Peripheral Arterial Disease

Abbreviations
Abbreviation	Definition	Note
PAD	Peripheral Arterial Disease
ABI	Ankle-Brachial Index	The ankle-brachial index test compares the blood pressure measured at your ankle with the blood pressure measured at your arm. It is a method of checking for PAD.

[ABI-Definition]

Disease Overview 

Patients with peripheral arterial disease (PAD) have decreased lower extremity arterial perfusion which is commonly referred to as “poor circulation.” In most cases of PAD, atherosclerotic plaques narrow the arterial flow lumen which restricts blood flow to the distal extremity. Reduced blood flow can cause thigh or calf pain with walking due to temporary ischemia of the leg muscles during exertion. Walking pain from PAD is referred to as intermittent claudication which means “to limp.” Many patients with PAD have either no symptoms or atypical complaints that do not strictly conform to the definition of claudication. Others may develop limb-threatening compromise of blood flow, necessitating emergent surgery. PAD acts as a marker for systemic atherosclerosis. PAD usually involves atherosclerotic disease in the abdominal aorta, iliac, and femoral arteries. The pathophysiology of atherosclerosis involves complex interactions between cholesterol and vascular cells. Atherosclerotic plaque builds up slowly on the inside of arteries. In the early stages of PAD, the arteries compensate for the plaque buildup by dilating to preserve flow through the vessel. Eventually, the artery cannot dilate any further, and the atherosclerotic plaque starts to narrow the arterial flow lumen. [PAD-Definition]

GBD 2019 Modeling Strategy 

Non-Fatal Modeling Strategy

Peripheral arterial disease was defined as having an ankle-brachial index (ABI) < 0.9. Intermittent claudication was defined clinically. Administrative claims data were adjusted to the reference (prevalence of PAD based on directly-measured ABI values) using MR-BRT.

We used the proportion of intermittent claudication to split the overall prevalence of peripheral arterial disease into symptomatic and asymptomatic peripheral vascular disease. The table below illustrates these values:

Details on the severity levels for Peripheral Arterial Disease in GBD 2019 and the associated disability weight (DW) with that severity.

Severity Distribution
Severity level	Lay description	DW (95% CI)
Asymptomatic	No symptoms	No DW assigned
Symptomatic	Has cramping pains in the legs after walking a medium distance. The pain goes away after a short rest.	0.014 (0.007–0.025)

DisMod-MR 2.1 was used to model both the overall prevalence of PAD and the proportion of peripheral arterial disease with intermittent claudication. To obtain final estimates for the sequelae of interest, we multiplied the prevalence model by the proportion model at the draw level to generate the prevalence of symptomatic and asymptomatic peripheral vascular disease.

Fatal Modeling Strategy

We included vital registration data in a standard CODEm approach to model peripheral artery disease.

Cause Hierarchy

Restrictions

GBD 2019 Cause Restrictions
Restriction Type	Value	Notes
Male only	False
Female only	False
YLL only	False
YLD only	False
YLL age group start	40	[40, 44 years), age_group_id=13
YLL age group end	125	[95, 125 years), age_group_id=235
YLD age group start	40	[40, 44 years), age_group_id=13
YLD age group end	125	[95, 125 years), age_group_id=235

Vivarium Modeling Strategy 

Scope

PAD should occur at the incidence of PAD in the DisMod model. PAD is then a chronic state without remission. Transition from prevalent PAD to death should occur at the GBD EMR rate for PAD from the PAD DisMod model. The transition rate from the susceptible state to the prevalent state should be modified by fasting plasma glucose, smoking, systolic blood pressure, and impaired kidney function.

Assumptions and Limitations

PAD is highly comorbid with ischemic heart disease (IHD). Because of this, persons with PAD have high with-condition mortality, but low cause-specific mortality.

Cause Model Diagram

State and Transition Data Tables

Definitions

State Definitions
State	State Name	Definition
S	Susceptible to PAD	Simulant that has not been diagnosed with PAD.
P	Peripheral arterial disease	Simulant with prevalent PAD (ankle-brachial index <=0.9)
D	Death	Simulant that has experienced death at the rate of the EMR from the DisMod model

States Data

States Data
State	Measure	Value	Notes
All	cause-specific mortality (CSMR)	\(\frac{\text{deaths\_c502}}{\text{population}}\)	Post CoDCorrect cause-level CSMR
S	prevalence	\(1 - \text{prevalence\_c502}\)
P	prevalence	\(\sum\limits_{s \in \text{sequelae}} \text{prevalence}_s\)	There are two chronic sequalae
D	prevalence	0
S	excess mortality	0
P	excess mortality	\(\text{emr\_m2532}\)
S	disability weight	0
P	disability weights	\(\frac{1}{\text{prevalence\_c502}} \times \sum\limits_{s \in \text{sequelae}} \text{disability\_weight}_s \cdot \text{prevalence}_s\)
D	disability weight	0

Transition Data

Transition Data
State	Source State	Sink State	Value	Notes
1	S	P	incidence_c502	This is cause-level incidence which is equivalent to the “population rate”
2	P	D	emr_m2532

Data Sources

This table contains the data sources for all the measures. The table structure and common measures are as below:

Data Sources and Definitions
Value	Sources	Description	Notes
prevalence_c502	como	Prevalence of peripheral arterial disease
deaths_c502	codcorrect	Deaths from peripheral arterial disease
incidence_c502	como	Incidence of ischemic stroke	This is the population incidence rate for peripheral arterial disease
population	demography	Mid-year population for given age/sex/year/location
sequelae_c502	gbd_mapping	List of 2 sequelae for peripheral arterial disease
prevalence_s{sid}	como	Prevalence of sequela with id sid
disability_weight_s{sid}	YLD appendix	Disability weight of sequela with id sid
emr_m2532	dismod-mr 2.1	excess mortality rate of peripheral arterial disease
sequelae	sequelae definition	{s964, s1041}

Validation Criteria

Compare CSMR experienced by simulants to CSMR from CoDCorrect in GBD
Compare prevalence experienced by simulants to post-COMO prevalence in GBD

References 

[PAD-Definition]

Zemaitis MR, Boll JM, Dreyer MA. Peripheral Arterial Disease. [Updated 2021 Mar 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430745/