United States Medical Licensing
Examination Step One – Comprehensive
Medical Knowledge Assessment Version
3.1 – Advanced Clinical Integration &
Foundational Science Examination
Examination Format: 150 Multiple-Choice Questions (Single Best Answer)
Target Audience: Medical Students Preparing for USMLE Step 1
Difficulty Level: Advanced / Complex (integrating multiple foundational science disciplines with
clinical presentation)
Time Allotment: 3 hours 45 minutes (150 minutes)
SECTION 1: CARDIOVASCULAR SYSTEM – ADVANCED INTEGRATION
Question 1
A 62-year-old African American man with a 30-year history of hypertension presents with
progressive exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea.
Echocardiography reveals concentric left ventricular hypertrophy with an ejection fraction of
65%. He has been adherent to his antihypertensive regimen of lisinopril and
hydrochlorothiazide but his blood pressure remains 158/92 mmHg. Physical examination reveals
an S4 gallop, jugular venous distention, and bilateral crackles at the lung bases. Which of the
following additional medications would most likely improve his mortality and reduce
hospitalizations?
A) Spironolactone
B) Amlodipine
C) Doxazosin
,D) Atenolol
E) Clonidine
Correct Answer: A) Spironolactone
Rationale: This patient has heart failure with preserved ejection fraction (HFpEF) with resistant
hypertension. The TOPCAT trial demonstrated that spironolactone reduces hospitalizations in
HFpEF. Amlodipine (B) is a calcium channel blocker that may worsen edema. Doxazosin (C) is an
alpha-blocker associated with increased heart failure risk in ALLHAT. Atenolol (D) is a beta-
blocker not preferred as initial therapy in HFpEF. Clonidine (E) is a centrally acting agent with
significant side effects.
Question 2
A 28-year-old gravida 2 para 0 woman at 34 weeks gestation presents with a blood pressure of
165/105 mmHg and 3+ proteinuria on a 24-hour urine collection. She reports a severe frontal
headache, blurred vision, and epigastric pain. Laboratory studies reveal platelet count of
78,000/μL, AST of 120 U/L, ALT of 95 U/L, and haptoglobin of 15 mg/dL. Which of the following
is the most appropriate next step in management?
A) Oral labetalol 200 mg twice daily
B) Intravenous magnesium sulfate bolus followed by continuous infusion
C) Emergent cesarean delivery
D) Intravenous hydralazine 10 mg
E) Methylprednisolone 1 g intravenous
Correct Answer: B) Intravenous magnesium sulfate bolus followed by continuous infusion
Rationale: This patient has HELLP syndrome (hemolysis, elevated liver enzymes, low platelets)
superimposed on preeclampsia. Magnesium sulfate is indicated for seizure prophylaxis
regardless of neurologic symptoms. While antihypertensives (A, D) may be needed for blood
pressure control, magnesium sulfate addresses the risk of eclampsia. Emergent delivery (C) is
indicated for HELLP syndrome but after magnesium sulfate administration. Methylprednisolone
(E) is used for refractory cases but magnesium sulfate is the priority.
Question 3
A 55-year-old man with a history of coronary artery disease and a drug-eluting stent placed 9
months ago presents with acute substernal chest pain radiating to his left arm. ECG shows ST-
segment elevation in leads V1-V4. He is given aspirin, heparin, and ticagrelor. Emergent
,coronary angiography reveals a 95% in-stent restenosis of the proximal left anterior descending
artery. Which of the following mechanisms is most likely responsible for this restenosis?
A) Neointimal hyperplasia due to smooth muscle cell proliferation
B) Thrombus formation from stent malapposition
C) Allergic reaction to the polymer coating
D) Endothelial dysfunction from radiation therapy
E) Fibrocalcific plaque progression distal to the stent
Correct Answer: A) Neointimal hyperplasia due to smooth muscle cell proliferation
Rationale: Drug-eluting stents reduce restenosis compared to bare-metal stents, but neointimal
hyperplasia from smooth muscle cell proliferation can still occur. Thrombus formation (B) is
more common in the first months after stenting. Allergic reactions to the polymer (C) are rare.
Radiation therapy (D) is used for in-stent restenosis but is not a cause. Plaque progression (E) is
less likely.
Question 4
A 72-year-old woman with severe aortic stenosis presents with progressive dyspnea, angina,
and syncope on exertion. Echocardiography shows a peak aortic valve gradient of 70 mmHg and
an aortic valve area of 0.6 cm². She has a history of coronary artery disease and chronic kidney
disease stage 3. Which of the following is the most appropriate management?
