two cut-offs (the classic one of ≥6 mg/dL for women and ≥ 7 for men; the newly proposed URRAH one with ≥5.6 mg/dL for both sexes). METHODS: We enrolled 473 Hypertensive patients followed by the Hypertension Unit of San Gerardo Hospital (Monza, Italy). IR was defined through TG/HDL ratio and NCEP-ATP-III criteria were used for MS diagnosis. RESULTS: MS was found in 33.6 % while HU affected 14.8 % of subjects according to the traditional cut-off and 35.9 % with the URRAH cut-off. 9.7 % (traditional cut-off) and 17.3 % (URRAH's threshold) of the subjects had both HU and MS. UA level was significantly higher in MS group (5.7 vs 4.9 mg/dL, p < 0.0001) as well as for HU (29.0 vs 7.6 % and 51.6 vs 28.0 %, for classic and URRAH cut-off respectively, p < 0.0001 for both comparison). Logistic multivariable regression models showed that UA is related to MS diagnosis (OR = 1.608 for each 1 mg/dL), as well as HU with both cut-off (OR = 5.532 and OR = 3.379, p < 0.0001 for all comparison, for the classic cut-off and the URRAH one respectively). CONCLUSIONS: The main finding of our study is that UA and HU significantly relate to IR and MS. The higher the values of UA and the higher the cut-off used, the higher the strength of the relationship.

Hyperuricemia in Cardiac Rehabilitation Patients: Prevalence and Association with Functional Improvement and Left Ventricular Ejection Fraction.

INTRODUCTION: The role of uric acid (UA) and Hyper Uricemia (HU) in cardiac rehabilitation (CR) patients have been very little studied. AIM: To evaluate the prevalence of HU and if it is associated to the functional improvement obtained or the left ventricular Ejection Fraction (EF) in CR patients after Acute or Chronic Coronary Syndrome (ACS and CCS respectively). METHODS: We enrol 411 patients (62.4 ± 10.2 years; males 79.8%) enrolled in the CR program at Niguarda Hospital (Milan) from January 2012 to May 2023. HU was defined both as the classic cut-off (> 6 for females, > 7 mg/dL for males) and with the newly identified one by the URRAH study (> 5.1 for females, > 5.6 mg/dL for males). All patients performed a 6MWT and an echocardiography at the beginning and at the end of CR program. RESULTS: Mean UA values were within the normal range (5.6 ± 1.4 mg/dL) with 19.5% (classic cut-off) HU patients with an increase to 47.4% with the newer one. Linear regression analysis showed no role for UA in determining functional improvement, while UA and hyperuricemia (classic cut-off) were associated to admission and discharge EF. The same was not with the URRAH cut-off. CONCLUSIONS: HU is as frequent in CR patients as in those with ACS and CCS. UA didn't correlate with functional recovery while it is associated with admission and discharge EF as also is for HU (classic cut-off). Whit the URRAH cut-off HU prevalence increases significantly, however, it doesn't show any significant association with EF.

Cardiac amyloidosis red flags: What all the cardiologist have to know.

Cardiac amyloidosis is becoming increasingly important among cardiologist and an early diagnosis is very important. Amyloidosis is a systemic disease and many cardiac and extracardiac elements (red flags) should raise the suspicion of the disease. Electrocardiographic and imaging techniques (such as echocardiography, cardiac magnetic resonance and scintigraphy) are useful tools to make a diagnosis together with the presence of orthopedic issues, peripheral neuropathy or plasma cell dyscrasia. Cardiac amyloidosis is also often associated with valvular disorder, heart failure or cardiomyopathy. Red flags are crucial to raise suspicion and reach an early diagnosis, in order to start a targeted treatment strategy that could change the patient's outcome. Indeed, in the last years four new drugs were approved to treat transthyretin amyloidosis.

Arrhythmic Risk Stratification in Cardiac Amyloidosis: A Review of the Current Literature.

