Excess Risk Of Cardiovascular Events Research Articles

Clinical Management of Primary Aldosteronism: An Update.

Despite carrying an excess risk of cardiovascular events, primary aldosteronism (PA) is a commonly overlooked secondary form of arterial hypertension. An increased awareness of its high prevalence and broader screening strategies are urgently needed to improve its detection rate and allow early diagnosis and targeted treatment. For patients with unilateral PA, these measures can correct hyperaldosteronism and ensure cure of hypertension, even when resistant to drug treatment, thus preventing adverse cardiovascular events. Among these, atrial fibrillation is the most common, but left ventricular hypertrophy, stroke, chronic kidney disease, and myocardial infarction also occur more often than in patients with hypertension and no PA. Young patients, who have higher chances of being cured long term, and high-risk patients, such as those with stage III or resistant hypertension, are those who will benefit most from an early diagnosis of PA. Therefore, the implementation of strategies to detect PA by a simplified diagnostic algorithm is necessary. In the patients who seek for surgical cure, adrenal vein sampling is key for the identification of unilateral PA and the achievement of optimal outcomes. Unfortunately, being technically demanding and poorly available, adrenal vein sampling represents the bottleneck in the workup of PA. Considering the novel knowledge generated in the past 5 years in many studies, particularly in the AVIS-2 study (Adrenal Vein Sampling International Study-2), based on 4 decades of experience at our center and on the last guidelines, we herein provide an update on the management of PA with recommendations for drug treatment and strategies to avoid adrenal vein sampling wherever it is poorly, or not, available.

Adjudicated cardiovascular events in a cotemporary multicenter cohort of patients with COVID-19: findings from the CORONA-VTE Registry

Abstract Background Coronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular events in the early post-infection period and during convalescence. Despite the progress in our understanding of cardiovascular complications, uncertainty persists with respect to contemporary event rates particularly given the change in viral variants and COVID-19 therapies, as well as availability of vaccines in later months of the pandemic. Purpose To report the cardiovascular complications of COVID-19, and assess results by vaccination status from a large multicenter patient-level US registry. Methods Adult patients with polymerase chain reaction-confirmed COVID-19 who received inpatient or outpatient care at Mass-General Brigham (MGB) Health system, the largest health system in Massachusetts that serves 1.5 million patients, were eligible for inclusion. Data elements were entered into a centralized database by trained research staff. Each clinical event was adjudicated by two independent physicians. The primary outcome was major cardiovascular events, defined as venous or arterial thrombosis, myocarditis or heart failure with inpatient treatment, new atrial fibrillation/flutter, or cardiovascular death. Outcomes were assessed at 30- and 90-day follow-up, shown as cumulative incidence, represented by subdistribution hazard functions. Findings were pre-specified to be assessed separately for patients who were hospitalized with COVID-19 vs outpatients. Vaccination status was ascertained for subgroup-specific analyses. Results The study included 4,123 patients from the MGB Health System from 3/13/2020 through 06/03/2022 (mean age: age: 53.5 ± 18 years; 55.9% female, Table). Among hospitalized patients, the cumulative incidence of primary outcome was 17.4% at day 30 (95% CI: 15.2-19.5%). Respective 30-day event rates for outpatients were 1.1% (95% CI: 0.7%-1.5%) (Figure, Panel A). Cumulative incidence of 30-day outcomes based on vaccination status (restricted to cohort from 12/14/2020 onward) is summarized in Panel B. Conclusions This multicenter study suggests that 30-day adjudicated cardiovascular events were frequent in hospitalized patients with COVID-19, although event rates were lower in vaccinated patients. Follow-up for 90-day outcomes is being finalized and will be presented at ESC 2023.Table 1.Figure 1.

Abstract 17286: Ninety-Day Adjudicated Cardiovascular Events in Patients With Covid-19: Association With Vaccination Status and Changes Over Time in the Corona-VTE Network Study

