Retinopathy and Progression of CKD: The CRIC Study

Background and objectives

Retinal abnormalities may be associated with changes in the renal vasculature. This study assessed the association between retinopathy and progression of kidney disease in participants of the Chronic Renal Insufficiency Cohort (CRIC) study.

Design, setting, participants, & measurements

This was a prospective study in which patients with CKD enrolled in CRIC had nonmydriatic fundus photographs of both eyes. All CRIC participants in six clinical sites in which fundus cameras were deployed were offered participation. Photographs were reviewed at a reading center. The presence and severity of retinopathy and vessel calibers were assessed using standard protocols by graders masked to clinical information. The associations of retinal features with changes in eGFR and the need for RRT (ESRD) were assessed.

Results

Retinal images and renal progression outcomes were obtained from 1852 of the 2605 participants (71.1%) approached. During follow-up (median 2.3 years), 152 participants (8.2%) developed ESRD. Presence and severity of retinopathy at baseline were strongly associated with the risk of subsequent progression to ESRD and reductions in eGFR in unadjusted analyses. For example, participants with retinopathy were 4.4 times (95% confidence interval [95% CI], 3.12 to 6.31) more likely to develop ESRD than those without retinopathy (P<0.001). However, this association was not statistically significant after adjustment for initial eGFR and 24-hour proteinuria. Venular and arteriolar diameter calibers were not associated with ESRD or eGFR decline. The results showed a nonlinear relationship between mean ratio of arteriole/vein calibers and the risk of progression to ESRD; participants within the fourth arteriole/vein ratio quartile were 3.11 times (95% CI, 1.51 to 6.40) more likely to develop ESRD than those in the first quartile (P<0.001).

Conclusions

The presence and severity of retinopathy were not associated with ESRD and decline in eGFR after taking into account established risk factors.     

Left Ventricular Longitudinal Myocardial Function in Overt Hypothyroidism: A Tissue Doppler Echocardiographic Study

Background: The aim of this study was to assess left ventricular (LV) myocardial regional function in overt hypothyroidism by use of tissue Doppler imaging and to compare the results to the hormonal profile and standard Doppler echocardiographic examination. Methods: Hypothyroidic (Group 1, n = 25) and euthyroidic patients (Group 2, n = 25) underwent transthorasic echocardiography, strain and strain rate imaging. Results: Standard echocardiography showed that patients with overt hypothyroidism had significantly longer isovolumic contraction time (IVCT) (P < 0.05), deceleration time (DT) (P = 0.014) and isovolumic relaxation time (IVRT) (P = 0.022). Tissue Doppler imaging showed that the mean peak systolic strain (SI) (16.47 ± 1.45 vs. 20.63 ± 1.51, P < 0.001), the mean peak systolic strain rate (SSR) (1.05 ± 0.13 vs. 1.47 ± 0.11, P < 0.001), the mean peak early diastolic strain rate (ESr) (1.72 ± 0.38 vs. 2.03 ± 0.25, P < 0.05) and the mean peak late diastolic strain rate (ASr) (1.22 ± 0.31 vs. 1.46 ± 0.32, P < 0.05) were significantly lower in Group 1 compared to Group 2. For all patients, the systolic strain and systolic strain rate parameters negatively correlated with thyroid stimulating hormone levels and positively correlated with the levels of free triiodothyronine (fT₃) and free tetraiodothyronine (fT₄). Conclusion: These results indicate that overt hypothyroidism is associated with early impairment in LV longitudinal myocardial function, and that tissue Doppler echocardiography is useful for the grading of disease and detection of early impairment. (ECHOCARDIOGRAPHY 2010;27:505‐511)     

Study on Left Ventricular Diastolic Function under Different Left Ventricular Systolic Function

Ithasbecomeincreasinglyclearthatabnormali－tiesofdiastolicfunctionhaveamajorroleinproducingsignsandsymptomsinpatientspresentingwithhearfailure犤１，２犦．Asmanyasone－thirdofpatientswiththediagnosisofheartfailurehavenormalsystolicfunction，whichimplicates     

Risk Factors for CKD Progression: Overview of Findings from the CRIC Study

The Chronic Renal Insufficiency Cohort (CRIC) Study is an ongoing, multicenter, longitudinal study of nearly 5500 adults with CKD in the United States. Over the past 10 years, the CRIC Study has made significant contributions to the understanding of factors associated with CKD progression. This review summarizes findings from longitudinal studies evaluating risk factors associated with CKD progression in the CRIC Study, grouped into the following six thematic categories: (1) sociodemographic and economic (sex, race/ethnicity, and nephrology care); (2) behavioral (healthy lifestyle, diet, and sleep); (3) genetic (apoL1, genome-wide association study, and renin-angiotensin-aldosterone system pathway genes); (4) cardiovascular (atrial fibrillation, hypertension, and vascular stiffness); (5) metabolic (fibroblast growth factor 23 and urinary oxalate); and (6) novel factors (AKI and biomarkers of kidney injury). Additionally, we highlight areas where future research is needed, and opportunities for interdisciplinary collaboration.     