Cardiac amyloidosis is the most frequent infiltrative disease caused by the deposition of misfolded proteins in the cardiac tissue, leading to heart failure, brady- and tachyarrhythmia and death. Conduction disorders, atrial fibrillation (AF) and ventricular arrhythmia (VA) significantly impact patient outcomes and demand recognition. However, several issues remain unresolved regarding early diagnosis and optimal management. Extreme bradycardia is the most common cause of arrhythmic death, while fast and sustained VAs can be found even in the early phases of the disease. Risk stratification and the prevention of sudden cardiac death are therefore to be considered in these patients, although the time for defibrillator implantation is still a subject of debate. Moreover, atrial impairment due to amyloid fibrils is associated with an increased risk of AF resistant to antiarrhythmic therapy, as well as recurrent thromboembolic events despite adequate anticoagulation. In the last few years, the aging of the population and progressive improvements in imaging methods have led to increases in the diagnosis of cardiac amyloidosis. Novel therapies have been developed to improve patients' functional status, quality of life and mortality, without data regarding their effect on arrhythmia prevention. In this review, we consider the latest evidence regarding the arrhythmic risk stratification of cardiac amyloidosis, as well as the available therapeutic strategies.

[Contemporary diagnosis and treatment of tricuspid regurgitation: from neglected valve to primetime]. / Diagnosi e trattamento contemporaneo dell'insufficienza tricuspidale: da valvola dimenticata a primetime.

Tricuspid insufficiency has long been considered an entity with low prognostic importance and associated with symptoms and signs only secondarily to left heart pathology. Scientific research in recent years has debunked this myth, demonstrating a key role in determining symptoms and signs of right heart failure, even in advanced stages. In parallel, advances in transcatheter technologies have opened up treatment options even for patients with increased surgical risk, who were previously excluded from traditional surgical options, with increasingly convincing results in reducing symptoms and improving the quality of life of our patients. The contemporary challenge is to translate these messages into everyday clinical practice and to encourage the centralization of patients in centers that currently have the expertise for feasibility evaluation and subsequent treatment. In this Review, we will analyze the most recent evidence on the pathophysiology and diagnosis of tricuspid insufficiency, the latest recommendations from European guidelines, and we will try to illustrate the most common technologies for percutaneous treatment and the abundant evidence supporting them.

Risk of Cardiovascular Events in Metabolically Healthy Overweight or Obese Adults: Role of LDL-Cholesterol in the Stratification of Risk.

The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged <70 years, high BMI was associated with an increased risk of MACE, whereas among the older subjects it was associated with lower risk. Compared to the group with normal weight/healthy metabolic status, the metabolically healthy participants aged <70 years who were overweight/obese had an increased risk of MACE with an adjusted hazard ratio of 3.81 (95% CI, 1.34-10.85, p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07-6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

H2FPEF and HFA-PEFF scores performance and the additional value of cardiac structure and function in patients with atrial fibrillation.

BACKGROUND: The H2FPEF and the HFA-PEFF scores have become useful tools to diagnose heart failure with preserved ejection fraction (HFpEF). Their accuracy in patients with a history of atrial fibrillation (AF) is less known. This study evaluates the association of these scores with invasive left atrial pressure (LAP) and the additional value of cardiac measures. METHODS: This is a multicenter observational prospective study involving patients undergoing ablation of AF. Patients with left ventricular ejection fraction (LVEF) < 40%, congenital cardiopathy, any severe cardiac valve disease and prosthetic valves were excluded. Elevated filling pressure was defined as a mean LAP ≥15 mmHg. RESULTS: A total of 135 patients were enrolled in the study (mean age 65.2 ± 9.1 years, 32% female, mean LVEF 56.9 ± 7.9%). Patients with H2FPEF ≥ 6 or HFA-PEFF ≥5 had higher values of NTproBNP and more impaired cardiac function. However, neither H2FPEF nor HFA-PEFF score showed a meaningful association with elevated mean LAP (respectively, OR 1.05 [95%CI 0.83-1.34] p = 0.64, and OR 1.09 [95%CI: 0.86-1.39] p = 0.45). The addition of LA indexed minimal volume (LAVi min) improved the ability of the scores (baseline C-statistic 0.51 [95%CI 0.41-0.61] for the H2FPEF score and 0.53 [95%CI 0.43-0.64] for the HFA-PEFF score) to diagnose elevated filling pressure (H2FPEF + LAVi min: C-statistic 0.70 [95%CI 0.60-0.80], p-value = 0.005; HFA-PEFF + LAVi min: C-statistic 0.70 [95%CI 0.60-0.80], p-value = 0.02). CONCLUSION: In a cohort of patients with a history of AF, the use of the available diagnostic scores did not predict elevated mean LAP. The integration of LAVi min improved the ability to correctly identify elevated filling pressure.

