Biostatistics Case Studies


CASE 7: Clinical Significance


Clinical History:

A 44-year-old African-American man has a long history of poorly controlled hypertension, generally in the range of 145/95 mm Hg.

His blood pressure 5 years later is 160/105 mm Hg. His BUN is currently 45 mg/dl and serum creatinine 3.5 mg/dl. His hemoglobin A1C is 9.5%.

  1. Describe the changes seen in this high magnification microscopic image of a renal glomerulus.

    2. The glomerulus demonstrates an area of amorphous deposition of PAS-positive material typical for nodular glomerulosclerosis (Kimmelstiel-Wilson lesion) and the arteriole at the base of the glomerulus shows extensive thickening consistent with hyaline arteriolosclerosis.

  2. What underlying disease process is probably present?

    3. These changes are typical for diabetes mellitus.

Further History:

Today he has a severe headache, and on arrival in the emergency room his blood pressure is recorded as 220/150 mg Hg.

  1. What is the nature of the process seen in the renal artery shown here microscopically at high magnification?

    2. This is hyperplastic arteriolosclerosis in which there is lumenal narrowing with prominent intimal proliferation ("onion-skinning"). This lesion is most likely to accompany hypertensive emergency (malignant hypertension) when systolic pressure is ≥180 and/or diastolic pressure ≥120 mmHg along with signs of acute or ongoing end-organ damage, which complicates about 1% of cases of "essential" or "benign" hypertension, is more common in men.

  2. What complications are likely to develop?

    3. He could develop renal failure, cerebral hemorrhage (stroke), or congestive heart failure.

  3. Describe two mechanisms by which renal artery ischemia produces hypertension.

    4. Renal ischemia triggers the release of renin from the juxtaglomerular apparatus. Renin is converted ultimately to angiotensin II which has a direct vasoconstrictor effect as well as a stimulatory effect on the release of aldosterone. The combined salt and water retention triggered by aldosterone and the vasoconstriction lead to renal hypertension. This was originally described by Goldblatt and is often referred to as "Goldblatt hypertension."

Statistical Review:

Clinical studies are performed comparing treatment regimens to lower blood pressure in patients with stage 2 hypertension (160-179/100-109 mm Hg). In the chart below, the reduction in diastolic blood pressure (in mm Hg) is given with 95% confidence intervals for each study. Study A consists of patients who went on a low salt diet along with a regular exercise regimen for 3 months. Study B consists of patients who took two drugs. Study C consists of patients who took one drug. Study D consists of patients who took no drugs and made no lifestyle modifications. The "range of clinical indifference" is marked by the yellow bar.

Question:

  1. What do the confidence intervals indicate for these four regimens?

    2. Study A has confidence intervals that are above the "null" value of no change in diastolic blood pressure, but overlapping the range of clinical indifference (the range over which you would not choose to do anything differently). It is above the "null" value and, hence, has statistical significance, but most of the range lies within the clinical indifference zone, so there may be no practical significance. Perhaps, a larger study population would show practical significance to this regimen.

    Study B does not overlap the "null" value and is entirely above the range of clinical indifference, so it has results that are of clinical and practical significance.

    Study C overlaps the "null" value and the results probably have no clinical significance, but a larger study might show significance.

    Study D overlaps the "null" value and is entirely within the range of clinical indifference, so it has no significance.