Patrick Campbell

This article was originally published on 

Data from an analysis of the multinational CLARIFY registry is helping to paint a clearer picture of the relationship between coronary syndromes and diabetes. 

The study found patients with chronic coronary syndromes were 3 times more likely to have diabetes and also revealed these patients were at a much greater risk of future cardiovascular events, including stroke, myocardial infarction, and cardiovascular death.

"Obesity and lack of exercise are common risk factors for both diabetes and heart disease and our results highlight the urgent need to improve nutrition and raise activity levels globally," said study lead investigator Emmanuelle Vidal-Petiot, MD, PhD, of Bichat-Claude Bernard Hospital, Paris, France,

. "Countries worst affected by diabetes are also at the epicentre of the obesity epidemic, which can be in part attributed to urbanization and associated changes in physical activity and food intake."

Published on World Health Day, the study was conducted by Vidal-Petiot and a team of colleagues with the intent of further exploring the prognostic impact of diabetes in patients presenting with chronic coronary syndromes. With this in mind, the study was designed as an analysis of data from within the CLARIFY registry.

A prospective, international registry, CLARIFY provided investigators with information related to more than 30,000 patients with stable coronary artery disease from 45 middle- and high-income countries followed for 5 years beginning in 2009-2010. For inclusion in the registry, patients needed to have had a documented myocardial infarction more than 3 prior, coronary angiography revealing a blockage of 50% or more, history of CABG or PCI more than 3 months prior, or proven symptomatic myocardial ischemia.

Of note, multiple investigators of the current study were on the executive committee or served as investigators in the original CLARIFY study. 

For the current analysis, investigators chose a composite outcome of cardiovascular death, myocardial infarction, and stroke as the primary outcome. Secondary outcomes for the analysis included each component of the primary outcome, total death, and hospitalization for heart failure.

After the exclusion of 9 patients from the CLARIFY registry due to lack of diabetes information, a cohort of 32,694 patients were identified for inclusion. Among these, 9502 (29%) had diabetes. Investigators noted the prevalence of diabetes ranged from 14% in Ireland to 67% in Saudi Arabia.

At the end of the 5-year follow-up period, 2807 patients had met the primary composite endpoint and 2544 patients had died, including 1619 who died from cardiovascular causes. When assessing secondary endpoints, investigators found stroke occurred in 686 patients, myocardial infarction occurred in 1106, 1647 patients were hospitalized for heart failure, and 2526 patients underwent coronary revascularization.

Upon analysis, all adverse clinical outcomes of interest occurred more frequently among patients diabetes. In adjusted analyses, patients with diabetes had a 28% greater risk for the primary composite outcome (aHR, 1.28; 95% CI, 1.18-1.39) and a greater risk for all secondary outcomes.

For secondary outcomes, patients with diabetes were at a 38% (HR, 1.38; 95% CI, 1.18-1.39) risk of all-cause death, a 39% (HR, 1.39; 95% CI, 1.25-1.54) greater risk of cardiovascular death, a 26% (HR, 1.26; 95% CI, 1.10-1.43) greater risk for myocardial infarction, a 29% (HR, 1.29; 95% CI, 1.09-1.52) greater risk of stroke, a 15% (HR, 1.15; 95% CI, 1.03-1.28) greater risk for hospitalization for heart failure, and a 14% (HR, 1.14; 95% CI, 1.04-1.25) greater risk of coronary revascularization.

"The importance of healthy eating and living cannot be overemphasized. Everyone can lower their chances of developing diabetes with weight control and exercise, and early detection is needed so that blood sugar can be controlled,” noted Vidal-Petiot. “Those with heart disease and diabetes also need an active lifestyle and a good diet to protect their health. Avoiding smoking is crucial, as is controlling blood pressure and cholesterol levels."

Prevalence of diabetes and impact on cardiovascular events and mortality in patients with chronic coronary syndromes, across multiple geographical regions and ethnicities

European Journal of Preventive Cardiology.

Articles

An analysis of the CLARIFY registry is providing clinicians with further insight into the impact of diabetes in patients with chronic coronary syndromes, particularly the increased risk of stroke, myocardial infarction, and cardiovascular death.

CLARIFY: Diabetes Poses Major Risk in Patients with Coronary Syndromes

New research provides evidence suggesting survivors of preterm birth were at an increased risk of new-onset heart failure that persisted through adulthood.

An analysis of data from nearly 4.2 million patients in a Swedish birth registry dating back to 1973, results of the study indicate being born before 37 weeks gestational age was associated with a greater risk of heart failure at multiple stages of life—underlining the need for greater follow-up and monitoring of this patient population.