May Measure Month 2022 in Italy: A Focus on Fixed-dose Combination, Therapeutic Adherence, and Medical Inertia in a Nationwide Survey.

INTRODUCTION: Hypertension is the main risk factor for cardiovascular diseases (CVD). Notably, only about half of hypertensive patients manage to achieve the recommended blood pressure (BP) control. Main reasons for the persistence of uncontrolled BP during treatment are lack of compliance on the patients' side, and therapeutic inertia on physicians' side. METHODS: During the global BP screening campaign "May Measure Month" (MMM) (May 1st to July 31st, 2022), a nationwide, cross-sectional, opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of the health issues surrounding high BP. A questionnaire on demographic/clinical features and questions on the use of fixed-dose single-pills for the treatment of hypertension was administered. BP was measured with standard procedures. RESULTS: A total of 1612 participants (mean age 60.0±15.41 years; 44.7% women) were enrolled. Their mean BP was 128.5±18.1/77.1±10.4 mmHg. About half of participants were sedentary, or overweight/obese, or hypertensive. 55.5% individuals with complete BP assessment had uncontrolled hypertension. Most were not on a fixed-dose combination of antihypertensive drugs and did not regularly measure BP at home. Self-reported adherence to BP medications was similar between individuals with controlled and uncontrolled BP (95% vs 95.5%). CONCLUSIONS: This survey identified a remarkable degree of therapeutic inertia and poor patients' involvement in the therapeutic process and its monitoring in the examined population, underlining the importance of prevention campaigns to identify areas of unsatisfactory management of hypertension, to increase risk factors' awareness in the population with the final purpose of reducing cardiovascular risk.

Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27], p < 0.001 and HR 1.25 [1.09-1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

The Therapy and Management of Heart Failure with Preserved Ejection Fraction: New Insights on Treatment.

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterised by the presence of diastolic dysfunction and elevated left ventricular filling pressure, in the setting of a left ventricular ejection fraction of at least 50%. Despite the epidemiological prevalence of HFpEF, a prompt diagnosis is challenging and many uncertainties exist. HFpEF is characterised by different phenotypes driven by various cardiac and non-cardiac comorbidities. This is probably the reason why several HFpEF clinical trials in the past did not reach strong outcomes to recommend a single therapy for this syndrome; however, this paradigm has recently changed, and the unmet clinical need for HFpEF treatment found a proper response as a result of a new class of drug, the sodium-glucose cotransporter 2 inhibitors, which beneficially act through the whole spectrum of left ventricular ejection fraction. The aim of this review was to focus on the therapeutic target of HFpEF, the role of new drugs and the potential role of new devices to manage the syndrome.

Cardiovascular Structural and Functional Parameters in Idiopathic Pulmonary Fibrosis at Disease Diagnosis.

INTRODUCTION: Prevalence of cardiac and vascular fibrosis in patients with Idiopathic Pulmonary Fibrosis (IPF) has not been extensively evaluated. AIM: In this study, we aimed to evaluate the heart and vessels functional and structural properties in patients with IPF compared to healthy controls. An exploratory analysis regarding disease severity in IPF patients has been done. METHODS: We enrolled 50 patients with IPF (at disease diagnosis before antifibrotic therapy initiation) and 50 controls matched for age and gender. Heart was evaluated through echocardiography and plasmatic NT-pro-brain natriuretic peptide that, together with patients' symptoms, allow to define the presence of Heart Failure (HF) and diastolic dysfunction. Vessels were evaluated through Flow Mediated Dilation (FMD - endothelial function) and Pulse Wave Velocity (PWV-arterial stiffness) RESULTS: Patients with IPF had a prevalence of diastolic disfunction of 83.8%, HF of 37.8% and vascular fibrosis of 76.6%. No statistically significant difference was observed in comparison to the control group who showed prevalence of diastolic disfunction, HF and vascular fibrosis of 67.3%, 24.5% and 84.8%, respectively. Disease severity seems not to affect PWV, FMD, diastolic dysfunction and HF. CONCLUSIONS: Patients with IPF early in the disease course do not present a significant CV fibrotic involvement when compared with age- and sex-matched controls. Bigger and adequately powered studies are needed to confirm our preliminary data and longitudinal studies are required in order to understand the time of appearance and progression rate of heart and vascular involvement in IPF subjects.

