Renin-angiotensin-aldosterone System Antagonists Research Articles

Taboo in cardiology: renin-angiotensin-aldosterone system antagonists worsening renal failure.

The renin-angiotensin-aldosterone system (RAAS) allows normal kidneys to maintain a stable function in every situation of daily life but also intervenes to help when critical situations occur that reduce the filtrate. A typical example is heart failure with reduced ejection function (HFrEF) which inexorably becomes complicated over time with renal failure in what is now commonly defined as cardiorenal syndrome. Renin-angiotensin-aldosterone system antagonists have long been irreplaceable in the treatment of HFrEF due to their beneficial haemodynamic and prognostic effects. However, their use often leads to an acute reduction in the filtrate which often scares the clinician and sometimes leads them to suspend their use. In reality, no guideline has ever clearly indicated when a decline in renal function in a patient taking RAAS antagonists should be acceptable and not lead us to fear the associated acute kidney injury. Usually the nephrologist, called for advice, recommends reducing or suspending the RAAS antagonists, knowing that this will improve the filtration and reassure everyone. But is this the right solution? Are we certain that this choice leads to a better prognosis? This article will try to give a reasonable answer to one of the most frequent doubts that arise in our daily practice.

Ten year evolution of clinical characteristics and short-term outcome of patients admitted with heart failure

Abstract Background/Introduction Heart failure (HF) continues to be a leading cause of morbidity, decreased quality of life (QoL) and mortality worldwide. Contributing to decreased QoL is the high rehospitalization rate, which is often related to non-cardiac causes, highlighting the important multimorbidity of the HF population. Detailed clinical and outcome data for HF admissions in Belgium over time are only scarcely available. Purpose We aimed to evaluate and compare two groups of patients admitted with HF ten years apart, regarding clinical characteristics, comorbidities, use of HF medication and devices, as well as rehospitalization rate and all-cause mortality three months post-discharge. Methods This is a monocentric retrospective observational cohort study conducted in Belgium. Two groups of patients admitted for acute decompensated HF who were discharged alive were included and compared: 340 patients during 2011-2012 and 319 patients during 2021-2022. Results The two cohorts did not differ significantly regarding age (77.3 vs. 78.4 years), gender (47.4 vs. 44.5% women), number of patients with HF with reduced ejection fraction (47.4 vs. 48.6%) and NT-proBNP on admission (8514 vs. 7398 pg/mL). Similarly, comorbidities including diabetes, chronic obstructive pulmonary disease, peripheral artery disease, stroke and renal failure were comparable in both groups. Concerning medical therapy at discharge, mineralocorticoid receptor antagonists (MRA) were used significantly more frequently in the latest cohort. However, there was no change in administration of beta-blockers or renin angiotensin aldosterone system antagonists. As part of the implementation of new therapies for heart failure with reduced ejection fraction, 29% of patients were prescribed sodium-glucose cotransporter-2 (SGLT-2) inhibitors, while sacubitril/valsartan was given in 13% of the cases. The use of internal defibrillators (ICD) and resynchronization devices (CRT) doubled from 2011-2012 to 2021-2022 (3.9 vs. 9.6%, p = 0.002). In-hospital length of stay decreased significantly over a ten-year period across all ejection fraction subgroups from 7 to 5 days (figure 1). The combined outcome of rehospitalization for HF and all-cause mortality three months post-discharge remained constant at approximately 20% (figure 2). Conclusion Clinical characteristics and comorbidities of patients admitted with acute decompensated HF did not change significantly between 2011 and 2022. Uptake of evidence-based medicine for HF increased, especially for MRA, SGLT-2 inhibitors and sacubitril/valsartan, as did the use of ICD and CRT, but still with considerable potential for improvement. Although in-hospital length of stay decreased significantly over time, rehospitalization rates for HF and all-cause mortality within 90 days post-discharge remained high and did not improve. These sobering results illustrate the need for continuing efforts to improve the care and outcome of HF patients.