Background: Coronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular events. Despite the progress in our understanding of cardiovascular complications, uncertainty persists with respect to contemporary event rates, and the association between use of vaccines and outcomes, and changes in incidence rates over time. Methods: Adult patients with polymerase chain reaction-confirmed COVID-19 who received care at Mass General-Brigham health system, Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System were included. The Brigham and Women’s Hospital served as the central coordinating center. Clinical events were adjudicated by independent physicians. The primary outcome was 90-day major cardiovascular events, defined as venous or arterial thrombosis, myocarditis or heart failure with inpatient treatment, new atrial fibrillation/flutter, or cardiovascular death. Findings were pre-specified to be assessed separately for patients who were hospitalized with COVID-19 vs outpatients. Results: The study included 9,932 patients (03/2020-06/2022, age: 54.8 ± 19.9 years; 55.7% female). Among hospitalized patients, the 90-day cumulative incidence of primary outcome was 15.4 % (95% CI: (14.2-16.7%). Respective 90-day event rates for outpatients were 2.0% (95% CI: 1.3-15.7%) (Figure, Panel A). Cumulative incidence of 90-day outcomes based on vaccination status (restricted to cohort from 12/14/2020 onward) is summarized in Panel B. The change in cardiovascular events over time is represented in Figure, Panel C. Conclusions: Adjudicated cardiovascular events are common in hospitalized patients with COVID-19, while the event rates are seven-fold lower among outpatients. Association between vaccination status and outcomes and trends over time require further investigation.

Excess risk of cardiovascular events in patients in the United States vs. Japan with chronic kidney disease is mediated mainly by left ventricular structure and function

While patients receiving dialysis therapy in the United States are more likely to develop cardiovascular disease (CVD) than those in Japan, direct comparisons of patients with predialysis chronic kidney disease (CKD) are rare. To study this, we compared various outcomes in patients with predialysis CKD using data from the Chronic Renal Insufficiency Cohort (CRIC) and CKD Japan Cohort (CKD-JAC) studies and determined mediators of any differences. Candidate mediators included left ventricular (LV) indices assessed by echocardiography. Among 3125 CRIC and 1097 CKD-JAC participants, the mean LV mass index (LVMI) and ejection fraction (EF) were 55.7 and 46.6 g/m2 and 54% and 65%, respectively (both significant). The difference in body mass index (32 and 24 kg/m2, respectively) largely accounted for the differences in LVMI and C-reactive protein levels across cohorts. Low EF and high LVMI were significantly associated with subsequent CVD in both cohorts. During a median follow-up of five years, CRIC participants were at higher risk for CVD (adjusted hazard ratio [95% confidence interval]: 3.66 [2.74-4.89]) and death (4.69 [3.05-7.19]). A three-fold higher C-reactive protein concentration and higher phosphate levels in the United States cohort were moderately strong mediators of the differences in CVD. However, echocardiographic parameters were stronger mediators than these laboratory measures. LVMI, EF and their combination mediated the observed difference in CVD (27%, 50%, and 57%, respectively) and congestive heart failure (33%, 62%, and 70%, respectively). Thus, higher LV mass and lower EF, even in the normal range, were found to be predictive of CVD in CKD.

Gender Differences in the Risk of Adverse Outcomes After Incident Diabetic Foot Hospitalization: A Population Cohort Study.

Diabetic Foot Disease (DFD) is more prevalent among males and is associated with an excess risk of cardiovascular events or mortality. This study aimed at exploring the risk of cardiovascular events, renal failure, and all-cause mortality after incident DFD hospitalizations, separately in males and females, to detect any gender difference in a cohort of 322,140 people with diabetes retrospectively followed up through administrative data sources in Tuscany, Italy, over the years 2011-2018. The Hazard Ratio (HR) for incident adverse outcomes after first hospitalizations for DFD, categorized as major/minor amputations (No.=449;3.89%), lower limbs' revascularizations (LLR: No.=2854;24.75%), and lower-extremity-arterial-disease (LEAD) with no procedures (LEAD-no proc: No.=6282;54.49%), was compared to the risk of patients having a background of DFD (ulcers, infections, Charcot-neuroarthropathy: No.=1,944;16.86%). DFD incidence rate was higher among males compared to females (1.57(95% CI:1.54-1.61) vs. 0.97(0.94-1.00)/100,000p-years]. After DFD, the overall risk of coronary artery disease was significantly associated with the male gender and of stroke with the female gender. LEAD-no proc and LLR were associated with the risk of stroke only in females, whereas they were found to be associated with the risk of coronary artery disease among females to a significantly greater extent compared to males. The incident of renal failure was not associated with any DFD category. Amputations and LEAD-no proc significantly predicted high mortality risk only in females, while LLR showed reduced risk in both genders. Moreover, females had a greater risk of composite outcomes (death or cardiovascular events). Compared to the background of DFD, the risk was found to be 34% higher after amputations (HR: 1.34(1.04-1.72)) and 10% higher after LEAD-no proc (HR:1.10(1.03-1.18)), confirming that after incident DFD associated with vascular pathogenesis, females are at an increased risk of adverse events. After incident DFD hospitalizations, females with DFD associated with amputations or arterial disease are at a greater risk of subsequent adverse cardiovascular events than those with a DFD background.

