Interplay between cardiometabolic risk factors in metabolic dysfunction-associated steatotic liver disease: Clinical evidence on cardiovascular disease

Table 1 Metabolic dysfunction-associated steatotic liver disease diagnostic criteria for adults and children

Adult criteria	Children criteria
Overweight or obesity, BMI ≥ 25 kg/m2 and ≥ 23 kg/m2 for Asia OR WC ≥ 94 cm (M) and ≥ 80 cm (F) for Europeans OR ≥ 90 cm (M) and ≥ 80 cm (F) for South Asians and Chinese OR ≥ 85 cm (M) and ≥ 90 cm (F) for Japanese	Overweight or obesity, BMI ≥ 85th percentile for age/sex (BMI z score ≥ +1) OR WC ≥ 95th percentile OR ethnicity adjusted equivalent
Prediabetes, HbA1c: 5.7%-6.4% OR fasting plasma glucose: 100-125 mg/dL OR 2-hour plasma glucose during OGTT: 140-199 mg/dL OR T2D: HbA1c ≥ 6.5% OR fasting plasma glucose ≥ 126 mg/dL OR 2-hour plasma glucose during OGTT ≥ 200 mg/dL or treatment for T2D	Prediabetes, HbA1c: 5.7%-6.4% OR fasting plasma glucose: 100-125 mg/dL OR 2-hour plasma glucose during OGTT: 140-199 mg/dL OR T2D: HbA1c ≥ 6.5% OR fasting plasma glucose ≥ 126 mg/dL OR 2-hour plasma glucose during OGTT ≥ 200 mg/dL or treatment for T2D
Blood pressure ≥ 130/85 mmHg OR treatment for hypertension	Blood pressure age < 13 year, BP ≥ 95th percentile OR ≥ 130/85 mmHg; age ≥ 13 years, ≥ 130/85 mmHg OR treatment for hypertension
Plasma triglycerides ≥ 150 mg/dL OR lipid-lowering treatment	Plasma triglycerides age < 10 years, ≥ 100 mg/dL; age ≥ 10 years, ≥ 150 mg/dL OR lipid-lowering treatment
Plasma HDL-cholesterol ≤ 40 mg/dL (M) and ≤ 50 mg/dL (F) OR lipid-lowering treatment	Plasma HDL-cholesterol ≤ 40 mg/dL OR lipid-lowering treatment

Steatotic liver disease: Hepatic steatosis determined by imaging or biopsy. Presence of at least 1 of 5 cardiometabolic criteria without other causes of steatosis. BMI: Body mass index; F: Female; M: Male; WC: Waist circumference; HbA1c: Glycated hemoglobin; OGTT: Oral glucose tolerance test; T2D: Type 2 diabetes; HDL: High-density lipoprotein; BP: Blood pressure.

Table 2 Overview of risk factors associated to metabolic dysfunction-associated steatotic liver disease

Obesity-associated risk factors of MASLD
Lifestyle choices: Poor dietary habits; Less physical activity
Inherent risk factors: Genetic predisposition; Race/ethnicity (hispanic race); Sex (men); Epigenetic influences
Influence of metabolic factors: Dyslipidemia; Insulin resistance; Type 2 diabetes; Hypertension
Pathological processes: Gut microbiota; Adipokine imbalance; Systemic inflammation; Oxidative stress; Immune system imbalance; Hepatic steatosis

MASLD: Metabolic dysfunction-associated steatotic liver disease.

Table 3 Network of cardiometabolic risk factors between metabolic dysfunction-associated steatotic liver disease and cardiovascular disease