Modern possibilities of correction of broncho-obstructive syndrome in chronic heart failure of ischemic origin in combination with chronic obstructive pulmonary disease: simple randomized parallel group study

AIM: To evaluate the efficacy and safety of complex basic therapy for chronic heart failure (CHF) of ischemic origin in combination with chronic obstructive pulmonary disease (COPD) with the inclusion of prolonged bronchodilators.
 MATERIALS AND METHODS: The study included 67 patients (50 men and 17 women) with CHF IIIII functional class (FC) with left ventricular ejection fraction (LVEF) of 45% in combination with moderate-to-severe COPD (GOLD). The patients were divided into three groups: group 1 (n=30) received formoterol as part of therapy, group 2 (n=19) received aclidinium, and group 3 (n=18) received a fixed combination of aclidinum and formoterol. The basic therapy for CHF included nebivolol, losartan, eplerenone, diuretics, low-dose glucocorticosteroids, nitrates, and cardiac glycosides (if necessary). The clinical condition of patients, intracardiac hemodynamics, was indicated using echocardiography, a 6-min walking test (6MWT), bifunctional 24-h monitoring of blood pressure and heart rate, and spirometry. Quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire, St. Georges Respiratory Questionnaire, and Modified Medical Research Council dyspnea scale.
 RESULTS: After 6 months of therapy, the clinical and instrumental parameters and quality of life improved in all groups. At the end of the observation period, the average FC of CHF and dyspnea severity decreased by 17.5, 18.2, 20.1 20.5, 24.2, and 28.1%, respectively. The increase in exercise tolerance was 22.1, 22.6, and 29.2%. An improvement in intracardiac hemodynamics was noted. The LVEF increased by 17.1, 20.5, and 24.6%, and the myocardial mass index decreased by 8.7, 14.2, and 17.4%. The total peripheral vascular resistance, degree of pulmonary hypertension, and duration and frequency of painless myocardial ischemia significantly decreased. The best results were obtained in group 3 using nebivolol, reninangiotensinaldosterone system antagonists, and a combination of long-acting bronchodilators. Therapy was well tolerated by all study groups, with no serious adverse side effects.
 CONCLUSION: The inclusion of nebivolol and losartan in basic therapy, while taking long-acting bronchodilators, improves the clinical and functional states of patients and quality of life, and slows down disease progression. When used in a fixed combination, the use of aclidinium and formoterol improves spirometry to a greater extent.

Atrial fibrillation in heart failure patients: An update on renin-angiotensin-aldosterone system pathway blockade as a therapeutic and prevention target.

Heart failure (HF) and atrial fibrillation (AF) are two cardiovascular (CV) entities that affect millions of individuals worldwide and their prevalence is translated into a significant impact on health care systems. The common pathophysiological pathways that these two share have created an important clinical interrelation, as the coexistence of HF and AF is associated with worse prognosis and treatment challenges. Renin-angiotensin-aldosterone system (RAAS), a critical mechanism in blood pressure (BP) control, was proved to be involved in the pathogenesis of both conditions contributing to their further coexistence. Successful control of BP is of great importance to the management of HF, crucial for the prevention of arrhythmiogenic substrates, while RAAS antagonists may possibly affect the development of new-onset AF as well. There are numerous studies that evaluated the effectiveness of RAAS blockade in AF/HF population and despite comparable or modest results, there is a well-established suggestion that RAAS blockers may contribute to a reduction of HF, CV events and recurrence of AF, along with their potential effective role in the new-onset AF prophylaxis. Angiotensin receptor blockers, according to the evidence, are more effective in that direction, followed by angiotensin converting enzyme inhibitors, whereas the data on aldosterone antagonists are not encouraging, yet do have the potential of significant CV disease modificators regardless of their effects on BP.

The role of renin-angiotensin system in patients with left ventricular assist devices.