High ankle brachial index predicts high risk of cardiovascular events amongst people with peripheral artery disease.

Ankle-brachial pressure index (ABPI) is commonly measured in people referred to vascular specialists. This study aimed to assess the association of high ABPI (≥ 1.4) with cardiovascular events in people with peripheral artery disease (PAD). 1533 participants with PAD diagnosed by a vascular specialist were prospectively recruited from four out-patient clinics in Australia. ABPI was measured at recruitment and the occurrence of myocardial infarction (MI), stroke or cardiovascular death (major cardiovascular events; MACE) and any amputation were recorded over a median (inter-quartile range) follow-up of 3.3 (1.0–7.1) years. The association of high, compared to normal, low (0.5–0.9) or very low (<0.5), ABPI with clinical events was estimated using Cox proportional hazard analyses, adjusting for traditional risk factors and reported as hazard ratio with 95% confidence intervals. 596 (38.9%), 676 (44.1%), 157 (10.2%) and 104 (6.8%) participants had normal, low, very low and high ABPI, respectively. Participants with high ABPI had increased risk of MACE, MI and death by comparison to those with either normal ABPI [1.69 (1.07, 2.65), 1.93 (1.07, 3.46) and 1.67 (1.09, 2.56)] or either low or very low ABPI [1.51 (1.02, 2.23), 1.92 (1.16, 3.19) and 1.47 (1.02, 2.14)] after adjusting for other risk factors. Findings were similar in a sensitivity analysis excluding people with ABPI only measured in one leg (n = 120). Participants with high ABPI also had an increased risk of MACE and MI compared to those with very low ABPI alone. High ABPI is a strong indicator of excess risk of cardiovascular events amongst people with PAD.

Similar risk of cardiovascular events in idiopathic inflammatory myopathy and rheumatoid arthritis in the first 5\xa0years after diagnosis

ObjectivesTo estimate the incidence of cardiovascular (CV) events in idiopathic inflammatory myopathy (IIM) compared to patients with rheumatoid arthritis (RA) and the general population. To explore the contribution of traditional CV risk factors to any difference observed.MethodsA retrospective matched population-based cohort study was conducted using UK Clinical Practice Research Datalink (CPRD) from 1987 to 2013. The incidence of CV events was calculated for each cohort over time and compared using Cox proportional hazards models. Multivariable analyses were used to adjust for traditional CV risk factors.ResultsA total of 603 patients with IIM 4047 RA and 4061 healthy controls were included. The rate of CV events in IIM was significantly greater than healthy controls [hazard ratio (HR) 1.47 (95% confidence interval (CI) 1.18–1.83)] and remained significant after adjustment for CV risk factors [HR 1.38 (95% CI 1.11–1.72)]. Risk was similar between IIM and RA [HR 1.01 (95% CI 0.78–1.31)]. The rate of myocardial infarction [HR 1.61 (95% CI 1.27–2.04)] but not stroke [HR 0.92 (95% CI 0.59–1.44)] was significantly greater in IIM compared to healthy controls. After the first 5 years, the rate of CV events for RA remained significantly greater compared to the control group, but appeared to return to that of the healthy controls in the IIM group.ConclusionIIM is associated with an increased risk of CV events in the first 5 years after diagnosis similar to that of RA. Beyond 5 years, the risk appears to return to that of the general population in IIM but not RA.Key Points• The excess risk of cardiovascular events in IIM is similar to that found in RA.• The excess risk of cardiovascular events is greatest in the first 5 years after diagnosis.

Incidence of New-Onset Diabetes and PostTransplant Metabolic Syndrome after Liver Transplantation - A Prospective Study from South India.