Factor	Key drivers/mechanisms	Relationship to MASLD and CVD
Obesity and visceral fat	High energy intake leads to hypertrophy of adipocytes in the adipose tissue	BMI and waist circumference positively correlate with MASLD progression. Visceral adipose tissue mediates the majority of cardiometabolic risk by promoting insulin resistance
Insulin resistance	Disruption of metabolic pathways in muscle, liver, and adipose tissue. Driven by hyperinsulinemia and lipotoxicity	Creates a vicious cycle with hepatic steatosis. Insulin resistance exacerbates dyslipidemia and endothelial dysfunction and is the most important factor driving atherosclerotic CVD
Dyslipidemia	Increased VLDL-cholesterol synthesis, elevated triglycerides, and reduced HDL-cholesterol (atherogenic profile)	Enhance atherogenesis. Affects a high percentage of MASLD/MASH patients. Promotes plaque formation and increased risk of myocardial infarction
Systemic inflammation	Secretion of pro-inflammatory adipokines (TNF-α, IL-6, CRP) and reduced adiponectin	Cytokines from the diseased liver drain into circulation, intensifying a systemic pro-inflammatory state that leads to CVD. Promotes vascular injury, atherosclerosis
Oxidative stress	Imbalance between ROS and antioxidants (e.g., low glutathione)	High ROS levels cause mitochondrial dysfunction and hepatocyte apoptosis, leading to fibrosis (MASH). Promotes plaque instability
Endothelial dysfunction	Reduced nitric oxide bioavailability and increased ADMA or endothelin-1	An early event linking MASLD to CVD. Correlates with the severity of liver steatosis and arterial stiffening. Promotes thrombosis
Hypertension	Activation of the RAAS and sympathetic nervous system	Bidirectional relationship: Hypertension aggravates liver damage, while MASLD influences high blood pressure development

VLDL: Very low-density lipoprotein; HDL: High-density lipoprotein; TNF-α: Tumor necrosis factor-alpha; IL-6: Interleukin-6; CRP: C-reactive protein; ROS: Reactive oxygen species; ADMA: Asymmetric dimethylarginine; RAAS: Renin-angiotensin-aldosterone system; MASLD: Metabolic dysfunction-associated steatotic liver disease; BMI: Body mass index; CVD: Cardiovascular disease; MASH: Metabolic dysfunction-associated steatohepatitis.

Table 4 Representative clinical studies on the association between metabolic dysfunction-associated steatotic liver disease and cardiovascular disease

