We observed differences in hypertension control by race and sex within the KEEP sample, particularly in patients with early CKD. These differences correspond to disparities in the risk of progression from CKD to ESRD. African American men are at the greatest risk of CKD progression and have higher blood pressure values than other race/sex groups. Because adequate hypertension control may be the single most important intervention available at this time to slow the progression of renal disease,16
our findings emphasize the particular need to screen for, diagnose, and aggressively treat hypertension in African American men with CKD.
There are several potential explanations for the increased blood pressure values we observed in African American men with CKD. First, differences in blood pressure between African American men and women with CKD may be in part biological because both human and animal studies indicated that sex hormones have a role in vascular reactivity. Estrogens may upregulate production of such vasorelaxant substances as nitric oxide, react directly on vascular smooth muscle cells, and dampen the cardiovascular stress response to adrenergic stimuli.17–19
Conversely, testosterone was shown to increase secretion of such vasoconstrictors as endothelin and stimulates the renin-angiotensin-aldosterone system, leading to inadequate sodium excretion in the setting of increased arterial blood pressure.18,19
Genetic variability related to the renin-angiotensin-aldosterone system and/or the α
-adrenergic receptor also was linked in population-based studies to sex differences in blood pressure in both African Americans20
However, a primary biological explanation for sex differences in hypertension control would suggest persistently increased blood pressures for both African American and white men relative to women. Although this was true in the past,17
recent data showed a different pattern and suggested a second potential explanation for our findings; specifically, that the race/sex disparity we observed is caused largely by differences in treatment rates. Analyses of the 1999–2000 National Health and Nutrition Examination Survey (NHANES) indicate that a sex disparity in hypertension control persists for African Americans, but white men now have equivalent or better hypertension control than white women because of increasing treatment rates over time.22,23
Our findings therefore support the need for additional analyses, including studies with data for the frequency and intensity of antihypertensive therapy, to determine the cause of poor hypertension control in African American men with early-and late-stage CKD.
A third potential explanation for our findings of poor hypertension control for African American men with CKD is variations in access to and use of health care in individuals receiving antihypertensive treatment. In African Americans with hypertension, some data indicate that men are less likely to have health insurance, more likely to receive care in a public clinic, and less likely to have regular physician visits than women regardless of socioeconomic status.24
The lack of insurance in the NHANES III cohort was associated with lower rates of blood pressure control in treated patients with hypertension, but had no effect on blood pressure control in untreated persons with hypertension.25
The majority of African Americans who participated in KEEP had adequate access to health care because more than 80% had health insurance and more than 85% had a regular physician.26
However, men were less likely than women to have either insurance or an identified physician, suggesting that sex-based differences in access could contribute to suboptimal medication regimens and poor hypertension control in men.
The NKF issued practice guidelines emphasizing that interventions to improve hypertension control and slow the progression of kidney disease must begin during early CKD, specifically stages 1 and 2, which are characterized by microalbuminuria, but maintained glomerular filtration rate.27
Within our sample, African Americans were more likely than whites to have stage 1 or 2 CKD versus stage 3 CKD, consistent with published NHANES III data.28
African Americans with CKD were also younger than whites. This earlier-onset hypertension may present an increased risk of decreases in renal function starting at a younger age. Our findings indicate missed opportunities to prevent ESRD in a relatively young and high-risk population. Aggressive hypertension treatment of all persons with early CKD, delivered mainly by primary care providers, may decrease both the race and sex disparities in progression from CKD to ESRD.
We observed race and sex disparities in both systolic and diastolic blood pressure values, but the magnitude of differences was greater for diastolic blood pressures. The preponderance of evidence suggests that systolic blood pressure, rather than diastolic blood pressure, is the primary determinant of CKD progression.8,29
However, data from the MDRD trial indicate that controlling mean arterial pressure, which is primarily determined by diastolic blood pressure, slows CKD progression in persons without diabetes.30
The MDRD intervention group achieved a mean arterial pressure of 5.1 mm Hg less than in the control group, with a corresponding hazard ratio of 0.68 for the development of ESRD at 6 years of follow-up. Current guidelines for hypertension control in patients with CKD recommend systolic blood pressure less than 130 mm Hg along with diastolic blood pressure less than 80 mm Hg to prevent progression of renal disease and associated cardiovascular complications.31
Our study has several limitations. We did not have access to medical records or information for antihypertensive medication regimens and classified participants as hypertensive based on self-report. We used 2 blood pressure measurements on a single day to evaluate hypertension control. The predictive value of this approach should not vary by participant race or sex and therefore should not introduce directional bias into our analyses. We did not have information about quantity of microalbuminuria and are unable to comment on the relationship between severity of microalbuminuria and poor hypertension control. Also, KEEP was a targeted screening of individuals at risk of CKD and therefore is not representative of the general population of the United States. Persons who participate in such screening programs tend to be those who are more concerned about their health. In addition, KEEP enrolled large numbers of participants in the southeastern United States, a region with low rates of hypertension control for both African Americans and whites.32
In conclusion, we found that in hypertensive patients in a community-based screening of patients at risk of CKD, blood pressure values varied by both race and sex, with African American men at greatest risk of inadequate hypertension control compared with whites, followed by African American women at intermediate risk. These race and sex disparities in hypertension control correspond to those at risk of rapid progression from CKD to ESRD and suggest the importance of improved hypertension control in early CKD for African American men in particular. However, these results require confirmation in population-based cohorts with more complete data for medication and health care use.