POINT: A Prescription to Decrease Left Ventricular Function

The Courage Trial, published in 2007, has significantly reduced the incidence of treating stable angina with angioplasty. The investigators randomized 2297 patients with documented cardiac ischemia to conservative or invasive therapy and concluded that there was no difference in major events during a follow-up of 2.5 to 7 years and that the urge to open the narrowed artery was unjustified. Over the years it has been well documented by myocardial biopsy that repeated ischemic episodes result in replacement of myocardial cells by fibrous tissue, loss of mitochondria, and deterioration of left ventricular function. Ischemic episodes often occur in the absence of angina so that it is impossible to determine whether the therapy is reducing the magnitude or duration of the process. Also, in their study, 32% of the conservatively treated patients crossed over to invasive. The evidence indicated that conservative treatment may result in a progressive decrease in left ventricular function.     

Relation of Serum Lipids and Lipoproteins with Progression of CKD: The CRIC Study

Background and objectives

Hyperlipidemia is common in patients with CKD. The objective of this study was to evaluate whether measures of plasma lipids and lipoproteins predict progression of kidney disease in patients with CKD.

Design, setting, participants, & measurements

Prospective cohort study in adults (n=3939) with CKD aged 21–74 years recruited between 2003 and 2008 and followed for a median of 4.1 years. At baseline, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), apoA-I , apoB, and lipoprotein(a) [Lp(a)] were measured. The outcomes were composite end point of ESRD or 50% decline in eGFR from baseline (rate of change of GFR).

Results

Mean age of the study population was 58.2 years, and the mean GFR was 44.9 ml/min per 1.73 m²; 48% of patients had diabetes. None of the lipid or lipoprotein measures was independently associated with risk of the composite end point or rate of change in GFR. However, there were significant (P=0.01) interactions by level of proteinuria. In participants with proteinuria<0.2 g/d, 1-SD higher LDL-C was associated with a 26% lower risk of the renal end point (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.59 to 0.92; P=0.01), and 1-SD higher total cholesterol was associated with a 23% lower risk of the renal end point (HR, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In participants with proteinuria>0.2 g/d, neither LDL-C (HR, 0.98; 95% CI, 0.98 to 1.05) nor total cholesterol levels were associated with renal outcomes. Treatment with statins was reported in 55% of patients and was differential across lipid categories.

Conclusions

In this large cohort of patients with CKD, total cholesterol, triglycerides, VLDL-C, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) were not independently associated with progression of kidney disease. There was an inverse relationship between LDL-C and total cholesterol levels and kidney disease outcomes in patients with low levels of proteinuria.     

Left Atrial Structure and Function,and Left Ventricular Diastolic Dysfunction: JACC State-of-the-Art Review

Defining left atrial (LA) function has recently emerged as a powerful parameter, particularly in evaluation of left ventricular (LV) diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction. Echocardiographic assessment of LVDD by echocardiography remains a challenging task; recent recommendations provide a simpler approach than previous. However, the shortcomings of the proposed approach (including transmitral flow, tissue velocity, maximum left atrial volume [LAV], and estimated pulmonary artery systolic pressure), lead to the presence and severity of LVDD remaining undetermined in a significant proportion of patients. Maximum LAV is a surrogate measure of the chronicity and severity of LVDD, but LAV alone is an insensitive biomarker of early phases of LVDD, because the LA may take time to remodel. Because the primary function of the LA is to modulate LV filling, it is not surprising that functional LA changes become evident at the earliest stages of LVDD. Moreover, LA function may provide additive value, not only in diagnosing LVDD, but also in grading its severity and in monitoring the effects of treatment. The current review provides a critical appraisal on the existing evidence for the role of LA metrics in evaluation of LVDD and consequent heart failure with preserved ejection fraction.     

Association of Left Ventricular Longitudinal and Circumferential Systolic Dysfunction With Diastolic Function in Hypertension: A Nonlinear Analysis Focused on the Interplay With Left Ventricular Geometry