End-stage heart failure is a condition in which the up-regulation of the systemic and local renin-angiotensin-aldosterone system (RAAS) leads to end-organ damage and is largely irreversible despite optimal medication. Left ventricular assist devices (LVADs) can downregulate RAAS activation by unloading the left ventricle and increasing the cardiac output translating into a better end-organ perfusion improving survival. However, the absence of pulsatility brought about by continuous-flow devices may variably trigger RAAS activation depending on left ventricular (LV) intrinsic contractility, the design and speed of the pump device. Moreover, the concept of myocardial recovery is being tested in clinical trials and in this setting LVAD support combined with intense RAAS inhibition can promote recovery and ensure maintenance of LV function after explantation. Blood pressure control on LVAD recipients is key to avoiding complications as gastrointestinal bleeding, pump thrombosis and stroke. Furthermore, emerging data highlight the role of RAAS antagonists as prevention of arteriovenous malformations that lead to gastrointestinal bleeds. Future studies should focus on the role of angiotensin receptor inhibitors in preventing myocardial fibrosis in patients with LVADs and examine in greater details the target blood pressure for these patients.

SARS-CoV-2 Infections: An ACE in the Hole and Systems Biology Studies—a Research Agenda

SARS-CoV-2 Infections: An ACE in the Hole and Systems Biology Studies—a Research Agenda

Coronavirus Disease 2019 (COVID-19): Do Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Have a Biphasic Effect?

Coronavirus Disease 2019 (COVID-19): Do Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Have a Biphasic Effect?

Meta-Analysis Evaluating the Effects of Renin-Angiotensin-Aldosterone System Blockade on Outcomes of Heart Failure With Preserved Ejection Fraction

Clinical trials of renin-angiotensin-aldosterone system (RAAS) antagonists in heart failure with preserved ejection fraction (HFpEF) have suggested neutral results and treatment is focused on associated symptoms and comorbidities. MEDLINE and EMBASE were searched through October 2019 for randomized controlled studies investigating the effects of different RAAS antagonists in patients with HFpEF. The main outcomes were all-cause mortality, trial defined cardiovascular mortality, and heart failure (HF) hospitalizations. To compare different RAAS antagonists, a random-effects restricted-maximum-likelihood network meta-analysis based on a frequentist framework for indirect and mixed comparisons was used. We used p scores to rank best treatments per outcome. Our search identified 5 eligible clinical trials (PEP-CHF, perindopril; CHARM-preserved, candesartan; I-PRESERVE, irbesartan; TOPCAT, spironolactone; PARAGON-HF, sacubitril-valsartan and valsartan) enrolling a total 10,523 on RAAS antagonists and 6,259 controls. We did not identify any statistical difference in all-cause and cardiovascular mortality among RAAS antagonists and placebo. The combination of sacubitril-valsartan was associated with significantly decreased HF hospitalization risk compared with controls (odds ratio 0.73, 95% confidence interval 0.61 to 0.87) and angiotensin II receptor blockers (odds ratio 0.80, 95% confidence interval 0.71 to 0.91), without heterogeneity among studies (I2 = 0). Angiotensin receptor neprilysin inhibitor (ARNI) ranked better than other RAAS antagonists for HF hospitalizations (p value 0.9). In conclusion, RAAS antagonists do not affect mortality but the combination of sacubitril-valsartan is associated with lower HF hospitalizations in HFpEF patients.

Renin-angiotensin-aldosterone system antagonists: perioperative management.

Renin-angiotensin-aldosterone system antagonists: perioperative management.

Consequences of continuing renin angiotensin aldosterone system antagonists in the preoperative period: a systematic review and meta-analysis

BackgroundPatients who use angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) are prone to developing side effects like hypotension and even refractory hypotension during anesthesia use, and whether ACEIs/ARBs should be continued or discontinued in such patients remains debatable. The present systematic review and meta-analysis was conducted to clarify the consequences of continuing or withholding these drugs, especially with regards to the incidence of intraoperative hypotension, in patients who continue to use ACEIs/ARBs on the day of their scheduled surgery.MethodsStudies with data pertinent to the incidence of intraoperative hypotension during anesthesia use in patients who continued the use of ACEIs/ARBs on the day of their scheduled surgery were considered for inclusion.ResultsThirteen studies reporting on the incidences of intraoperative hypotension between patients who continued receiving ACEIs/ARBs and those who did not on the day of their surgical procedure were included. The pooled effects showed that hypotension during anesthesia was more likely to develop in patients who continued to take ACEIs/ARBs when compared to those who did not (RR = 1.41, 95% CI: 1.21–1.64). However, there were no significant differences between these groups of patients with regards to postoperative complications including ST-T abnormalities, myocardial injury, myocardial infarction, stroke, major adverse cardiac events, acute kidney injury, or death (RR = 1.25, 95% CI: 0.76–2.04). The differences remained similar in subgroup analyses and sensitivity analyses.ConclusionsNo sufficient available evidence to recommend discontinuing ACEIs/ARBs on the day of surgery was found in this literature review and meta-analysis. However, anesthetists should be cautious about the risk for intraoperative hypotension in patients chronically receiving ACEIs/ARBs, and should know how to treat it effectively.