Background and Aims:Liver transplantation has become an effective therapy for patients with end-stage liver disease. The risk of new-onset diabetes after transplantation (NODAT) and posttransplant metabolic syndrome (PTMS) is high among patients after liver transplantation. These are thought to be associated with increased risks of graft rejection, infection, cardiovascular disease, and death. Our study aimed to document the incidence of NODAT and PTMS and analyze pre and posttransplant predictive factors for their development in patients undergoing a liver transplant.Methods:This was a prospective comparative study on 51 patients who underwent live donor liver transplantation. They were evaluated at baseline, 3 and 6 months after transplantation with fasting glucose, lipids, serum insulin levels, C-peptide, and HbA1C. They were followed up at 5 years to document any cardiovascular events or rejection.Results:The incidence of preoperative diabetes mellitus (DM) in the study group was 25/51 (49%). The incidence of NODAT was 38.5% (10/26 patients) and PTMS 29% (10/35), respectively. Age (47.7 ± 5.4 vs 41.5 ± 12.7 years), HOMA2 - IR (2.3 ± 1.8 vs 2.1 ± 1.6), serum insulin (16.1 ± 12.0 vs 17.9 ± 14.5), and C-peptide (4.6 ± 0.5 vs 4.8 ± 0.7) were similar at baseline in the NODAT group compared to those who did not develop it. Mean tacrolimus levels were higher in PTMS group (6.8 ± 2.9 vs 5.0. ± 2.0 P value = 0.042). By the end of 5 years, 7 patients expired; 6 due to rejection and one due to cardiovascular disease. Moreover, 2 of these patients had preexisting DM and 2 had NODAT.Conclusions:None of the baseline metabolic factors in patients undergoing liver transplant were predictive of the development of NODAT or PTMS. Mean tacrolimus levels were significantly higher in the PTMS group. A 5-year follow-up showed no excess risk of cardiovascular events or rejection in those with preexisting DM or in those who developed NODAT.

Manažment hyperlipidémie na Slovensku: observačná štúdia

A multicountry observational study was conducted to gain insight into the current management of elevated low density lipoprotein cholesterol (LDL-C) in high-risk (HR) and very high-risk (VHR) patients with hyperlipidaemia across central and eastern Europe and Israel. Here we present data from the Slovakian subpopulation.We enrolled adult patients who were receiving lipid-lowering therapy (LLT) and attending a specialist (cardiologist/diabetologist/internist) for a routine visit at 9 sites (including academic/specialist centers) across Slovakia. Data were collected retrospectively from patients records for the 12 months preceding enrolment.150 patients, mean (range) age 62.8 (26-84) years were enrolled, including 24 with familial hypercholesterolemia and 109 secon-dary prevention patients. Almost all patients (147; 98.0 %) were receiving statins, as monotherapy (114; 76.0 %) or in combination with other LLT (33; 22.0 %): 11 (7.3 %) were classified as having statin intolerance symptoms. Mean LDL-C levels were 3.0 (1.1-7.1) mmol/l at the first, and 2.6 (0.7-7.7) mmol/l at the last, visit of the observation period. Only 2/16 (12.5 %; 95 % CI 1.6-38.4 %) HR patients and 40/134 (29.9 %; 22.3-38.4 %) VHR patients achieved their recom-mended LDL-C targets of &lt; 2.5 and &lt; 1.8 mmol/l, respectively, during observation. In the FH subset 2/15 (13.3 %; 1.7-40.5 %) HR and 2/9 (22.2 %; 2.8-60.0 %) VHR patients achieved these targets. In patients with definite/probable FH (Dutch Lipid Clinic Network score 6), these targets were attained by 2/15 (13.3 %; 1.7-40.5) HR patients and 0/6 VHR patients. A total of 41 patients (27.3 %) experienced CV events ( 3) during the 12-month observation period.Our findings provide a picture of patients treated for hyperlipidemia across Slovakia. We found that, despite widespread statin use, a substantial proportion of patients, particularly those with FH, are undertreated and fail to achieve the LDL-C targets recommended in European guidelines. They consequently remain at excess risk of cardiovascular events.

Excess risk estimation for matched cohort survival data.

We present an excess risk regression model for matched cohort data, where the occurrence of some events for individuals with a disease is compared to that of healthy controls that are matched at the onset-of-disease by various factors. By using the matched structure, we show how to estimate the excess risk and its dependence on covariates on both proportional and additive form. We remove the individual effects on background mortality related to matching factors by considering differences. The model handles two different time scales, namely attained age and follow-up time. First, we solve estimating equations for the non-parametric and parametric components of the excess risk model, providing large sample properties for the suggested estimators. Next, we report results from a simulation study. Lastly, we describe an application of the method on childhood cancer data, to study the excess risk of cardiovascular events in adults' life among childhood cancer survivors.

Impact of Chamber Dilatation on the Prognostic Value of Left Ventricular Geometry in Hypertension.

