Quantifying Risk of Adverse Clinical Events With One Set of Vital Signs Among Primary Care Patients with Hypertension

William M Tierney; Margaret Brunt; Joseph Kesterson; Xiao-Hua Zhou; Gil L’Italien; Pablo Lapuerta

doi:10.1370/afm.76

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Table 1.

Dichotomous Univariable Predictors of Adverse Vascular Events

			Coefficients for Univariable Proportional Hazards Regression
Variable	No.	(%)	MI	CVA	MI or CVA	IHD	HF	CRI	Death
MI = myocardial infarction, CVA = stroke (cerebrovascular accident), IHD = ischemic heart disease, HF = heart failure, CRI = chronic renal insufficiency.
* P ≤.001.
† P ≤.05.
‡ P ≤.01.
Patient Characteristics
Female sex	4028	(69)	−0.368*	−0.138^†	−0.202*	−0.224^†	0.005	−0.458*	−0.319^‡
Black race	3659	(63)	−0.362*	−0.032	−0.113^†	−0.413*	−0.408	0.278^†	0.031
Smoker	1344	(23)	0.599*	0.383*	0.439*	0.100	0.340*	0.192	0.535*
Vascular events prior to index visit
Ischemic heart disease	2,209	(38)	1.402*	0.632*	0.832*	—	0.615*	0.483*	0.635*
Renal failure	1,255	(22)	0.823*	0.773*	0.773*	0.547*	0.640*	—	1.036
Heart failure	895	(15)	1.231*	0.790*	0.941*	0.742*	—	0.979*	1.307*
Myocardial infarction	814	(14)	2.009*	0.868*	1.241*	—	0.924*	0.600*	1.034*
Stroke	563	(10)	0.720*	2.472*	2.141*	0.486^‡	0.608*	0.162*	0.827*
Myocardial infarction or stroke	1,198	(21)	1.733*	1.693*	1.777*	—	0.853*	0.513*	1.094*
Active drug therapy at index visit
Diuretics	2,493	(43)	0.405*	0.785*	0.314*	0.192	0.292*	0.530*	0.417*
Aspirin	1,306	(22)	1.254*	1.174*	1.217*	0.560*	0.794*	0.568*	0.713*
Calcium channel blockers	1,867	(32)	0.698*	0.495*	0.530*	0.124	0.526*	0.548*	0.256^‡
Ace inhibitors	1,706	(29)	0.538*	0.441*	0.475*	0.265^†	0.508*	0.558*	0.499*
Nitrates	839	(14)	1.729*	0.785*	1.083*	—	0.819*	0.842*	0.020
Beta blockers	711	(12)	0.726*	0.381*	0.494*	0.166	0.338*	0.313^†	−0.149
Insulin	581	(10)	0.729*	0.502*	0.587*	0.801*	1.020*	1.739*	0.710*
Oral antidiabetic drugs	565	(10)	0.541*	0.454*	0.488*	0.394^‡	0.515*	0.884*	0.195
Statin antilipemic drug	216	(4)	0.908*	0.600*	0.622*	0.623^†	0.476^‡	0.657^‡	0.613^‡
Alpha blockers	147	(2)	0.305	0.422^‡	0.298	0.366	0.569^‡	0.944*	0.380
Warfarin	127	(2)	1.483*	0.796*	1.040*	1.050^‡	0.939*	0.724^†	1.108*
Previous diagnoses recorded on or before index visit
Diabetes mellitus	1,933	(33)	0.899*	0.648*	0.713*	0.625*	0.788*	1.346*	0.861*
Obesity	1,508	(26)	0.090	0.029	0.058	0.032	0.258^‡	0.385*	0.010
Alcohol abuse	741	(13)	0.263^†	0.328*	0.286*	0.177	0.065	0.413^‡	0.545*
Chronic obstructive lung disease	573	(10)	0.885*	0.724*	0.796*	0.573*	0.783*	0.337	1.058*
Renal insufficiency	369	(6)	1.042*	1.060*	1.050*	0.514^†	0.778*	3.075*	1.496*
Hypothyroidism	368	(6)	0.566*	0.397*	0.418*	0.050	0.298^†	0.296	0.187
Peripheral arterial disease	257	(4)	0.998*	0.768*	0.811*	0.960*	0.703*	1.084*	1.211*

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Table 2.