“To our knowledge, this is the largest population-based study of preterm birth in association with HF risks and the first to examine such risks into mid-adulthood or include cosibling analyses,” wrote investigators.

Spurred by an interest in furthering the understanding of preterm birth and cardiovascular risk later in life, a team led by Casey Crump, MD, PhD, of the Ichan School of Medicine at Mount Sinai, sought to address these apparent knowledge gaps using data from the Swedish Birth Register. Using a time frame of 1973-2018, the registry provided investigators with data related to 4,193,069 live singleton births, including 210,039 preterm births.

The median age of the study cohort was 22.5 years and the maximum age was 43 years. In total, investigators obtained data related to 85.0 million person-years of follow-up. Of those born preterm, 8324 were considered extremely preterm (22-27 weeks), 44,373 were moderately preterm (28-33 weeks), 157,342 were late preterm (34-36 weeks), and 740,391 were early term (37-38 weeks). In regard to the remaining patients, 2,896,444 were considered full term births and 346,195 were considered postterm births.

The primary outcome measure of the study was incident heart failure. For the purpose of analysis, investigates planned to use Cox regression to determine hazard ratios associated with each gestational age group while adjusting for perinatal and maternal factors. Investigators also planned additional cosibling analyses to assess for potential confounding by unmeasured familial factors.

Upon analysis, investigators identified 4158 patients as having heart failure. These patients had a median age at diagnosis of 15.4 (IQR, 28.0) years at diagnosis. Adjusted analyses indicated preterm birth, defined as earlier than 37 weeks, was associated with an increased risk of heart failure at ages younger than 1 year (aHR, 4.49; 95% CI, 3.86-5.22), 1-17 years (aHR, 3.42; 95% CI, 2.75-4.27), and 18-43 years (aHR, 1.42; 95% CI, 1.19-1.71) when compared to full term births.

At ages 18-43 years, the hazard ratios stratified by gestational age were 4.72 (95% CI, 2.11-10.52) for extremely preterm births, 1.93 (95% CI, 1.37-2.71) for moderately preterm births, 1.24 (95% CI, 1.00-1.54) for late preterm births, and 1.09 (95% CI, 0.97-1.24) for early term births. Investigators noted the corresponding incidence rates for patients at 18-43 years were 31.7, 13.8, 8.7, and 7.3, respectively, compared with 6.6 for full term births

Investigators included 3.5 million individuals in their cosibling analyses. Results of these analyses were similar to that of the primary analyses when assessing risk among patients younger than 18 years but substantially lower risks were no longer significant at ages 18-43 years.

, Mandy Brown Belfort, MD, MPH, of Brigham and Women’s Hospital, and Suzanne Brown Sacks, MD, MS, of Vanderbilt University School of Medicine, commended investigators on bringing attention to the importance of shifting focus to long-term health of survivors of preterm birth.

“The findings by Crump et al shed new light on heart failure as a long-term consequence of preterm birth and highlight opportunities for clinicians caring for preterm-born infants across the lifespan to understand their unique health risks and tailor their preventive and disease-specific care accordingly,” wrote the pair.

Association of Preterm Birth With Long-term Risk of Heart Failure Into Adulthood

An analysis of nearly 4.2 million patients from a birth registry indicates being born preterm was linked to a significantly higher risk of developing heart failure during childhood and a 42% greater risk of heart failure in adulthood.

Preterm Birth Associated with Increased Heart Failure Risk Throughout Adulthood

Patients with peripheral artery disease (PAD) who do not experience ischemic leg pain during their walking program could be failing to reach a threshold that provides any meaningful benefit, according to the results of a new trial from Northwestern Medicine.

Results of the study demonstrate participating in a low-intensity exercise program failed to achieve a meaningful difference compared to no exercise at all, while high-intensity walking that induced ischemic leg symptoms was associated with significant improvements in 6-minute walking distance and walking impairment at 12 months.

"We've shown you have to walk to elicit ischemic leg pain to reap the benefits," said lead investigator Mary McDermott, MD, professor of medicine at Northwestern University Feinberg School of Medicine, 

. "It will lessen over time, and most people eventually will be able to walk further without discomfort."

After a previous study found pain during exercise was a primary reason cited for inability to continue a walking program, McDermott and team designed the Low-Intensity Exercise Intervention in PAD (LITE) randomized clinical trial to assess whether a low-intensity walking exercise intervention that does not induce ischemic leg pain improved walking distance in patients with PAD compared to a high-intensity intervention inducing ischemic leg symptoms and a nonexercise control group.

