Background
Cardiac rehabilitation (CR) improves outcomes in heart disease yet remains vastly underutilized. Remote CR enhanced with a digital health intervention (DHI) may offer higher access and improved patient-centered outcomes over non-technology approaches. We sought to pragmatically determine whether offering a DHI improves CR access, cardiac risk profile, and patient-reported outcome measures.
Methods
Adults referred to CR at a tertiary VA medical center between October 2017 and December 2021 were offered enrollment into a DHI alongside other CR modalities using shared decision-making. The DHI consisted of remote CR with a structured, 3-month home exercise program enhanced with multi-component coaching, a commercial smartphone app, and wearable activity tracker. We measured completion rates among DHI participants and evaluated changes in 6-min walk distance, cardiovascular risk factors, and patient-reported outcomes from pre- to post-intervention.
Results
Among 1,643 patients referred to CR, 258 (16%) consented to the DHI where the mean age was 60 ± 9 years, 93% were male, and 48% were black. A majority (90%) of the DHI group completed the program. Over 3-months, significant improvements were seen in 6MWT (mean difference [MD] -29 m; 95% CI, 10 to 49; P < 0.01) and low-density lipoprotein cholesterol (MD -11 mg/dL; 95% CI, -17 to -5; P < 0.01), and the absolute proportion of patients who reported smoking decreased (10% vs 15%; MD, -5%; 95% CI, -8% to -2%; P < 0.01) among DHI participants with available data. No adverse events were reported.
Conclusions
The addition of a DHI-enhanced remote CR program was delivered in 16% of referred veterans and associated with improved CR access, markers of cardiovascular risk, and healthy behaviors in this real-world study. These findings support the continued implementation of DHIs for remote CR in real-world clinical settings.
RATIONALE: Low circulating progenitor cell numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis.
OBJECTIVES: To investigate whether low numbers of progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk.
METHODS AND RESULTS: Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD4+5 blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary end point of all-cause death.
There was an inverse association between CD34 and CD34/CD133 cell counts and risk of death in cohort 1 (β=-0.92, P=0.043 and β=-1.64, P=0.019, respectively) that was confirmed in cohort 2 (β=-1.25, P=0.020 and β=-1.81, P=0.015, respectively). Covariate-adjusted hazard ratios in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34/CD133 cell counts improved risk prediction metrics beyond standard risk factors.
CONCLUSIONS: Reduced circulating progenitor cell counts, identified primarily as CD34 mononuclear cells or its subset expressing CD133, are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction, and cell selection for cell-based therapies.
Objective: Stromal derived factor-1α/CXCL12 is a chemoattractant responsible for homing of progenitor cells to ischemic tissues. We aimed to investigate the association of plasma CXCL12 with long-term cardiovascular outcomes in patients with coronary artery disease (CAD).
Methods: 785 patients aged: 63±12 undergoing coronary angiography were independently enrolled into discovery (N=186) and replication (N=599) cohorts. Baseline levels of plasma CXCL12 were measured using Quantikine CXCL12 ELISA assay (R&D systems). Patients were followed for cardiovascular death and/or myocardial infarction (MI) for a mean of 2.6yrs. Cox proportional hazard was used to determine independent predictors of cardiovascular death/MI.
Results: The incidence of cardiovascular death/MI was 13% (N=99). High CXCL12 level based on best discriminatory threshold derived from the ROC analysis predicted risk of cardiovascular death/MI (HR=4.81, p=1×10-6) independent of traditional risk factors in the pooled cohort. Addition of CXCL12 to a baseline model was associated with a significant improvement in c-statistic (AUC: 0.67-0.73, p=0.03). Addition of CXCL12 was associated with correct risk reclassification of 40% of events and 10.5% of non-events. Similarly for the outcome of cardiovascular death, the addition of the CXCL12 to the baseline model was associated with correct reclassification of 20.7% of events and 9% of non-events. These results were replicated in two independent cohorts.
Conclusion: Plasma CXCL12 level is a strong independent predictor of adverse cardiovascular outcomes in patients with CAD and improves risk reclassification.
BACKGROUND—: Free radical scavengers have failed to improve patient outcomes promoting the concept that clinically important oxidative stress (OS) may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of non-free radical mediated oxidative stress with clinical outcomes.
METHODS AND RESULTS—: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7±2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (p<0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (=+1 SD & <-1 SD respectively) were associated with higher mortality (adjusted HR 1.63 (95% CI 1.19-2.21; HR 2.19 (95% CI 1.50-3.19), respectively) compared to those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR 1.92 (95% CI 1.39-2.64) and was independent of and additive to hs-CRP level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction.
CONCLUSIONS—: A high burden of OS, quantified by the plasma aminothiols, cystine, glutathione and their ratio is associated with mortality in patients with CAD, a finding that is independent of and additive to the inflammatory burden. Importantly, this data supports the emerging role of non-free radical biology in driving clinically important oxidative stress.