BackgroundThe different geometric patterns of the left ventricle may or may not coexist with chamber dilatation. The prognostic impact of such a combination is unclear.Methods and ResultsWe studied a cohort of 2635 initially untreated patients with hypertension, mean age 50 years. At entry, 24‐hour ambulatory blood pressure progressively increased across the patterns of normal geometry, concentric left ventricular (LV) remodeling, eccentric nondilated LV hypertrophy (LVH), eccentric dilated LVH, concentric nondilated LVH, and concentric dilated LVH. During a mean follow‐up of 9.7 years, 360 patients developed a first major cardiovascular event at a rate (×100 patient‐years) of 1.41. The event rate was 0.93 in the group with normal LV geometry, 1.10 in the group with LV concentric remodeling, 1.40 in the group with nondilated eccentric LVH, 2.10 in the group with eccentric dilated LVH, 2.34 in the group with nondilated concentric LVH, and 4.67 in the group with dilated concentric LVH (log‐rank test: P<0.001). In a Cox model, after adjustment for several independent covariables (age, sex, diabetes mellitus, current smoking, total cholesterol, estimated glomerular filtration rate, and average 24‐hour systolic blood pressure), concentric dilated LVH was associated with a 98% excess risk of cardiovascular events (P=0.0037). However, LV geometric pattern lost statistical significance when LV mass was entered into the model.ConclusionsIn initially untreated patients with hypertension, LV dilatation adds an adverse prognostic burden to the patterns of eccentric and concentric LVH. This phenomenon is explained by the greater LV mass associated with LV chamber dilatation.

Gender difference in diabetes related excess risk of cardiovascular events: When does the ‘risk window’ open?

ObjectiveWomen with diabetes have a greater excess risk for cardiovascular diseases (CVD) than men. This study was aimed at clarifying whether this effect is lifelong or more evident in some life-periods. MethodsThe effect of diabetes and gender on the risk of first ever hospitalization for acute myocardial infarction (AMI), ischemic stroke (IS), congestive heart failure (CHF), lower extremity amputations (LEA) or any of these major cardiovascular events (MACE) have been evaluated by a Cox-hazard model, over years 2008–2012 querying administrative databases of a cohort living in Tuscany, Italy. ResultsComparing subjects with diabetes to those without it the overall age-adjusted excess risk was higher in women than in men for AMI and MACE and higher in men for LEA, with no difference for IS or CHF. In women the excess risk for AMI and MACE started earlier (46yr) and lasted until age of more than 85yr, while ‘risk-windows’ opened later and had a shorter duration for CHF (56–65yr) and IS (66–75yr). ConclusionDiabetic women have a significant diabetes-associated excess of CVD risk, except for LEA, with a ‘risk window’ opening earlier and lasting longer for AMI and MACE, later and with a shorter duration for IS and CHF.

Prevalence of Elevated Blood Pressure in HIV-infected Children, Adolescents and Young Adults.

To the Editor: We read with interest the recently published article by Chatterton-Kirchmeier et al1 describing an increased prevalence of high blood pressure (HBP) in HIV-infected youths in the United States. Vertically, HIV-infected subjects appear to show excess risk of cardiovascular events, and we agree with the authors that prompt management of cardiovascular disease risk factors in this population is warranted, although it is frequently overlooked by pediatricians. The prevalence of hypertension reported by Chatterton-Kirchmeier et al,1 however, exceeds the data observed in other cohorts of HIV-infected youths and deserves comment. In 2011, our group enrolled 150 HIV-infected youths and 150 controls in a longitudinal follow-up cohort study addressing cardiovascular risk factors in Madrid.2 Mean age was 14.8 years (range, 2.5–24), and most were Caucasian vertically infected adolescents. Intima-media thickness (IMT), blood pressure (BP) and lipid and glycemic profiles were measured. After adjustment for sex, age and height, the median value of 3 BP measurements was used for diagnosis of hypertension. There was a 2.7% prevalence among HIV+, with no significant differences between HIV-infected and -uninfected controls. Nevertheless, IMT was increased in HIV-infected participants (0.43 vs. 0.42 mm, P = 0.001). Cardiovascular disease in HIV-infected patients might be related to accelerated atherosclerosis, most probably secondary to a series of factors, including direct viral effects, chronic inflammation, T-cell and monocyte activation and antiretroviral treatment-associated metabolic alterations.3 Although several studies have shown increased carotid IMT among HIV-infected children, reported BP values are typically similar to those observed in control subjects.2,4 Chatterton-Kirchmeier et al1 reported a prevalence of hypertension of 19.6% among 107 HIV-infected subjects 2–17 years old. These findings were based on a single BP measurement recorded in medical charts, adjusted for sex, age and height. Because repeated BP measurements in different occasions are widely recommended for the diagnosis of hypertension, we believe that these data must be interpreted very cautiously. Furthermore, the particular characteristics of this cohort might challenge the extrapolation of these findings to other populations. Almost 90% of the study participants were of African American ethnicity, a well-established risk factor for hypertension.5 Fifty-seven percent were male, and the prevalence of cardiovascular risk factors such as tobacco use or obesity (24% and 29%, respectively) was higher than in other cohorts.2,4 Overall, the incidence of past medical conditions associated with HBP was 17%. Exposure of this population to a greater burden of cardiovascular risk factors compared with what has been typically found in other HIV-infected populations is likely to confound the role of HIV infection as a determinant of hypertension. Besides, 33.8% of participants had acquired HIV horizontally, with a mean age of 17.8 years at recruitment, which necessarily implies a short-term exposure to the potential deleterious effects of HIV and antiretroviral treatment. Therefore, based on data from our group and others,1–4 we think that cardiovascular risk factors, and among them BP, should be aggressively sought in HIV-infected subjects, as prompt diagnosis and treatment of cardiovascular disease need to be optimized during infancy and adolescence in this population. In our view, however, the evidence supporting a direct relationship between HIV and HBP remains scarce. Talía Sainz, MD, PhD Department of Pediatrics, Tropical and Infectious Diseases Unit Hospital la Paz and, La Paz Research Institute (IdiPAZ) Sergio Serrano-Villar, MD, PhD Infectious Diseases Department, Hospital Universitario Ramón y Cajal and IRyCIS María José Mellado, MD, PhD Department of Pediatrics, Tropical and Infectious Diseases Unit Hospital la Paz and La Paz Research Institute (IdiPAZ), Madrid, Spain