Funded by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health, the LITE trial randomized 305 patients in a 120:120:65 ratio using a SAS computer program between September 25, 2015 and December 11, 2019. These patients were recruited from 4 US medical centers and followed for 12 months after randomization. Of note, the final follow-up occurred on October 7, 2020.

To be included in LITE, patients needed to have an ankle-brachial index (ABI) of 0.90 or less in either leg. Exclusion criteria for the trial included major amputation, a MiniMental State Examination score of less than 23, use of a walking aid other than a cane, having a walking limitation for a reason other than PAD, and having a significant visual or hearing impairment, among others.

Investigators received written informed consent from 441 patients with PAD and 305 underwent randomization. Of these, 116 patients were randomized to low-intensity walking, 124 were randomized to high-intensity walking, and 65 were randomized to the nonexercise control. The overall study population had a mean age of 69.3 (SD, 9.5) years, 47.9% were women, and 59.3% were Black. In total, 250 participants completed the 12-month follow-up.

Patients randomized to an exercise group were asked to walk for exercise 5 times per week for up to 50 minutes per session and wear an accelerometer to document exercise use intensity and time. For the purpose of analysis, the high-intensity group walked at a pace eliciting moderate to severe ischemic leg symptoms while the low-intensity group walked at a pace eliciting no ischemic leg symptoms.

The primary outcome for the trial was mean change in 6-minute walk distance at 12 months. Investigators pointed out a distance of 8-20 meters was used as a threshold for minimum clinically important difference at 12 months.

Upon analysis, investigators found 6-minute walk distance had changed from 332.1 meters at baseline to 327.5 meters in the low-intensity exercise group (within-group mean change, -6.4 meters; 95% CI, -21.5 to 8.8; 

=.34) and from 338.1 meters to 371.2 meters in the high-intensity exercise group (within-group mean change, 34.5 meters; 95% CI, 20.1 to 48.9; 

 <.001) at 12-month follow-up. Based on these results, investigators determined the mean change for the between-group comparison was -40.9 m (97.5% CI, -61.7 to -20.0; 

In the nonexercise control group, 6-minute walk distance changed from 328.1 meters at baseline to 317.5 meters at 12-month follow-up p (within-group mean change, -15.1 meters; 95% CI, -35.8 to 5.7; 

=.10), which investigators highlighted was not significantly different from the change observed in the low-intensity exercise group (between-group mean change, 8.7 meters; 97.5% CI, -17.0 to 34.4; 

A safety analysis revealed 2 serious adverse events were considered study-related. These events were a transient supraventricular arrhythmia developing after the baseline exercise stress test and needing to undergo coronary artery stent placement after chest discomfort developed while exercising in the low-intensity group.

McDermott and colleagues noted future plans to evaluate the biological expiation for the association between ischemia of the lower extremities and apparent benefit from walking exercise.

Effect of Low-Intensity vs High-Intensity Home-Based Walking Exercise on Walk Distance in Patients With Peripheral Artery Disease

Results of a 305-patient trial indicate ischemic leg pain could serve as a threshold for whether or not a patient with peripheral artery disease will see a meaningful improvement in walking score from their walking routine. 

LITE Trial: Low-Intensity Walking Provides Little to No Benefit for PAD Patients

6:50 - Barriers to Incorporating PROs in Practice

In this episode, Stephen Greene, MD, of the Duke Clinical Research Institute, breaks down a recent study he led comparing the sensitivity of NYHA class versus patient-reported outcomes for capturing changes in disease state among patients with heart failure with reduced ejection fraction.

Briefly, the study used data from the CHAMP-HF registry to identify a cohort of more than 2k HFrEF patients and found PRO, as measured by the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS), was more sensitive and better at tracking meaningful changes in health status over time when compared to use of NYHA class.

For more on use of KCCQ-OS vs. NYHA class, check out our coverage of Greene's study. 

Podcasts

Hear from Stephen Greene, MD, as he takes a deeper dive into a recent study he led comparing use of NYHA class vs. KCCQ-OS to capture changes in disease state among patients with heart failure with reduced ejection fraction. 

Patrick Campbell

Articles

CLARIFY: Diabetes Poses Major Risk in Patients with Coronary Syndromes

Preterm Birth Associated with Increased Heart Failure Risk Throughout Adulthood

LITE Trial: Low-Intensity Walking Provides Little to No Benefit for PAD Patients

Implementation and Use of Patient-Reported Outcomes in Heart Failure with Stephen Greene, MD