Treatment of Hyperkalemia in Heart Failure.

The aim of this paper is to discuss strategies for prevention and management of hyperkalemia in patients with heart failure, including the role of novel therapies. Renin-angiotensin-aldosterone system (RAAS) antagonists, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and mineralocorticoid receptor antagonists (MRA) decrease mortality and morbidity in heart failure but increase the risk of hyperkalemia, especially when used in combination. Prevention of hyperkalemia and its associated complications requires careful patient selection, counseling regarding dietary potassium intake, awareness of drug interactions, and regular laboratory surveillance. Recent data suggests that the risk of hyperkalemia may be further moderated through the use of combined angiotensin-neprilysin inhibitors, novel MRAs, and novel potassium binding agents. Clinicians should be mindful of the risk of hyperkalemia when prescribing RAAS inhibitors to patients with heart failure. In patients at highest risk, such as those with diabetes, the elderly, and advanced chronic kidney disease, more intensive laboratory surveillance of potassium and creatinine may be required. Novel therapies hold promise for reducing the risk of hyperkalemia and enhancing the tolerability of RAAS antagonists.

Is the Currently Used Prescription Adjudication Date a Good Proxy for Calculating Medication Refill Adherence?

The Centers for Medicare & Medicaid Services (CMS) adopted the proportion of days covered (PDC) calculation for use in their Five-Star Quality Rating System for Medicare Advantage and Prescription Drug Plans. This calculation uses the prescription adjudication date (i.e., date the prescription is billed to the benefits manager by a pharmacy) as a proxy for medication adherence. Adherence programs, such as automatic refill programs, have become commonplace in community pharmacy and have been identified by industry leaders as interfering with the ability to accurately measure adherence using PDC. To evaluate the prescription pickup date instead of the currently used adjudication date to calculate PDC in the presence of a community pharmacy automatic refill program. This study used a post-only quasi-experimental design with patients aged 65 years or older enrolled in automatic and manual refill programs in a 29-store community pharmacy chain during 2014. PDC was calculated using the prescription adjudication date and pickup date (i.e., date the patient brought the medication home) using pharmacy dispensing data for CMS adherence metrics medications, including statins, renin angiotensin aldosterone system antagonists (RASA), and noninsulin diabetes medications. Mann-Whitney U and effect size calculations evaluated differences in PDC between automatic and manual refill prescriptions for the adjudication date and pickup date, as well as the difference in PDC between adjudication and pickup date. 10,936 prescriptions were included with 21.9% enrolled in the automatic refill program. Mean (SD) adherence was 88.6 (17.6) and 86.4 (17.1) for automatic refills and 85.8 (19.0) and 85.0 (18.9) for manual refills, using the adjudication date and pickup date PDC, respectively. Significant difference existed between automatic and manual refill prescriptions using the adjudication date (P < 0.001) but not for the pickup date. The difference between adjudication and pickup date PDC ranged from 0% to 32.0% for automatic refills and 0% to 38.7% for manual refills. The difference between adjudication and pickup date PDC was significant when comparing automatic and manual refill prescriptions (P < 0.001). The artificial inflation seen with adjudication date PDC indicates that the prescription pickup date is a more accurate reflection of patient medication taking. Automatic refills resulted in a less reliable PDC compared with manual refill prescriptions. Discussion about the continued use of the adjudication date to calculate PDC is needed. The project described was supported by the Clinical and Translational Science Award (CTSA) program through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Lester is employed as a pharmacist in the pharmacy chain that participated in this study. The authors report no other relevant conflict of interest. Study concept and design were contributed primarily by Lester, along with Look and Chui. Lester took the lead in data collection, along with Look, and data interpretation, along with Look and Chui. The manuscript was written and revised primarily by Lester, along with Look and Chui.