Continuous Univariable Predictors of Adverse Vascular Events

			Coefficients for Univariable Proportional Hazards Regression
Variable	Mean	(SD)	MI	CVA	MI or CVA	IHD	HF	CRI	Death
MI = myocardial infarction, CVA = stroke (cerebrovascular accident), IHD = ischemic heart disease, HF = heart failure, CRI = chronic renal insufficiency.
* P ≤.001.
† P ≤.05.
‡ P ≤ 0.01.
Patient characteristics at index visit
Index age (y)	57	(14)	0.023*	0.044*	0.038*	0.021*	0.030*	0.028*	0.053*
Time treated for hypertension (y)	5.6	(5.6)	0.038*	0.057*	0.051*	0.023^†	0.041*	0.034*	0.053*
Vital signs from the index visit
Systolic blood pressure (mmHg)	143	(22)	0.001	0.007*	0.006*	0.005^†	0.009*	0.010*	0.002
Diastolic blood pressure (mmHg)	84	(13)	−0.011^‡	−0.006^†	−0.008*	−0.005	−0.001	−0 .003	−0.020*
Heart rate (beats/min)	81	(10)	−0.003	0.00043	−0.00086	0.000055	0.012^‡	0.011	0.016^‡
Mean blood pressure (mmHg)	104	(14)	−0.005	0.003	0.002	0.002	0.007^‡	0.007	−0.010^‡
Systolic blood pressure × heart rate	11,557	(2,343)	−0.000001	0.000048*	0.000034^‡	0.000036	0.000095*	0.000087*	0.000039
Pulse pressure (mmHg)	59	(18)	0.007^‡	0.013*	0.012*	0.010*	0.013*	0.016*	0.012*
Pulse pressure × heart rate	4,770	(1,594)	0.000006^†	0.00012*	0.00011*	0.00011*	0.00016*	0.00016*	0.00013*
Height (in)	65	(3)	0.027^†	−0.009	−0.003	0.014	0.005	0.026	0.017
Weight (lb)	192	(52)	−0.003^‡	−0.006*	−0.005*	−0.001	0.00053	0.001	−0.006*
Body mass index	32	(8)	−0.020^‡	−0.035*	−0.032*	−0.007	0.005	0.003	−0.037*
Laboratory test results available at index visit
Hemoglobin (g/dL) (n = 5,248)	13.4	(1.6)	−0.040	−0.046^†	−0.047^‡	0.002	−0.074^‡	−0.138*	-0.168*
Creatinine (mg/dL) (n = 5,487)	1.1	(0.6)	0.289*	0.245*	0.252*	0.235*	0.258*	3.540*	0.382*
Cholesterol (mg/dL) (n = 5,248)	210	(47)	0.003^‡	0.002*	0.002*	0.003^‡	0.002^‡	0.001	−5.8 3 10⁻⁴
Albumin (g/dL) (n = 5,157)	4.1	(0.4)	−0.571*	−0.411*	−0.446*	−0.388^‡	−0.693*	−1.087*	−1.066*
Uric acid (mg/dL) (n = 5,172)	5.9	(1.7)	0.100*	0.075*	0.074*	0.075^‡	0.093*	0.207*	0.126*
Glucose (mg/dL) (n = 5,475)	126	(63)	0.003*	0.002*	0.002*	0.003*	0.003*	0.005*	0.003*
Potassium (mEq/L) (n = 5,267)	4.1	(0.4)	0.361*	0.349*	0.335*	0.123	0.163	0.054*	0.404*

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Table 3.