Ref.	Country, year	Type of study	Population, diagnostic method	Main outcomes
Subclinical atherosclerosis and arterial stiffness
Kim et al[193]	South Korea, 2012	Cross-sectional study	4023 subjects (ultrasonography)	CAC scores were associated with a higher prevalence of MASLD (OR = 1.84, 95%CI: 1.61-2.10). CAC scores were significantly associated with MASLD (OR = 1.28, 95%CI: 1.04-1.59) independent of visceral adiposity
Huang et al[196]	China, 2012	Cross-sectional study	8632 participants (ultrasonography)	MASLD had remarkably higher CIMT and ba-PWV compared to the control group (0.594 ± 0.105 mm vs 0.578 ± 0.109 mm and 1665 ± 424 cm/second vs 1558 ± 430 cm/second)
Targher et al[173]	Italy, 2016	Meta-analysis	16 studies; 34043 adult individuals (imaging or histology)	MASLD had a higher risk of fatal and/or non-fatal CVD events (OR = 1.64, 95%CI: 1.26-2.13). Severe MASLD had more development of fatal and non-fatal CVD events (OR = 2.58, 95%CI: 1.78-3.75)
Zhou et al[194]	China, 2018	Systematic review and meta-analysis)	26 studies; 85395 participants (ultrasonography, computed tomography, or biopsy)	MASLD was independently associated with subclinical atherosclerosis (OR = 1.60, 95%CI: 1.45-1.78). MASLD also increased the risk of carotid artery intima-media thickness/plaques, arterial stiffness, CAC, and endothelial dysfunction with OR and 95%CIs of 1.74 (1.47-2.06), 1.56 (1.24-1.96), 1.40 (1.22-1.60), and 3.73 (0.99-14.09), respectively
Wong et al[195]	Singapore, 2018	Meta-analysis	64 studies; 172385 participants (ultrasonography, liver biopsy, CT, MRS, or FLI)	MASLD was associated with increased CIMT (OR 2.00, 95%CI: 1.56-2.56). MASLD was also associated with any coronary calcification (OR = 1.21, 95%CI: 1.12-1.32) and the development/progression of CAC (OR = 1.26, 95%CI: 1.04-1.52)
Liu et al[199]	United States, 2012	Cross-sectional study	2884 participants (CT)	Liver attenuation was inversely associated with CAC in data adjusted for age and sex (OR = 0.84, 95%CI: 0.7-0.9). Fatty liver was associated with CAC independent of abdominal VAT or BMI in African Americans
Guo et al[202]	China, 2017	Cross-sectional study	8571 patients	The prevalence of carotid (56.5% vs 44.5%) and lower limb plaque (56.2% vs 48.7%) and carotid (11.2% vs 6.8%) and lower limb stenosis (15.1% vs 10.3%) were significantly higher in diabetic patients with MASLD compared to those without it (P < 0.001)
Lee et al[206]	South Korea, 2018	Cross-sectional study	5121 individuals (ultrasonography)	Atherosclerotic plaque (OR = 1.18, 95%CI: 1.03-1.35) and non-calcified plaque (OR = 1.27, 95%CI: 1.08-1.48) were significantly higher in MASLD. There was a significant association of FLI ≥ 30 with non-calcified plaque (OR = 1.37, 95%CI: 1.14-1.65) and NFS ≥ -1.455 with non-calcified plaque (OR = 1.20, 95%CI: 1.08-1.42)
Park et al[208]	South Korea, 2019	Retrospective cohort	488 subjects (FibroScan)	CAP ≥ 222 dB/m was independently associated with the presence of coronary plaques (OR = 1.624, 95%CI: 1.047-2.518). CAP ≥ 222 dB/m was significantly associated with non-calcified plaque (OR = 3.528, 95%CI: 1.463-8.511)
VanWagner et al[210]	United States, 2014	Cross-sectional study	2424 participants (CT)	MASLD was associated with CAC (OR = 1.33, 95%CI: 1.001-1.82) and AAC (OR = 1.74, 95%CI: 1.29-2.35). However, these associations were attenuated after adjustment for VAT (CAC OR = 1.05, 95%CI: 0.74-1.48; AAC OR = 1.20, 95%CI: 0.86-1.67)
Cerebrovascular disease and stroke
Wang et al[213]	China, 2022	Meta-analysis	18 studies; 17031672 participants (ultrasonography, CT, MRI, or FLI)	MASLD was associated with a mildly increased risk of stroke (OR = 1.18, 95%CI: 1.08-1.30)
Chen et al[215]	China, 2023	Large prospective cohort study	325129 participants years (FLI)	MASLD was significantly associated with myocardial infarction (HR = 1.35, 95%CI: 1.29-1.41) or stroke (HR = 1.26, 95%CI: 1.18-1.33)
Tang et al[216]	Singapore, 2022	Meta-analysis	30 studies; 7951 patients (biopsy, ultrasonography, CT)	In individuals with MASLD, the incidence of stroke was 5.04% (95%CI: 2.74%-9.09%)
Mahfood Haddad et al[174]	United States, 2017	Systematic review and meta-analysis	6 studies; 25837 patients (elevated transaminases without imaging confirmation)	MASLD had a significantly higher risk of CVE compared to controls (RR = 1.77, 95%CI: 1.26-2.48), while clinical CAD (RR = 2.26, 95%CI: 1.04-4.92) and ischemic stroke (RR = 2.09, 95%CI: 1.46-2.98) were also increased
Alon et al[273]	Italy, 2022	Systematic review and meta-analysis	3254 records; 20 studies (ultrasonography, CT, ICD codes, FLI)	MASLD was associated with an increased risk of MI (OR = 1.66, 95%CI: 1.39-1.99, 95%PI: 0.84-3.30), IS (OR = 1.41, 95%CI: 1.29-1.55, 95%PI: 1.03-1.93), AF (OR = 1.27, 95%CI: 1.18-1.37, 95%PI: 1.07-1.52), and HF (OR = 1.62, 95%CI: 1.43-1.84, 95%PI: 1.04-2.51)
Coronary artery disease and myocardial infarction
Lu et al[223]	China, 2022	Retrospective cross-sectional study	1346 patients (ultrasonography)	The FIB-4 score and NFS were independently associated with CAD. The AST to platelet ratio index was not a significant factor for CAD