A) Surgical aortic valve replacement with a bioprosthetic valve
B) Transcatheter aortic valve replacement
C) Medical management with digoxin and furosemide
D) Balloon aortic valvuloplasty
E) Percutaneous coronary intervention followed by aortic valve surgery
Correct Answer: B) Transcatheter aortic valve replacement
Rationale: This patient with severe aortic stenosis and multiple comorbidities is at high surgical
risk. TAVR is preferred over surgical AVR (A) in high-risk patients. Medical management (C)
provides only symptomatic relief and does not alter prognosis. Balloon valvuloplasty (D) is a
bridge to definitive therapy in unstable patients. PCI (E) may be needed but TAVR is the primary
definitive therapy.
Question 5
A 48-year-old woman presents with palpitations, diaphoresis, and tremors. During the episode,
, her blood pressure is 210/110 mmHg and heart rate is 120 bpm. She reports a history of similar
episodes triggered by laughter and bending over. Between episodes, her blood pressure is
120/80 mmHg. Laboratory studies reveal elevated plasma metanephrines. Which of the
following is the most appropriate next step in localization?
A) Adrenal CT with contrast
B) MIBG scintigraphy
C) 18F-FDG PET/CT
D) MRI of the abdomen
E) Somatostatin receptor scintigraphy
Correct Answer: A) Adrenal CT with contrast
Rationale: Pheochromocytoma is diagnosed by elevated plasma metanephrines. Adrenal CT is
the first-line localization study as 90% of pheochromocytomas are in the adrenal medulla. MIBG
(B) and PET/CT (C) are used for metastatic or extra-adrenal disease. MRI (D) is an alternative but
CT is preferred. Somatostatin receptor scintigraphy (E) is used for neuroendocrine tumors.
Question 6
A 65-year-old man with hypertension and diabetes presents with a 2-month history of
progressive lower extremity edema and foamy urine. Laboratory studies reveal serum creatinine
1.8 mg/dL, albumin 2.5 g/dL, and 24-hour urine protein of 6.2 g. Renal biopsy shows
eosinophilic, amorphous, Congo red-positive deposits in the glomerular basement membrane.
Which of the following is the most likely diagnosis?
A) Diabetic nephropathy
B) Amyloidosis
C) Membranous nephropathy
D) Focal segmental glomerulosclerosis
E) Minimal change disease
Correct Answer: B) Amyloidosis
Rationale: Congo red-positive deposits with apple-green birefringence under polarized light are
diagnostic of amyloidosis. Diabetic nephropathy (A) shows mesangial expansion and
Kimmelstiel-Wilson nodules. Membranous nephropathy (C) shows subepithelial spikes. FSGS (D)
shows segmental sclerosis. Minimal change disease (E) shows foot process effacement.
Examination Step One – Comprehensive
Medical Knowledge Assessment Version
3.1 – Advanced Clinical Integration &
Foundational Science Examination
Examination Format: 150 Multiple-Choice Questions (Single Best Answer)
Target Audience: Medical Students Preparing for USMLE Step 1
Difficulty Level: Advanced / Complex (integrating multiple foundational science disciplines with
clinical presentation)
Time Allotment: 3 hours 45 minutes (150 minutes)
SECTION 1: CARDIOVASCULAR SYSTEM – ADVANCED INTEGRATION
Question 1
A 62-year-old African American man with a 30-year history of hypertension presents with
progressive exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea.
Echocardiography reveals concentric left ventricular hypertrophy with an ejection fraction of
65%. He has been adherent to his antihypertensive regimen of lisinopril and
hydrochlorothiazide but his blood pressure remains 158/92 mmHg. Physical examination reveals
an S4 gallop, jugular venous distention, and bilateral crackles at the lung bases. Which of the
following additional medications would most likely improve his mortality and reduce
hospitalizations?
A) Spironolactone
B) Amlodipine
C) Doxazosin
,D) Atenolol
E) Clonidine
Correct Answer: A) Spironolactone
Rationale: This patient has heart failure with preserved ejection fraction (HFpEF) with resistant
hypertension. The TOPCAT trial demonstrated that spironolactone reduces hospitalizations in
HFpEF. Amlodipine (B) is a calcium channel blocker that may worsen edema. Doxazosin (C) is an
alpha-blocker associated with increased heart failure risk in ALLHAT. Atenolol (D) is a beta-
blocker not preferred as initial therapy in HFpEF. Clonidine (E) is a centrally acting agent with
significant side effects.
Question 2
A 28-year-old gravida 2 para 0 woman at 34 weeks gestation presents with a blood pressure of
165/105 mmHg and 3+ proteinuria on a 24-hour urine collection. She reports a severe frontal
headache, blurred vision, and epigastric pain. Laboratory studies reveal platelet count of
78,000/μL, AST of 120 U/L, ALT of 95 U/L, and haptoglobin of 15 mg/dL. Which of the following
is the most appropriate next step in management?
