Observational Population Health Research

Observational Population Health Research

For over a quarter century, the section has defined vascular disease health challenges and provided answers from diverse study designs. Distinct vascular health questions require different data sources and analytic approaches. Observational data can be informative, but such analyses are potentially challenging. The section creates high impact investigations to inform national vascular health. Examples of recent observational investigations include:

Selected Studies

Calculating Individual Risk for PAD

Calculating Individual Risk for PAD

The “SEE-PAD” PAD Risk Score: Are You At Risk for PAD? (2012):

If PAD is so common, why don’t people – or their doctors – know they have it? What if coronary heart disease were common, and no one used the ECG? Despite over three decades of research defining the high prevalence of PAD, individuals, health professionals, payers and health agencies have not yet effected any efficient plan to determine who has PAD.

The key may be the word “efficient”. If PAD is common, who should be tested? Detection of peripheral artery disease (PAD) typically entails collection of medical history, physical examination, and noninvasive imaging, but this approach is burdensome. This study was designed to create an efficient risk factor-based model that might be used by individuals, health systems, or investigators who are interested in population screening. Analyses were derived from 18,049 US REACH (REduction of Atherothrombosis for Continued Health) Registry outpatients to create a PAD prevalence risk score that was externally validated using the Framingham Offspring Study. This score works and may improve PAD detection in vulnerable, at-risk populations.

Related Article
Duval S, Massaro JM, Jaff MR, Boden WE, Alberts MJ, Califf RA, Eagle KA, D’Agostino RB, Pedley A, Fonarow GC, Murabito JM, Steg G, Bhatt DL, Hirsch AT; on behalf of the REACH Registry Investigators. "An Evidence-Based Score to Detect Prevalent Peripheral Artery Disease (PAD)." Vascular Medicine. 2012 Oct;17(5):342-51.

Determinants of Severe PAD Outcomes

Determinants of Severe PAD Outcomes

The FRIENDS Registry: The Determinants of Severe PAD Outcomes (2014):

It has long been known that individuals with PAD suffer rates of major adverse cardiac events (MACE) and major adverse limb events (MALE) at rates higher than nearly any other cardiovascular disease. Within the five key PAD clinical syndromes, it is individuals with severe PAD, defined as acute limb ischemia (ALI) and chronic critical limb ischemia (CLI), who suffer most.

Yet, despite decades of work to improve outcomes via provision of revascularization alone, it is not clear that either population rates of limb amputation or survival have improved. Why? Is amputation-free survival anticipated to increase via limb procedures alone? For other ischemic diseases (heart attack and stroke), it has long been known that there are many other key determinants of a “good outcome”. The FReedom from Ischemic Events: New Dimensions for Survival” (FRIENDS) Registry, originally created by Dr. Hong Keo, as a University of Minnesota vascular medicine fellow, assessed whether the duration of limb ischemia would serve as a major predictor of limb and patient survival. 
The results of this registry imply that prompt diagnosis and revascularization might improve outcomes for patients with ALI.

Related Article
Duval S, Keo HH, Baumgartner I, Oldenburg NC, Jaff MR, Peacock JM, Tretinyak AS, Henry TD, Luepker RV, Hirsch AT, on behalf of the FRIENDS Investigators. "The Impact of Prolonged Lower Limb Ischemia on Cardiovascular Event Rates, Mortality and Functional Status: The FRIENDS Registry." Am Heart J. 2014 Oct;168(4):577-87.

Epidemiology of PAD and CLI

Epidemiology of PAD and CLI

The USA National Epidemiology of PAD and CLI (2014):

While many data sources have been informative to define the prevalence of PAD in the United States and globally, it is very challenging to define either the incidence or prevalence of critical limb ischemia. There are no national cohort studies of CLI and coding for CLI in national health systems is poor. Similarly, simple measurement of amputation rates may not precisely attribute limb loss to either established PAD or to a new leg ischemic event.

In collaboration with Dr. Mark Nehler, William R. Hiatt, and the Colorado Prevention Center, the USA Marketscan database was analyzed, using a complex technique informed by clinical expertise, to define the incidence and prevalence of both PAD and CLI in the United States.

Merely “guessing” the number of legs lost to CLI via untested mathematical algorithms does not define either the population health challenge, nor the market. It is also preferable to measure disease prevalence directly.

Related Article
Nehler MR, Duval S, Zakharyan A, Annex BH, Diao L, Hiatt WR, Hirsch AT. "Epidemiology of Peripheral Artery Disease and Critical Limb Ischemia in an Insured National Population." J Vasc Surg. 2014 Sep;60(3):686-95.e2. doi: 10.1016/j.jvs.2014.03.290.

Risk of Systemic Embolic Events in Patients with Atrial Fibrillation

Risk of Systemic Embolic Events in Patients with Atrial Fibrillation

The AF–SEE Risk Project: What is the Risk of Systemic Embolic Events in Patients with Atrial Fibrillation? (2015):

Over five million Americans and over 35 million individuals globally suffer from atrial fibrillation (AF). While it is known that atrial fibrillation is a major contributor to the incidence of ischemic stroke, due to contributions of both cardioembolic and atheroembolic etiologies, the cardiac output is also distributed to non-brain arterial circulations and these “systemic embolic events (SEE) must effect vascular health. Yet, to date, this impact was rarely measured, and patients and health professionals have been poorly informed regarding this holistic risk to all major organs.