Namakchian et al[224]	Iran, 2023	Prospective study	1664 patients (ultrasonography)	FIB-4 score independently correlates with CAD in patients with MASLD
Gastaldelli et al[225]	Italy, 2009	Prospective, observational, cohort study	1307 subjects; 19 centers in 14 European countries (FLI)	FLI was associated with increased CHD risk (r = 0.48)
Wong et al[230]	China, 2011	Prospective cohort study	612 patients (ultrasonography)	After adjusting for demographic and metabolic factors, MASLD (OR = 2.31, 95%CI: 1.46-3.64) remained independently associated with CAD
Toh et al[231]	Singapore, 2022	Meta-analysis	38 articles; 67070 patients (ultrasonography or CT)	The prevalence of CHD was higher in patients with moderate to severe steatosis (37.5%, 95%CI: 15.0%-67.2%) than in those with mild steatosis (29.6%, 95%CI: 13.1%-54.0%)
Emre et al[234]	Turkey, 2015	Prospective cohort study	186 patients (ultrasonography)	Patients with an MASLD score ≥ 3 were more likely to have absent myocardial perfusion (MBG 0/1, 37% vs 12%), absent STR (27% vs 9%), and a higher in-hospital MACE rate (31% vs 8%)
Koh et al[236]	Singapore, 2025	Retrospective observational cohort	5702 patients (HSI)	Non-obesity MASLD had the highest risk of heart failure (P = 0.034), cardiogenic shock (P < 0.001), and all-cause long-term mortality (P = 0.019). The non-obesity MASLD (HR = 1.400, 95%CI: 1.077-1.820, P = 0.012) and obesity MASLD phenotypes (HR = 1.222, 95%CI: 1.005-1.485, P = 0.044) were independently associated with long-term all-cause mortality
Sinn et al[237]	South Korea, 2020	Retrospective cohort analysis	111492 adults over 40 years old (ultrasonography)	Myocardial infarction had an incidence rate of 0.3 cases per 1000 person-years. The age-, sex-, and year-of-visit-adjusted HR for incident myocardial infarction comparing participants with MASLD with those without it was 2.14 (95%CI: 1.59-2.89)
Alexander et al[238]	England, 2019	Matched cohort study	120795 adults (method not reported)	After adjustment for age and smoking, the pooled HR for AMI was 1.17 (95%CI: 1.05-1.30)
Heart failure and structural heart changes
Houghton et al[220]	England, 2019	Cross-sectional study	96 sedentary patients (MRS)	Diastolic variability and systolic variability [LF/HF-SBP (n/1); 2.3 (1.7) vs 3.4 (1.5), P < 0.01] were impaired in patients with MASLD when compared to controls
Targher et al[240]	Italy, 2021	Observational study	356 individuals (ultrasonography)	Individuals with T2D and MASLD (OR = 4.29, 95%CI: 1.90-10.6) and individuals with MASLD alone (OR = 3.41, 95%CI: 1.59-7.29) had an increased risk of having cardiac sympathetic/parasympathetic imbalance
Roderburg et al[243]	Germany, 2023	Retrospective cohort study	173966 patients (method not reported)	MASLD was significantly associated with a subsequent diagnosis of HF (HR = 1.34, 95%CI: 1.28-1.39)
Wu et al[245]	China, 2024	Prospective cohort	96576 participants (ultrasonography)	MASLD was associated with a higher risk of HF (HR = 1.45, 95%CI: 1.31-1.63). In women, MASLD was associated with an 84% increased risk of HF (HR = 1.84, 95%CI: 1.43-2.37), while in men, the risk was 36% (HR = 1.36, 95%CI: 1.20-1.53)
Li et al[247]	China, 2022	A meta-analysis of observational studies	6 cohort studies; 10979967 participants (CT, FLI, biopsy)	In the unadjusted model, MASLD had a greater risk of incident HF (HR = 1.47, 95%CI: 1.25-1.75, I2 = 99%), compared with those without MASLD
Mantovani et al[122]	Italy, 2015	Cross-sectional study	222 patients (ultrasonography)	Patients with MASLD had a remarkably greater prevalence of mild and/or moderate LVDD compared with those without MASLD (71% vs 33%, P < 0.001)
Jung et al[248]	South Korea, 2017	Cross-sectional study	20821 participants (ultrasonography)	The mild and moderate-to-severe MASLD had higher OR for abnormal LV relaxation (mild group 1.29, 95%CI: 1.15-1.46; moderate-to-severe group 1.95, 95%CI: 1.61-2.35) and increased relative wall thickness (> 0.42; mild group 1.26, 95%CI: 1.05-1.52; moderate-to-severe group 1.46, 95%CI: 1.08-1.95)
Fallo et al[249]	Italy, 2009	Observational cross-sectional study	86 patients (ultrasonography)	Patients with MASLD had a similar prevalence of LVH compared to patients without MASLD but a higher prevalence of diastolic dysfunction (62.5% vs 21.1%, P < 0.001), as defined by E/A ratio < 1 and an E-wave deceleration time > 220 ms
Chiu et al[251]	United States, 2020	Cross-sectional study	2356 Framingham Heart Study participants (CT)	MASLD was associated with LV mass (β = 1.45, 95%CI: 0.01-2.88), LV wall thickness (β = 0.01, 95%CI: 0.00-0.02), mass volume ratio (β = 0.02, 95%CI: 0.01-0.03), mitral peak velocity (E) (β = 0.83, 95%CI: 0.31-1.36) and LV filling pressure (E/e’ ratio) (β = 0.16, 95%CI: 0.09-0.23); and inversely associated with global systolic longitudinal strain (β = 0.20, 95%CI: 0.07-0.33), diastolic annular velocity (e’) (β = -0.12, 95%CI: -0.22 to -0.03), and E/A ratio (β = -0.01, 95%CI: -0.02 to -0.00)