Multivariable Models With Vital Signs Predicting Adverse Vascular Events

Outcome Predicted (Subjects)	Vital Sign	PValue	Risk Ratio (95% CI)	Other Significant Multivariable Predictors*
CI = 95% confidence interval.
* From information available on or before index visit. See text for definitions. Variables are listed in decreasing order of predictive power. Those variables underlined were negatively correlated with risk of the outcome event.
Myocardial infarction (all patients)	None			Previous myocardial infarction, smoker, nitrates, warfarin, diabetes, time treated for hypertension, renal insufficiency, aspirin
First myocardial infarction (patients with no previous infarction)	Systolic blood pressure	.016	1.010 (1.002–1.018)	Calcium channel blocker, diabetes, uric acid, African American
Stroke (all patients)	Systolic blood pressure	.001	1.007 (1.003–1.011)	Prior stroke, age, weight, aspirin, calcium channel blocker, chronic obstructive pulmonary disease, uric acid, diabetes, renal insufficiency, glucose, previous myocardial infarction or stroke, creatinine clearance (calculated)
First stroke (patients with no previous stroke)	Diastolic blood pressure	.005	1.013 (1.004–1.023)	Age, weight, aspirin, chronic obstructive pulmonary disease, diabetes, heart failure, uric acid, creatinine, creatinine clearance (calculated), glucose, renal insufficiency
Myocardial infarction or stroke (all patients)	Systolic blood pressure	.0015	1.006 (1.002–1.009)	Previous stroke, previous stroke or myocardial infarction, age, aspirin, renal insufficiency, diabetes, smoker, weight, time treated for hypertension, nitrates, chronic obstructive pulmonary disease, glucose
First myocardial infarction or stroke (patients with no previous myocardial infarction or stroke)	Systolic blood pressure	.005	1.007 (1.002–1.012)	Age, smoker, chronic obstructive pulmonary disease, diabetes, uric acid, body mass index, renal insufficiency, glucose, warfarin
Ischemic heart disease (patients with no previous ischemic heart disease)	Systolic blood pressure	.005	1.009 (1.003–1.015)	Insulin, heart failure, age, oral hypoglycemic drug, African American, peripheral arterial disease
Heart failure (patients with no prior heart failure)	Mean blood pressure	.001	1.012 (1.005–1.020)	Age, albumin, insulin, uric acid, chronic obstructive pulmonary disease, previous myocardial infarction, oral hypoglycemic drug, cholesterol, obesity, calcium channel blocker
Chronic renal Insufficiency (patients with no prior chronic renal insufficiency)	Systolic blood pressure	<.001	1.013 (1.006 – 1.021)	Creatinine, insulin, albumin, oral hypoglycemic drug, heart failure, glucose, acute renal failure, alcoholism, calcium channel blocker, hemoglobin, peripheral arterial disease
All-cause mortality	Heart rate	.003	1.016 (1.005–1.026)	Age, albumin, heart failure, alcoholism glucose, peripheral arterial disease, renal insufficiency, creatinine, smoker, time treated for hypertension, previous stroke or myocardial infarction, statin antilipemic drug, chronic obstructive pulmonary disease

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Table 4.

Model Performance in the Validation Cohort

Outcome Predicted (Subjects)	Number of Patients	Patient With Outcome No. (%)	C-Statistic
* Good predictive model (defined a priori as having a C -statistic > 0.70)^39,⁴⁰
Myocardial infarction (all patients)	2,912	198 (6.8)	0.76*
First myocardial infarction (patients with no previous myocardial infarction)	2,522	112 (4.4)	0.62
Stroke (all patients)	2,912	514 (18)	0.79*
First stroke (patients with no previous stroke)	2,612	317 (12)	0.67
Myocardial infarction or stroke (all patients)	2,912	640 (22)	0.78*
First myocardial infarction or stroke (patients with no previous myocardial infarction or stroke)	2,326	334 (14)	0.65
First ischemic heart disease (patients with no previous ischemic heart disease)	1,811	194 (11)	0.63
First heart failure (patients with no previous heart failure)	2,481	332 (13)	0.68
First chronic renal insufficiency (patients with no previous renal insufficiency)	2,281	151 (6.6)	0.81*
All-cause mortality (all patients)	2,912	378 (13)	0.78*

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Table 5.

Marginal Predictive Power of the Significant Vital Sign

Outcome Predicted	Partial Likelihood Ratio Statistic	PValue
First myocardial infarction (patients with no previous myocardial infarction)	5.55	.0180
Stroke (all patients)	10.32	.0013
First stroke (patients with no previous stroke)	7.78	.0053
Myocardial infarction or stroke (all patients)	6.28	.0120
First myocardial infarction or stroke (patients with no previous myocardial infarction or stroke)	7.66	.0065
First ischemic heart disease (patients with no previous ischemic heart disease)	7.76	.0053
First heart failure (patients with no previous heart failure)	9.99	.0016
First chronic renal insufficiency (patients with no previous renal insufficiency)	13.38	.0002
All-cause mortality (all patients)	8.65	.0033

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The Article in Brief

A blood pressure reading includes two numbers: systolic blood pressure (the first number), which is measured after a heart beat, and diastolic blood pressure (the second number), which is measured between heart beats. A single finding of high systolic blood pressure can be a sign of increased risk of stroke, heart disease, heart attack, or kidney failure.