From a total of 5,888 CHS participants, 2,146 reported a history of hypertension. During the first follow-up period, 12% reported being on no antihypertensives, and 88% reported being on an average of 1 or more antihypertensives (). Persons on antihypertensives were of similar age and had a similar prevalence of smoking as persons on no antihypertensive medications; but were more likely to be female, self-identify as black race, have less education, and have lower income compared with persons on no antihypertensive medications. In addition, persons on antihypertensives were less likely to drink alcohol, had higher BMI, cholesterol, triglycerides, and C-reactive protein levels. Blood pressure levels, LDL-cholesterol, cognitive function and the prevalence of frailty were similar in persons on any or no antihypertensive medications. Persons on antihypertensive therapy were more likely to have diabetes, cardiovascular disease, heart failure, and disability at baseline.
Baseline characteristics of participants in the Cardiovascular Health Study (1989–1990 or 1992–1993, U.S.)
A total of 1,576 participants had cystatin C measured at two or more visits. The mean annual increase in cystatin C in these participants was 0.035 ± 0.074 mg/L (mean ± standard deviation), which corresponds to a decrease in eGFR of 2.41 ± 4.91 mL/min/1.73 m2 (). The distribution of annual change in eGFR appeared slightly left skewed.
Distribution of Annual Change in eGFR in Hypertensive Participants in the Cardiovascular Health Study (1989 – 1997, U.S.)
In unadjusted analysis, antihypertensive medication use was not associated with a change in kidney function (). Traditional multivariable adjustment for demographics, risk factors, blood pressure, cardiovascular disease, and heart failure did not substantially alter the point estimates for the association of antihypertensive medication use with decline in kidney function.
Antihypertensive medication use and change in kidney function in the Cardiovascular Health Study (1989 – 1997, U.S.)
Based on a marginal structural model with IPTW to account for the time-independent and time-dependent confounding, the estimate was modestly further in the protective direction, although did not reach statistical significance (). Based on a marginal structural model with the IPTW-reduced targeted MLE, the point estimates of effect of antihypertensive medication use was a 0.88 mL/min/1.73m2 slower decline in kidney function (p=0.02), compared to persons on no medications (). This estimate was larger in magnitude and had a smaller coefficient of variation compared with those obtained using traditional multivariable regression or IPTW-alone ()
Antihypertensive Medication Use and Change in Kidney Function in the Cardiovascular Health Study (1989 – 1997, U.S.), Based on Traditional and Marginal Structural Model Analysis
Accounting for the informative censoring had a substantial effect on the estimates; the mean estimate of effect for antihypertensive medications use was 1.38 mL/min/1.73m2 (p=0.15) slower decline in eGFR based on IPTW/IPCW alone (); and 2.23 mL/min/1.73m2 (p=0.06), based on the IPTW/IPCW-reduced targeted MLE. Variables associated with censoring were indicators of poor health status: age, lower income, smoking, worse cognitive function, worse kidney function, higher LDL-cholesterol, diabetes, heart failure, frailty, antihypertensive medication use.
There was no evidence for violation of the experimental treatment assignment assumption based on the distribution of weights across the exposure groups. The maximum for the treatment weights was 2.09 at follow-up period one and 1.91 follow-up period two (). The maximum for the censoring weights was 5.40 at follow-up period one and 6.38 at follow-up period two. All weights were had a mean value of 1.00 ().
Distribution of Inverse Probability Weights