VanWagner et al[253]	United States, 2020	Large population-based prospective study	1827 participants (CT)	MASLD had higher LV mass, relative wall thickness, incident LV hypertrophy, and abnormal LV geometry vs non-MASLD (P < 0.02). MASLD had impaired LV relaxation (E/A ratio 1.1 vs 1.2), higher LV filling pressures (E/e’ ratio 7.9 vs 7.2), worse longitudinal strain (-13.9% vs -15.3%), and lower LV ejection fraction (58.9% vs 60.2%, P < 0.01)
VanWagner et al[254]	United States, 2015	Cross-sectional analysis	2713 participants (CT)	MASLD had lower early diastolic relaxation (e’) velocity (10.8 ± 2.6 cm/second vs 11.9 ± 2.8 cm/second), higher LV filling pressure (E/e’ ratio: 7.7 ± 2.6 vs 7.0 ± 2.3), and worse absolute GLS (14.2% ± 2.4% vs 15.2% ± 2.4%) than non-MASLD (P < 0.0001 for all)
Arrhythmias and conduction disorders
Cai et al[261]	China, 2020	Meta-analysis of cohort studies	6 studies; 614673 participants (ultrasonography, CT, FLI)	MASLD was associated with an increased risk of AF (RR = 1.65, 95%CI: 1.23-2.20, I2 = 63.0%). After adjustment for multiple cardiometabolic risk factors, the association was still higher than that in non-MASLD (RR = 1.19, 95%CI: 1.04-1.31, I2 = 54.0%)
Donnellan et al[262]	United States, 2020	Retrospective cohort study	267 patients (ultrasonography, CT, MRI)	MASLD was independently associated with increased rates of arrhythmia recurrence (HR = 3.01, 95%CI: 1.98-4.68, P < 0.0001)
Mantovani et al[263]	Italy, 2016	Retrospective, cross-sectional design	330 patients (ultrasonography)	MASLD was associated with a 35-fold increased risk of ventricular arrhythmias (OR = 3.47, 95%CI: 1.65-7.30)
Targher et al[264]	Italy, 2013	Prospective study	400 patients (ultrasonography)	MASLD was associated with an increased risk of incident AF (OR = 4.49, 95%CI: 1.6-12.9)
Käräjämäki et al[265]	Finland, 2015	Prospective study	958 subjects (ultrasonography)	MASLD was an independent predictor of AF (adjusted OR = 1.88, 95%CI: 1.03-3.45)
Mantovani et al[272]	Italy, 2025	Systematic review and meta-analysis)	16 retrospective cohort studies; approximately 19.5 million participants (liver biopsy, imaging techniques, blood-based scores)	MASLD was significantly associated with an increased risk of developing incident AF (HR = 1.20, 95%CI: 1.10-1.32, I2 = 92%). This risk did not appear to further increase with the severity of liver fibrosis (n = 3 studies, HR = 1.22, 95%CI: 1.18-1.26, I2 = 10%)
Roh et al[274]	South Korea, 2020	Cross-sectional analysis	334280 healthy individuals (FLI)	AF was significantly higher in subjects with higher FLIs. Adjusted HRs indicated that a higher FLI was independently associated with an increased risk for AF (HR between Q4 and Q1 = 1.35, 95%CI: 1.11-1.63)
Targher et al[277]	Italy, 2013	Cross-sectional analysis	702 patients with T2D (ultrasonography)	MASLD was associated with an increased risk of prevalent AF (OR = 3.04, 95%CI: 1.54-6.02)
Mantovani et al[278]	Italy, 2019	Meta-analysis	9 cross-sectional and longitudinal studies; 364919 individuals (ultrasonography, biopsy, FLI)	5 cross-sectional studies showed that MASLD was associated with an increased risk of prevalent AF (OR = 2.07, 95%CI: 1.38-3.10, I2 = 54.7%) 4 longitudinal studies showed that MASLD was independently associated with a 10-year increased risk of incident AF only in T2D patients (n = 1 study; HR = 4.96, 95%CI: 1.42-17.28)
Targher et al[281]	Italy, 2014	Cross-sectional analysis	400 outpatients with T2D (ultrasonography)	MASLD was associated with an increased QTc interval (OR = 2.16, 95%CI: 1.4-3.4). Adjusted OR = 2.26, 95%CI: 1.4-3.7
Hung et al[282]	Taiwan, 2015	Cross-sectional analysis	31116 participants (ultrasonography)	Mild, moderate, and severe MASLD were associated with an increased risk for QTc prolongation (OR = 1.11, 95%CI: 1.01-1.21; OR = 1.61, 95%CI: 1.36-1.9; and OR = 1.31, 95%CI: 1.16-2.24), respectively, in women, and (OR = 1.11, 95%CI: 1.01-1.21; OR = 1.39, 95%CI: 1.22-1.59; and OR = 1.87, 95%CI: 1.16-2.24), respectively, in men
Mantovani et al[283]	Italy, 2017	Single-center, retrospective design	751 patients with T2D (ultrasonography)	Patients with MASLD had a remarkably higher prevalence of any persistent heart block than those without MASLD (31.3% vs 16.7%, P < 0.001). MASLD was associated with an increased risk of prevalent heart block (adjusted OR = 3.04, 95%CI: 1.81-5.10)
Peripheral artery disease
Song et al[285]	China, 2023	Prospective cohort study	6833 participants (ultrasonography)	MASLD was associated with a higher risk of the presence of PAD (adjusted OR = 1.30, 95%CI: 1.19-1.42). MASLD at baseline was associated with a higher risk of incident PAD (adjusted HR = 1.67, 95%CI: 1.17-2.38)
Ciardullo et al[288]	Italy, 2022	Cross-sectional complex survey	3094 participants aged 40 years or older (FLI)	PAD was associated with a higher risk of all-cause (1.8, 95%CI: 1.4-2.4) and cardiovascular mortality (HR = 2.5, 95%CI: 1.5-4.3) after adjustment