Antihypertensive Drugs, Hypotension, and Ischemic Colitis

In this issue of the journal, Hines et al. [1] report incidence rates of ischemic colitis in treated hypertensive adults in the USA, with a focus on aliskiren, a direct renin inhibitor. While these investigators are to be commended for assessing such a large dataset (2,356,226 hypertensive patients), they provide no clear explanation for the focus on aliskiren. The ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) trial, which concerned patients with type 2 diabetes and chronic kidney disease or cardiovascular disease, was stopped prematurely because of a slight excess risk of cardiovascular events in patients receiving aliskiren plus an angiotensin receptor blocker (ARB) or angiotensinconverting enzyme inhibitor (ACEI) compared with those receiving placebo plus an ARB or ACEI. This study also demonstrated a significantly higher risk of renal impairment, hypotension, and hyperkalemia in the aliskiren group [2]. Consequently, the US FDA modified the labeling of aliskiren in April 2012 with a new contraindication against the use of aliskiren with ARBs or ACEIs in patients with diabetes, and a warning to avoid the use of aliskiren with ARBs or ACEIs in patients with moderate to severe renal impairment [3] The European Medicines Agency (EMA) contraindicated aliskiren in both situations [4]. One and a half years later, the FDA published a new warning and precaution about symptomatic hypotension that may occur after initiation of aliskiren in patients with marked volume depletion, those with salt depletion, or those receiving other agents acting on the renin–angiotensin–aldosterone system [5]. More recently, in light of two other clinical trials and a meta-analysis [6–8], the EMA recommended against the prescription of dual reninangiotensin system blockade through the combined use of ACEIs, ARBs, or aliskiren [9] because these combinations were associated with an increased risk of hyperkalemia, kidney damage, and hypotension. Furthermore, no significant benefits from dual blockade were seen in patients without heart failure. Benefits were thought to outweigh risks only in a selected group of patients with heart failure in whom other treatments were unsuitable. Hypotension is a risk factor of ischemic colitis, an uncommon, potentially severe, and sometimes fatal disease caused by a lack of blood flow. It is also a diagnosis of exclusion with no identified cause [10, 11]. The ageand sex-adjusted incidence rate was estimated to be 22.9 per 100,000 patient-years (PYs) (95 % confidence interval [CI] 18.6–27.3) for the period 2006–2009 among unselected subjects in a US county [12]. The incidence was twice as frequent for women and increased strongly with age, from 1.1 per 100,000 PYs before the age of 40 years to 107 per 100,000 PYs for subjects aged 80 years or older [10]. In this study, the main risk factor was a hypotensive episode in the previous month (odds ratio [OR] 33.0, 95 % CI 13.3–80.9) [11]. Other independent risk factors identified were collagen vascular disease (OR 8.0, 95 % CI 2.2–28.3), peripheral vascular disease (OR 7.9, 95 % CI 4.7–13.2), congestive heart failure (OR 4.1, 95 % CI 2.6–6.3), psychotropic medications used in the past This comment refers to the article available at doi:10.1007/s40256-014-0101-4.

Mineralocorticoid Receptor Antagonists Therapy in Resistant Hypertension: Time to Implement Guidelines!