In collaboration with the McMaster University-based Population Health Research Institute, lead by University fellow, Dr. Wobo Bekwelem, and esteemed international collaborators, an international AF clinical trials dataset has now provided a minimal estimate of the SEE incidence and defined the dangers (mortality equal to that of stroke) of systemic embolic to any non-cerebral arterial bed. It is hoped that these data will inspire the measurement of the vascular disease burden in all patients with AF and will lead to more prompt recognition and treatment of new ischemic events in this vulnerable population.

Related Article
Bekwelem W, Adabag S, Duval S, Chrolavicius S, Pogue J, Halperin JL, Connolly S, Hirsch AT. "Extracranial Systemic Embolic Events in Patients with Atrial Fibrillation: Incidence, Risk Factors, and Outcomes." Circulation. 2015 Sep 1;132(9):796-803.

Impact of Tobacco on PAD Health Outcomes and Cost

Impact of Tobacco on PAD Health Outcomes and Cost

The AHEAD PAD Tobacco Health Impact Analysis: What is the Exact Impact of Tobacco on PAD Health Outcomes and Cost? (2015):

Everyone knows that tobacco use is bad. Tobacco is the single most powerful cause of PAD in every nation, and is associated with nearly 65% of the population-attributable risk of developing PAD. Yet, it seems true that tobacco cessation efforts in the high risk PAD population are not consistently offered to all individuals with PAD who smoke.

Why? Tobacco cessation seems hard, is “no one’s job”, and vascular specialists are neither trained nor incentivized to provide this. What is the cost of this approach to PAD care, to patients, payers and society?

Amazingly, to date, this question had not been evaluated. In collaboration with Blue Cross Blue Shield of Minnesota, the section conducted a retrospective, cross sectional study of over 22,000 individuals with PAD, defined a cohort that smoked, and evaluated the annual rate of hospitalizations, hospitalized diagnoses, and health economic impact. Is there a “value proposition” to inaction on tobacco cessation when the annual cost increment is over $18,000, when half of PAD smokers are hospitalized annually, and a comprehensive quit attempt (using both individualized behavioral and pharmacologic interventions) costs less than $500?

Tobacco cessation is a national ACCF-AHA PAD guideline performance measure. How well does your health system perform? 

Related Article
Duval S, Long KH, Roy SS, Oldenburg NC, Harr K, Alesci NL, Fee RM, Sharma RR; and Hirsch AT. The Contribution of Smoking to High Healthcare Utilization and Medical Costs in Peripheral Artery Disease: A State-Based Insured Cohort Analysis. J Am Coll Cardiol. 2015 Oct 6;66(14):1566-74.

Observations From the SOLID‐TIMI 52 Trial

Observations From the SOLID‐TIMI 52 Trial

Interleukin‐6 and the Risk of Adverse Outcomes in Patients After an Acute Coronary Syndrome: Observations From the SOLID‐TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52) Trial

Initiation and progression of subclinical atherosclerosis to plaque instability and rupture in acute coronary syndrome (ACS) comprise a complex process driven by both vascular lipoprotein accumulation and inflammation.1 Interleukin‐6 (IL‐6) is a cytokine that has been implicated in vascular inflammation2 and the initiation and progression of atherosclerosis and degradation of the fibrous cap contributing to plaque instability.3, 4 IL‐6 propagates inflammation and promotes hepatic hs‐CRP (high‐sensitivity C‐reactive protein) production. Prior studies have demonstrated that higher concentrations of IL‐6 are associated with worse vascular health in individuals without clinical atherosclerosis and are associated with the risk of future myocardial infarction (MI).5, 6 In patients with ST‐elevation MI (STEMI), IL‐6 has been shown to be upregulated at the site of coronary occlusion.7, 8 It has also been suggested that IL‐6 concentration may be useful for identifying those patients with unstable coronary disease who may benefit more from an invasive strategy.9

Interest in IL‐6 as a potential therapeutic target is supported by Mendelian randomization studies that have shown signaling through the IL‐6 receptor to be directly implicated in the development of coronary heart disease.10 Moreover, blockade of the IL‐6 receptor with tocilizumab has been shown to attenuate inflammation and blunt the periprocedural rise in troponin in patients with non‐ST‐elevation MI.11 However, the relationship of IL‐6 with outcomes in patients after ACS remains incompletely defined. This relationship remains of importance because of interest in the IL‐1/IL‐6/CRP axis as a potential therapeutic target.11, 12 As an exploratory analysis, we therefore evaluated the association of IL‐6 with cardiovascular outcomes in a large randomized trial population of an anti‐inflammatory therapeutic in patients after ACS.

Related Article
Christina L. Fanola, David A. Morrow, Christopher P. Cannon, Petr Jarolim, Mary Ann Lukas, Christoph Bode, Judith S. Hochman, Erica L. Goodrich, Eugene Braunwald, Michelle L. O'Donoghue. "Interleukin‐6 and the Risk of Adverse Outcomes in Patients After an Acute Coronary Syndrome: Observations From the SOLID‐TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52) Trial" Journal of the American Heart Association. 2017 Oct 24;6:e005637