A) Oral labetalol 200 mg twice daily
B) Intravenous magnesium sulfate bolus followed by continuous infusion
C) Emergent cesarean delivery
D) Intravenous hydralazine 10 mg
E) Methylprednisolone 1 g intravenous
Correct Answer: B) Intravenous magnesium sulfate bolus followed by continuous infusion
Rationale: This patient has HELLP syndrome (hemolysis, elevated liver enzymes, low platelets)
superimposed on preeclampsia. Magnesium sulfate is indicated for seizure prophylaxis
regardless of neurologic symptoms. While antihypertensives (A, D) may be needed for blood
pressure control, magnesium sulfate addresses the risk of eclampsia. Emergent delivery (C) is
indicated for HELLP syndrome but after magnesium sulfate administration. Methylprednisolone
(E) is used for refractory cases but magnesium sulfate is the priority.
Question 3
A 55-year-old man with a history of coronary artery disease and a drug-eluting stent placed 9
months ago presents with acute substernal chest pain radiating to his left arm. ECG shows ST-
segment elevation in leads V1-V4. He is given aspirin, heparin, and ticagrelor. Emergent
,coronary angiography reveals a 95% in-stent restenosis of the proximal left anterior descending
artery. Which of the following mechanisms is most likely responsible for this restenosis?
A) Neointimal hyperplasia due to smooth muscle cell proliferation
B) Thrombus formation from stent malapposition
C) Allergic reaction to the polymer coating
D) Endothelial dysfunction from radiation therapy
E) Fibrocalcific plaque progression distal to the stent
Correct Answer: A) Neointimal hyperplasia due to smooth muscle cell proliferation
Rationale: Drug-eluting stents reduce restenosis compared to bare-metal stents, but neointimal
hyperplasia from smooth muscle cell proliferation can still occur. Thrombus formation (B) is
more common in the first months after stenting. Allergic reactions to the polymer (C) are rare.
Radiation therapy (D) is used for in-stent restenosis but is not a cause. Plaque progression (E) is
less likely.
Question 4
A 72-year-old woman with severe aortic stenosis presents with progressive dyspnea, angina,
and syncope on exertion. Echocardiography shows a peak aortic valve gradient of 70 mmHg and
an aortic valve area of 0.6 cm². She has a history of coronary artery disease and chronic kidney
disease stage 3. Which of the following is the most appropriate management?
A) Surgical aortic valve replacement with a bioprosthetic valve
B) Transcatheter aortic valve replacement
C) Medical management with digoxin and furosemide
D) Balloon aortic valvuloplasty
E) Percutaneous coronary intervention followed by aortic valve surgery
Correct Answer: B) Transcatheter aortic valve replacement
Rationale: This patient with severe aortic stenosis and multiple comorbidities is at high surgical
risk. TAVR is preferred over surgical AVR (A) in high-risk patients. Medical management (C)
provides only symptomatic relief and does not alter prognosis. Balloon valvuloplasty (D) is a
bridge to definitive therapy in unstable patients. PCI (E) may be needed but TAVR is the primary
definitive therapy.
Question 5
A 48-year-old woman presents with palpitations, diaphoresis, and tremors. During the episode,
, her blood pressure is 210/110 mmHg and heart rate is 120 bpm. She reports a history of similar
episodes triggered by laughter and bending over. Between episodes, her blood pressure is
120/80 mmHg. Laboratory studies reveal elevated plasma metanephrines. Which of the
following is the most appropriate next step in localization?
A) Adrenal CT with contrast
B) MIBG scintigraphy
C) 18F-FDG PET/CT
D) MRI of the abdomen
E) Somatostatin receptor scintigraphy
Correct Answer: A) Adrenal CT with contrast
Rationale: Pheochromocytoma is diagnosed by elevated plasma metanephrines. Adrenal CT is
the first-line localization study as 90% of pheochromocytomas are in the adrenal medulla. MIBG
(B) and PET/CT (C) are used for metastatic or extra-adrenal disease. MRI (D) is an alternative but
CT is preferred. Somatostatin receptor scintigraphy (E) is used for neuroendocrine tumors.
Question 6
A 65-year-old man with hypertension and diabetes presents with a 2-month history of
progressive lower extremity edema and foamy urine. Laboratory studies reveal serum creatinine
1.8 mg/dL, albumin 2.5 g/dL, and 24-hour urine protein of 6.2 g. Renal biopsy shows
eosinophilic, amorphous, Congo red-positive deposits in the glomerular basement membrane.
Which of the following is the most likely diagnosis?
A) Diabetic nephropathy
B) Amyloidosis
C) Membranous nephropathy
D) Focal segmental glomerulosclerosis
E) Minimal change disease
Correct Answer: B) Amyloidosis
Rationale: Congo red-positive deposits with apple-green birefringence under polarized light are
diagnostic of amyloidosis. Diabetic nephropathy (A) shows mesangial expansion and
Kimmelstiel-Wilson nodules. Membranous nephropathy (C) shows subepithelial spikes. FSGS (D)
shows segmental sclerosis. Minimal change disease (E) shows foot process effacement.