The Influence of a Community Pharmacy Automatic Prescription Refill Program on Medicare Part D Adherence Metrics.

The Centers for Medicare & Medicaid Services (CMS) include measures of medication adherence within its Medicare Part D star ratings program. These adherence measures have motivated the development of new methods to improve patient adherence. Automatic prescription refill programs in community pharmacies are an intervention that has seen widespread adoption in recent years. These automatic refill programs anticipate and initiate prescription refills on a standardized, recurrent basis. As a result, prescription refills may be filled before a patient typically might initiate a refill. This study measures the effect of an automatic prescription refill program on 3 adherence metrics used by CMS within Medicare Part D star ratings. To compare the value of Medicare Part D adherence metrics for an automatic prescription refill program relative to standard prescription refills. Prescription dispensing data (January 1, 2014-December 31, 2014) from a chain of 29 pharmacies in a midwestern state were used to conduct this analysis. A post-only, quasi-experimental design separated patients into automatic and standard prescription refill cohorts. Refill adherence was calculated using proportion of days covered (PDC) for each of the 3 adherence metrics used by CMS for statins, renin angiotensin aldosterone system antagonists (RASA), and noninsulin diabetes medications. The adherence rate was defined as the proportion of patients with a PDC ± 80%. Inclusion criteria for patients followed the Pharmacy Quality Alliance technical specifications. Chi-square analysis and multiple logistic regression were used to examine differences in PDC > 80% between the 2 study cohorts. There were 1,018, 1,006, and 368 patients for the automatic refill cohort and 3,928, 3,409, and 1,207 patients for the standard refill cohort in the statin, RASA, and diabetes adherence metrics, respectively. The mean age [SD] of patients was between 79.2 [±8.5] and 80.8 [±9.9] years across all cohorts. Patients in the automatic prescription refill program tended to take less than 1 additional chronic medication compared with the standard refill prescription cohort. The proportion of adherent patients ranged from 73.6% to 76.4% for standard refill cohorts and 77.5% to 83.6% for automatic refill cohorts. Differences between study cohorts were statistically significant for all the adherence metrics based on the chi-square test (P < 0.05). Patients enrolled in the automatic prescription refill program were more likely to be adherent to the statin (OR = 1.51, 95% CI = 1.26-1.82), RASA (OR = 1.20, 95% CI = 1.01-1.42), and diabetes (OR = 1.44, 95% CI = 1.06-1.96) metrics. Patients enrolled in the automatic prescription refill program were more likely to be adherent to their medications. Enrollment in automatic prescription refill programs could be encouraged by health plans and pharmacists because of their potential effect on Medicare Part D star ratings. The project described was supported by the Clinical and Translational Science Award (CTSA) program through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Lester is employed as a pharmacist in the participating pharmacy chain. The authors report no other relevant conflict of interest. Study concept and design were primarily contributed by Lester, with assistance from the other authors. Lester took the lead in data collection, along with Chui, and data interpretation was performed by Lester, Mott, and Chui. The manuscript was written primarily by Lester, along with Mott, and revised by Lester, Mott, and Chui.

Calibrating the impact of dual RAAS blockade on the heart and the kidney - balancing risks and benefits.

Overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in the pathophysiology of heart failure (HF) and chronic kidney disease (CKD). RAAS antagonists can significantly improve clinical outcomes, but monotherapy blocks but one step of the RAAS and can be bypassed through compensatory mechanisms. Providing more complete RAAS blockade by deploying drugs with complementary actions seemed logical - hence the practice of using dual (or triple) RAAS inhibitors. However, RAAS antagonists also exhibit dose-limiting side effects, including acute kidney injury, hyperkalaemia and hypotension, which blunt their overall effectiveness. Despite achieving better RAAS blockade, several trials failed to show clinical outcome improvements. Patients with concomitant CKD and HF (cardiorenal syndrome) are at the greatest risk of these adverse events and therefore the least able to benefit, yet they also have the worst prognosis. This paradox, where those most in need have fewest therapeutic options, poses three questions which are the focus of this review: whether (i) novel therapies that prevent adverse effects can restore therapeutic benefits to patients who would otherwise be RAAS-therapy intolerant, (ii) there are any validated alternatives to their use and (iii) newer approaches to the detection of fluid congestion are ready for implementation.

Antihypertensive drugs

Antihypertensive drugs

Fasting during the month of Ramadan among patients with chronic kidney disease: renal and cardiovascular outcomes.

BackgroundFasting during the month of Ramadan is a religious obligation for Muslims who represent 20% of the world population. This study explores the safety of fasting for a whole month among patients with chronic kidney disease (CKD) with the possible risk of dehydration and hyperviscosity leading to deterioration of kidney functions and vascular thrombosis.MethodsWe followed CKD patients with stable kidney function who chose to fast during the month of Ramadan. A group of nonfasting CKD patients served as controls. Serum creatinine was recorded at the beginning of the month, after 1 week of fasting, at the end of the month and 3 months later. Patients were followed for major adverse cardiovascular events (MACE).ResultsA total of 131 CKD patients were recruited and included in two groups: fasting and nonfasting (mean baseline estimated glomerular filtration rate 27.7, SD 13 and 21.5, SD 11.8 mL/min/1.73 m2, respectively). A rise of serum creatinine was noted during fasting in 60.4% of patients by Day 7 and was associated with intake of renin angiotensin aldosterone system antagonists [relative risk (RR) 2, P = 0.002]. Adverse cardiovascular events were observed in six patients in the fasting cohort and were associated with a rise of serum creatinine after 1 week of fasting (P = 0.009) and the presence of pre-existing cardiovascular disease (RR 15, P = 0.001); the latter association was confirmed by logistic regression analysis. Only one event was recorded in the nonfasting group, P = 0.036.ConclusionsMACE occurred more frequently among fasting CKD patients with pre-existing cardiovascular disease and were predicted by an early rise of serum creatinine.

Biomarkers in acutely decompensated heart failure with preserved or reduced ejection fraction

Acute decompensated heart failure (ADHF) occurs with preserved (heart failure with preserved ejection fraction [HFpEF] ≥50%) or reduced (heart failure with reduced ejection fraction [HFrEF] <50%) ejection fraction. Natriuretic peptide (NP) levels are lower in HFpEF than HFrEF. We hypothesized that lower NP levels in HFpEF may be associated with other differences in biomarkers, specifically, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, and a biomarker that reflects collagen synthesis. In this prespecified ancillary analysis of patients with ADHF enrolled in the Diuretic Optimization Strategies Evaluation study, clinical features and N-terminal pro-B-type NP, cystatin C, plasma renin activity, aldosterone, oxidative stress (uric acid), and procollagen type III N-terminal peptide were compared in HFpEF and HFrEF at enrollment and 60-day follow-up. Compared with HFrEF (n = 219), HFpEF (n = 81) patients were older, heavier, more commonly female, less treated with RAAS antagonists, but with similar New York Heart Association class, jugular venous pressure, and edema severity. N-terminal pro-B-type NP was lower, and systolic blood pressure and cystatin C were higher in HFpEF. Despite higher systolic blood pressure and less RAAS antagonist use in HFpEF, plasma renin activity and aldosterone levels were similar in HFpEF and HFrEF as were uric acid and procollagen type III N-terminal peptide levels. Changes in biomarker levels from enrollment to 60 days were similar between HFrEF (n = 149) and HFpEF (n = 50). Lower NP levels in decompensated HFpEF occur in association with similar ADHF severity, more impaired vascular and renal function but similar elevation of biomarkers that reflect RAAS activation, oxidative stress, and collagen synthesis as in HFrEF.