CT: Computed tomography; MRI: Magnetic resonance imaging; MRS: Magnetic resonance spectroscopy; FLI: Fatty liver index; ICD: International statistical classification of diseases; T2D: Type 2 diabetes; HSI: Hepatic steatosis index; CAC: Coronary artery calcification; MASLD: Metabolic dysfunction-associated steatotic liver disease; OR: Odds ratio; CI: Confidence interval; CIMT: Carotid intima-media thickness; ba-PWV: Brachial-ankle pulse wave velocity; CVD: Cardiovascular disease; VAT: Visceral adipose tissue; BMI: Body mass index; NFS: Non-alcoholic fatty liver disease fibrosis score; CAP: Controlled attenuation parameter; AAC: Abdominal aortic calcification; HR: Hazard ratio; CVE: Cardiovascular events; RR: Relative risk; PI: Prediction interval; MI: Myocardial infarction; IS: Ischemic stroke; HF: Heart failure; AF: Atrial fibrillation; FIB-4: Fibrosis-4; CAD: Coronary artery disease; AST: Aspartate aminotransferase; CHD: Coronary heart disease; MBG: Myocardial blush grade; STR: ST-segment resolution; MACE: Major adverse cardiovascular events; AMI: Acute myocardial infarction; LF: Low frequency; HF: High frequency; SBP: Systolic blood pressure; LV: Left ventricular; LVDD: Left ventricular diastolic dysfunction; LVH: Left ventricular hypertrophy; GLS: Global longitudinal strain; QTc: Heart rate-corrected QT; PAD: Peripheral artery disease.