Despite the availability of anti-hypertensive medications with increasing efficacy up to 50% of hypertensive patients have blood pressure levels (BP) not at the goals set by international societies. Some of these patients are either not optimally treated or are non-adherent to the prescribed drugs. However, a proportion, despite adequate treatment, have resistant hypertension (RH), which represents an important problem in that it is associated to an excess risk of cardiovascular events. Notwithstanding a complex pathogenesis, an abundance of data suggests a key contribution for the mineralocorticoid receptor (MR) in RH, thus fostering a potential role for its antagonists in RH. Based on these premises randomized clinical trials aimed at testing the efficacy of MR antagonists (MRAs) in RH patients have been completed. Overall, they demonstrated the efficacy of MRAs in reducing BP and surrogate markers of target organ damage, such as microalbuminuria, either compared to placebo or to other drugs. In summary, owing to the key role of the MR in the pathogenesis of RH and on the proven efficacy of MRAs we advocate their inclusion as an essential component of therapy in patients with presumed RH. Conversely, we propose that RH should be diagnosed only in patients whose BP values show to be resistant to an up-titrated dose of these drugs.

A literature review on cardiovascular risk in human immunodeficiency virus-infected patients: implications for clinical management

IntroductionIn recent years, there has been growing concern about an increasing rate of cardiovascular diseases in human immunodeficiency virus-infected patients, which could be associated with side effects of highly active antiretroviral therapy. It is likely that the metabolic disorders related to anti-human immunodeficiency virus treatment will eventually translate into a increased cardiovascular risk in patients submitted to such regimens. ObjectiveTo evaluate if human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy are at higher risk of cardiovascular diseases than human immunodeficiency virus infected patients not receiving highly active antiretroviral therapy, or the general population. Research design and methodsWe conducted a computer-based search in representative databases, and also performed manual tracking of citations in selected articles. ResultThe available evidence suggests an excess risk of cardiovascular events in human immunodeficiency virus-infected persons compared to non-human immunodeficiency virus infected individuals. The use of highly active antiretroviral therapy is associated with increased levels of total cholesterol, triglycerides, low-density lipoprotein and morphological signs of cardiovascular diseases. Some evidence suggested that human immunodeficiency virus-infected individuals on highly active antiretroviral therapy regimens are at increased risk of dyslipidemia, ischemic heart disease, and myocardial infarction, particularly if the highly active antiretroviral therapy regimen contains a protease inhibitor. ConclusionPhysicians must weigh the cardiovascular risk against potential benefits when prescribing highly active antiretroviral therapy. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving highly active antiretroviral therapy regimens, particularly for those with known underlying cardiovascular risk factors. A better understanding of the molecular mechanisms responsible for increased risk of cardiovascular diseases in human immunodeficiency virus-infected patients will lead to the discovery of new drugs that will reduce cardiovascular risk in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy.

Incidence of and Risk Factors for Adverse Cardiovascular Events Among Patients With Systemic Lupus Erythematosus

Patients with systemic lupus erythematosus (SLE) are at excess risk of cardiovascular events (CVEs). There is uncertainty regarding the relative importance of SLE disease activity, medications, or traditional risk factors in this increased risk. To gain insight into this, the authors analyzed data from a cohort of 1,874 patients with SLE who were seen quarterly at a single clinical center (April 1987-June 2010) using pooled logistic regression analysis. In 9,485 person-years of follow-up, the authors observed 134 CVEs (rate = 14.1/1,000 person-years). This was 2.66 times what would be expected in the general population based on Framingham risk scores (95% confidence interval: 2.16, 3.16). After adjustment for age, CVE rates were not associated with duration of SLE. However, they were associated with average past levels of SLE disease activity and recent levels of circulating anti-double-stranded DNA. Past use of corticosteroids (in the absence of current use) was not associated with CVE rates. However, persons currently using 20 mg/day or more of corticosteroids had a substantial increase in risk even after adjustment for disease activity. Thus, consistent with findings in several recent publications among cohorts with other diseases, current use of corticosteroids was associated with an increased risk of CVEs. These results suggest a short-term impact of corticosteroids on CVE risk.