BackgroundThe relationships of left ventricular (LV) longitudinal and circumferential systolic dysfunction with diastolic performance in hypertensive patients have never been compared.Methods and ResultsIn 532 asymptomatic hypertensive patients, circumferential function was assessed with the use of midwall fractional shortening (mFS) and stress-corrected mFS (SCmFS), whereas longitudinal function was assessed with the use of left atrioventricular plane displacement (AVPD) and systolic mitral annulus velocity (s′). Early diastolic annular velocity (e′) and the E/e′ ratio were measured. Global longitudinal and circumferential strain were determined in a subset of 210 patients. e′ was linearly related to all systolic indexes (AVPD: R = 0.40; s′: R = 0.39; mFS: R = 0.16; SCmFS: R = 0.17; all P < .0001), but the correlations were stronger with longitudinal indexes than with circumferential ones (P < .0001). E/e′ was nonlinearly related to AVPD (R = −0.49; P < .0001) and s′ (R = −0.34; P < .0001) and showed no relationship with mFS and SCmFS. Longitudinal indexes were superior to circumferential ones in predicting e′ <8 cm/s, E/e′ <8, and E/e′ ≥13. The effect of LV geometry on LV diastolic function was evident among patients with preserved systolic longitudinal function, but was blunted among patients with impaired longitudinal function. In multivariable analyses, only longitudinal indexes remained associated with e′ and E/e′. Analyses using strains provided similar results.ConclusionsIn asymptomatic hypertensive subjects, LV diastolic performance is independently associated with longitudinal systolic dysfunction, but not with circumferential systolic dysfunction. Subtle longitudinal systolic impairment plays a role in mediating the effect of LV geometry on diastolic performance. These findings may support the need of critically revising the concept of isolated diastolic dysfunction in these patients.     

Effect of Left Ventricular Function on Long-Term Left Ventricular Pacing and Sensing Threshold

Background: The effect of left ventricular (LV) systolic function on the long-term left ventricular pacing and sensing threshold is unclear. Methods and Results: We studied the effect of LV ejection fraction (LVEF) on the LV pacing and sensing threshold in 56 patients (mean age: 70.2 ± 10.5 years) underwent permanent LV pacing using a self-retaining coronary sinus lead (Model 1055 K, St Jude Medical, USA). In 49 patients, the LV lead was implanted for conventional pacemaker indication (sick sinus syndrome = 14, heart block = 26 or slow atrial fibrillation = 9). The remaining 7 patients were implanted for congestive heart failure. The LV pacing and sensing threshold, and lead impedance were compared between patients with LVEF <40% (Group 1, n = 28) and LVEF >40% (Group 2, n = 28) during implant and at 3-month follow up. The LV pacing lead was successfully implanted in all patients without any lead dislodgement on follow-up. At implant, Group 1 patients had a significant lower R wave amplitude, but similar LV pacing threshold and lead impedance as compared to Group 2. However, at 3-month follow-up, Group 1 patients had a significantly higher LV pacing threshold compared to Group 2 patients. There were no significant differences in the sensing threshold and lead impedance between the two groups. Furthermore, there was also a significant interval increase in LV pacing threshold in Group 1 patients (0.94 ± 0.12 V) after 3 months, but not in Group 2 patients (0.16 ± 0.08 V, p < 0.01). Conclusions: The results of this study suggest that the LV systolic function has a significant impact on the long-term LV pacing threshold. The long-term left ventricular pacing threshold in patients with left ventricular systolic dysfunction increased after implant and was higher than patients with normal left ventricular systolic function.     

Tissue Doppler to Assess Diastolic Left Ventricular Function

Doppler indices of left ventricular (LV) filling have been used traditionally for the assessment of LV diastolic function. In many circumstances, however, the interpretation of these indices is difficult because they respond to alterations of different physiological variables such as preload, relaxation, and heart rate. A typical example of their limitation is seen in patients with abnormal LV relaxation and increased preload compensation, who often present a "pseudonormal" LV filling pattern. Thus, there is a need for noninvasive indices of diastolic function capable of discriminating the effects of relaxation and preload. Tissue Doppler echocardiography (TDE) is available in most modern cardiac ultrasound imaging systems. TDE can be used to obtain regional myocardial velocities during isovolumic relaxation, early filling, and atrial systole with high spatial and temporal resolution. This article discusses the complementary role, limitations, and future challenges of TDE in the study of diastolic function.     

Ventricular Tachycardia in Patients with Impaired Left Ventricular Function: The Role of Propafenone

The combined occurrence of left ventricular dysfunction and -ventricular tachyarrhythmias portends a high annual mortality. Anti arrhythmic drugs can ameliorate ventricular arrhythmia and may reduce the risk of sudden cardiac death. We administered propafenone to 15 patients with ventricular tachyarrhythmias and left ventricular ejection fractions 40%. Propafenone significantly reduced isolated ventricular premature depolarizations, couplets, and ventricular tachycardia on ambulatory monitoring. Propafenone eliminated all exercise provocable ventricular tachycardia. Propafenone additionally abolished ventricular tachycardia inducible by programmed stimulation in 4 of 7 patients. In 8 patients studied before and during therapy, there was no significant change in left ventricular ejection fraction as determined by nuclear ventriculography. Propafenone was discontinued in 4 patients due to side effects. Seven patients receiving continuing propafenone therapy remain alive with only one patient suffering arrhythmia recurrence. Propafenone is an effective drug for the management of ventricular tachyarrhythmias and may be used for patients with impaired left ventricular function.