Prevalence, Clustering, and Current Management of Cardiovascular Risk Factors Upon First Referral to Hypertension Specialists: the APPROACH Study.

INTRODUCTION: Several observational studies have been conducted to assess the prevalence of cardiovascular risk factors in hypertensive patients; however, none has yet investigated prevalence, clustering, and current management of cardiovascular risk factors upon first referral to hypertension specialists, which is the aim of the present study. METHODS: Consecutive adult outpatients with essential/secondary hypertension were included at the time of their first referral to hypertension specialists at 13 Italian centers in the period April 2022-2023 if they had at least one additional major cardiovascular risk factor among LDL-hypercholesterolemia, type 2 diabetes, and cigarette smoking. Prevalence, degree of control, and current management strategies of cardiovascular risk factors were assessed. RESULTS: A total of 255 individuals were included, 40.2% women and 98.4% Caucasian. Mean age was 60.3±13.3 years and mean blood pressure [BP] was 140.3±17.9/84.8±12.3 mmHg). Most participants were smokers (55.3%), had a sedentary lifestyle (75.7%), suffered from overweight/obesity (51%) or high LDL-cholesterol (41.6%), had never adopted strategies to lose weight (55.7%), and were not on a low-salt diet (57.4%). Only a minority of patients reported receiving specialist counseling, and 27.9% had never received recommendations to correct unhealthy lifestyle habits. Nearly 90% of individuals with an estimated high/very high cardiovascular risk profile did not achieve recommended LDL-cholesterol targets. CONCLUSIONS: In patients with hypertension, both pharmacological and lifestyle therapeutic advice are yet to improve before referral to hypertension specialists. This should be considered in the primary care setting in order to optimize cardiovascular risk management strategies.

Contemporary Advances in Cardiac Remote Monitoring: A Comprehensive, Updated Mini-Review.

Over the past decade, remote monitoring (RM) has become an increasingly popular way to improve healthcare and health outcomes. Modern cardiac implantable electronic devices (CIEDs) are capable of recording an increasing amount of data related to CIED function, arrhythmias, physiological status and hemodynamic parameters, providing in-depth and updated information on patient cardiovascular function. The extensive use of RM for patients with CIED allows for early diagnosis and rapid assessment of relevant issues, both clinical and technical, as well as replacing outpatient follow-up improving overall management without compromise safety. This approach is recommended by current guidelines for all eligible patients affected by different chronic cardiac conditions including either brady- and tachy-arrhythmias and heart failure. Beyond to clinical advantages, RM has demonstrated cost-effectiveness and is associated with elevated levels of patient satisfaction. Future perspectives include improving security, interoperability and diagnostic power as well as to engage patients with digital health technology. This review aims to update existing data concerning clinical outcomes in patients managed with RM in the wide spectrum of cardiac arrhythmias and Hear Failure (HF), disclosing also about safety, effectiveness, patient satisfaction and cost-saving.

Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project).

PURPOSE: Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk. METHODS: The analysis included 16,649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. RESULTS: During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality, than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only one of the two factors. CONCLUSIONS: The results of this study indicate that these TyG (a low-cost and simple non-invasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality.

Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals-The Uric Acid Right for Heart Health (URRAH) Project.

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

BACKGROUND: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort. METHODS AND RESULTS: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P=0.004) and 1.150 (95% CI, 1.021-1.295, P=0.02), respectively. CONCLUSIONS: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.