Potential role of differential medication use in explaining excess risk of cardiovascular events and death associated with chronic kidney disease: A cohort study

BackgroundPatients with chronic kidney disease (CKD) are less likely to receive cardiovascular medications. It is unclear whether differential cardiovascular drug use explains, in part, the excess risk of cardiovascular events and death in patients with CKD and coronary heart disease (CHD).MethodsThe ADVANCE Study enrolled patients with new onset CHD (2001-2003) who did (N = 159) or did not have (N = 1088) CKD at entry. The MDRD equation was used to estimate glomerular filtration rate (eGFR) using calibrated serum creatinine measurements. Patient characteristics, medication use, cardiovascular events and death were ascertained from self-report and health plan electronic databases through December 2008.ResultsPost-CHD event ACE inhibitor use was lower (medication possession ratio 0.50 vs. 0.58, P = 0.03) and calcium channel blocker use higher (0.47 vs. 0.38, P = 0.06) in CKD vs. non-CKD patients, respectively. Incidence of cardiovascular events and death was higher in CKD vs. non-CKD patients (13.9 vs. 11.5 per 100 person-years, P < 0.001, respectively). After adjustment for patient characteristics, the rate of cardiovascular events and death was increased for eGFR 45-59 ml/min/1.73 m2 (hazard ratio [HR] 1.47, 95% CI: 1.10 to 2.02) and eGFR < 45 ml/min/1.73 m2 (HR 1.58, 95% CI: 1.00 to 2.50). After further adjustment for statins, β-blocker, calcium channel blocker, ACE inhibitor/ARB use, the association was no longer significant for eGFR 45-59 ml/min/1.73 m2 (HR 0.82, 95% CI: 0.25 to 2.66) or for eGFR < 45 ml/min/1.73 m2 (HR 1.19, 95% CI: 0.25 to 5.58).ConclusionsIn adults with CHD, differential use of cardiovascular medications may contribute to the higher risk of cardiovascular events and death in patients with CKD.

Cardiovascular Outcomes in Framingham Participants With Diabetes

We designed this study to explore to what extent the excess risk of cardiovascular events in diabetic individuals is attributable to hypertension. We retrospectively analyzed prospectively collected data from the Framingham original and offspring cohorts. Of the 1145 Framingham subjects newly diagnosed with diabetes mellitus who did not have a previous history of cardiovascular events, 663 (58%) had hypertension at the time that diabetes mellitus was diagnosed. During 4154 person-years of follow-up, 125 died, and 204 experienced a cardiovascular event. Framingham participants with hypertension at the time of diabetes mellitus diagnosis exhibited higher rates of all-cause mortality (32 versus 20 per 1000 person-years; P<0.001) and cardiovascular events (52 versus 31 per 1000 person-years; P<0.001) compared with normotensive subjects with diabetes mellitus. After adjustment for demographic and clinical covariates, hypertension was associated with a 72% increase in the risk of all-cause death and a 57% increase in the risk of any cardiovascular event in individuals with diabetes mellitus. The population-attributable risk from hypertension in individuals with diabetes mellitus was 30% for all-cause death and 25% for any cardiovascular event (increasing to 44% and 41%, respectively, if the 110 normotensive subjects who developed hypertension during follow-up were excluded from the analysis). In comparison, after adjustment for concurrent hypertension, the population-attributable risk from diabetes mellitus in Framingham subjects was 7% for all-cause mortality and 9% for any cardiovascular disease event. Although diabetes mellitus is associated with increased risks of death and cardiovascular events in Framingham subjects, much of this excess risk is attributable to coexistent hypertension.

The role of conventional and novel mechanisms in explaining increased risk of cardiovascular events in offspring with positive parental history

Parental history is a widely accepted risk factor for offspring cardiovascular events, although the mechanisms remain unclear. We examined the contribution of conventional and novel risk factors in explaining the excess risk of cardiovascular events in offspring with positive parental history (PH+). We collected conventional (blood pressure, cholesterol, adiposity), lifestyle, and novel (C-reactive protein, CRP) risk factors at baseline in participants from the Scottish Health Surveys (n = 5946, 44.5% men, aged 53.6 +/- 12.4 years), who were followed up over an average of 7.1 years for cardiovascular disease (CVD) events (a composite of fatal and nonfatal events incorporating acute myocardial infarction, coronary artery bypass surgery, percutaneous coronary angioplasty, stroke, heart failure). Younger PH+ participants (<65 years) were at higher risk of incident CVD events [age-adjusted and sex-adjusted hazard ratio = 1.91, 95% confidence interval (CI) 1.21-3.00] compared with PH-. Despite an association of PH+ with blood pressure, total and high-density lipoprotein cholesterol, CRP, and physical activity, less than 15% of the excess risk was explained through conventional and novel risk factors. However, the greatest risk of CVD was observed in PH+ participants with elevated CRP (> or =3 mg/l) (hazard ratio = 2.99, 95% CI 2.15-4.16) or hypertension (hazard ratio = 2.87, 95% CI 2.07-3.99). Only a small amount of the excess CVD risk associated with PH+ is accounted for by conventional and novel mechanisms. However, the combination of elevated CRP or hypertension with PH+ substantially increases the risk of CVD.