The association of retinopathy and low GFR in type 2 diabetes

AimsWe sought to determine characteristics which strengthen the association between markers of diabetic kidney disease and retinopathy. MethodsMultivariate regression analyses of NHANES 2005–2008 assessed the association of retinopathy with renal insufficiency and albuminuria. Analyses were stratified to evaluate ethnicity/race, obesity, and use of renin–angiotensin–aldosterone system antagonists as effect modifiers of this relationship. ResultsOf 269 participants with renal insufficiency, 35% had no microalbuminuria and no retinopathy; 16.1% had retinopathy with no microalbuminuria; 27.1% had microalbuminuria and no retinopathy and 22% had both microalbuminuria and retinopathy. Stratified, multivariate logistic regression analyses demonstrated retinopathy to be significantly predictive of renal insufficiency only in nonHispanic Blacks (OR=2.7; 95% CI 1.2, 6.1), obesity (OR=2.6; 95% CI 1.3, 5.5) and in those participants not using renin–angiotensin–aldosterone blockers (OR=2.5; 95% CI 1.1, 5.7). Analyses showed an independent relationship between retinopathy and albuminuria only when albuminuria was modeled continuously. ConclusionsIn older onset diabetes, the absence of albuminuria and retinopathy is common among individuals with renal insufficiency. The relationship between microvascular complications of the eye and kidney may vary according to ethnicity, obesity and use of renin–angiotensin–aldosterone antagonists. These findings need to be confirmed in other large, diverse cohorts.

Clinical Considerations of Heritable Factors in Common Heart Failure

Heart failure is a common condition responsible for at least 290 000 deaths each year in the United States alone.1 A small minority of heart failure cases are attributed to Mendelian or familial cardiomyopathies. The majority of systolic heart failure cases are not familial but represent the end result of 1 or many conditions that primarily injure the myocardium sufficiently to diminish cardiac output in the absence of compensatory mechanisms. Paradoxically, because they also injure the myocardium, it is the chronic actions of the compensatory mechanisms that in many instances contribute to the progression from simple cardiac injury to dilated cardiomyopathy and overt heart failure. Thus, the epidemiology of common heart failure appears to be just as sporadic as its major antecedent conditions (atherosclerosis, diabetes, hypertension, and viral myocarditis). Familial trends in preclinical cardiac remodeling2 and risk of developing heart failure3 reveal an important role for genetic modifiers in addition to clinical and environmental factors. Candidate gene studies performed over the past 10 years have identified a few polymorphic gene variants that modify risk or progression of common heart failure.4 Whole-genome sequencing will lead to the discovery of other genetic modifiers that were not candidates.5 The imminent availability of individual whole-genome sequences at a cost competitive with available genetic tests for familial cardiomyopathy will no doubt further expand the list of putative genetic heart failure modifiers. Heart failure risk alleles along with traditional clinical factors will need to be considered by clinical cardiologists in their design of optimal disease surveillance and prevention programs and in individually tailoring heart failure management. The use of individual genetic make-up is likely to have the earliest and greatest impact on managing patients with heart failure by tailoring available pharmacotherapeutics to optimize patient response and minimize adverse effects (ie, the …

Anti-hypertensive drugs and left ventricular hypertrophy: a clinical update

Structural remodelling of the heart, known as left ventricular hypertrophy (LVH), is a consequence of systemic hypertension, and is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, particular attention should be paid to the identification, prevention and treatment of this condition in hypertensive patients. LVH seems to benefit from all classes of anti-hypertensive drugs; however, antagonists of the renin-angiotensin-aldosterone system (RAAS) have demonstrated an additional benefit in the inhibition and reversal of myocardial interstitial fibrosis. Nevertheless, in evaluating the degree of arterial hypertension and organ damage, many neuro-hormonal systems are involved, primarily the sympathetic nervous system, thereby explaining the use of different classes of anti-hypertensive drugs to prevent or reduce LVH. The RAAS antagonists are actually the recommended anti-hypertensive agents to prevent organ damage in hypertensive subjects or in hypertensives with evidence of LVH to reduce cardiovascular mortality and morbidity.