Objective. This paper illustrates the evolution of our knowledge of the arterial pulse from ancient times to the present. Several techniques for arterial pulse evaluation throughout history are discussed. Methods. Using databases including Worldcat, Pubmed, and Emory University Libraries' Catalogue, the significance of the arterial pulse is discussed in three historical eras of medicine: ancient, medieval, and modern. Summary. Techniques used over time to analyze arterial pulse and its characteristics have advanced from simple evaluation by touch to complex methodologies such as ultrasonography and plethysmography. Today's understanding of the various characteristics of the arterial pulse relies on our ancestors' observations and experiments. The pursuit of science continues to lead to major advancements in our knowledge of the arterial pulse and its application in diagnosis of atherosclerotic disease.
Young women with coronary heart disease have high rates of depression and a higher risk of adverse events than men of similar age. Whether depression has a higher prognostic value in this group than in men and older women is not known. Our objective was to assess whether depression in young women is associated with higher risk of coronary artery disease (CAD) and adverse outcomes compared with similarly aged men and older women.
Cardiac rehabilitation (CR) is recommended for patients with coronary heart disease, however, participation among veterans remains poor. Smartphones may facilitate data transfer and communication between patients and providers, among other benefits. We evaluated the feasibility of a smartphone-enabled CR program in a population of veterans. Qualifying veterans were prospectively enrolled in a single-arm, nonrandomized feasibility study of a smartphone-enabled, home-based CR program, featuring an app with daily reminders to exercise, log vitals, and review educational materials. A coach remotely monitored patients through an online dashboard and scheduled telephone visits. Clinical end points were assessed as an exploratory aim. After 21 veterans provided informed consent, 18 were enrolled and successfully completed at least 30 days of the program; 13 completed the entire 12-week intervention. Mean (standard deviation) age was 62 (7) years and 96% were male. Program completers logged a mean (standard deviation) of 3.5 (1.4) exercise sessions and 150 (86) exercise minutes per week. The majority (84%) of program completers reported being satisfied overall with the program. Mean functional capacity improved by 1.0 metabolic equivalents (5.3 to 6.3, 95% confidence interval 0.3 to 1.7; p = 0.008) and mean systolic blood pressure at rest improved by 9.6 mm Hg (mean difference 9.6, 95% confidence interval −19.0 to −0.7; p = 0.049) among completers. Smartphone-enabled, home-based CR is feasible in veterans with heart disease and is associated with moderate to high levels of engagement and patient satisfaction.
Background
Genome-wide association studies have identified multiple variants associating with coronary artery disease (CAD) and myocardial infarction (MI). Whether a combined genetic risk score (GRS) is associated with prevalent and incident MI in high risk subjects remains to be established.
Methods and Results
In subjects undergoing cardiac catheterization (n=2597) we identified cases with a history of MI onset at age <70 years and controls ≥70 years old without prior MI, and followed them for incident MI and death. Genotyping was performed for 11 established CAD/MI variants and a GRS calculated based on average number of risk alleles carried at each locus weighted by effect size. Replication of association findings was sought in an independent angiographic cohort (n=2702). The GRS was significantly associated with prevalent MI, occurring before age 70 years, compared to older controls (≥70 years) with no history of MI (p<0.001). This association was successfully replicated in a second cohort yielding a pooled p value of <0.001. The GRS modestly improved the c-statistic in models of prevalent MI with traditional risk factors. However, the association was not statistically significant when elderly controls without MI but with stable angiographic CAD were examined (pooled p=0.11). Finally, during a median 2.5 year follow-up, only a non-significant trend was noted between the GRS and incident events, which was also not significant in the replication cohort.
Conclusions
A GRS of 11 CAD/MI variants is associated with prevalent MI but not near term incident adverse events in two independent angiographic cohorts. These findings have implications for understanding the clinical utility of genetic risk scores for secondary as opposed to primary risk prediction.
Background
Multiple scoring systems have been devised to quantify angiographic coronary artery disease (CAD) burden, but it is unclear how these scores relate to each other and which scores are most accurate. The aim of this study was to compare coronary angiographic scoring systems 1) with each other and 2) with intravascular ultrasound (IVUS) derived plaque burden in a population undergoing angiographic evaluation for CAD.
Methods
Coronary angiographic data from 3600 patients was scored using 10 commonly used angiographic scoring systems and inter-score correlations were calculated. In a subset of 50 patients, plaque burden and plaque area in the left anterior descending coronary artery was quantified using IVUS and correlated with angiographic scores.
Results
All angiographic scores correlated with each other (range for Spearman coefficient (ρ): 0.79-0.98, p<0.0001); the two most widely used scores, Gensini and CASS-70, had a ρ = 0.90, p<0.0001. All scores correlated significantly with average plaque burden and plaque area by IVUS (range ρ: 0.56-0.78, p<0.0001 and 0.43-0.62, p<0.01, respectively). The CASS-50 score had the strongest correlation (ρ: 0.78 and 0.62, p<0.0001) and the Duke Jeopardy score the weakest correlation (ρ: 0.56 and 0.43, p<0.01) with plaque burden and area, respectively.
Conclusions
Angiographic scoring systems are strongly correlated with each other and with atherosclerotic plaque burden. Scoring systems therefore appear to be a valid estimate of CAD plaque burden.