Intentional Weight Loss and Dose Reductions of Antihypertensive Medications: A Retrospective Cohort StudyShantha G.P.S.a, g · Kumar A.A.a · Kahan S.b, f · Cheah S.Y.d · Cheskin L.J.c–e
Departments of aEpidemiology, bHealth Policy and Management and cHealth, Behavior and Society, and dDepartment of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, and eJohns Hopkins Weight Management Center, Johns Hopkins University, Baltimore, Md., fDepartment of Health Policy, George Washington University School of Public Health and Health Services, Washington, D.C., and gThe Wright Center for Graduate Medical Education, Scranton, Pa., USA Corresponding Author
Background: Though it is well known that weight loss tends to decrease blood pressure, the quantitative association between the magnitude of weight loss and the effect on the need for antihypertensive medications is not well studied. We analyzed this association among overweight and obese attendees at two outpatient weight management centers. Methods: Case records of patients with a body mass index >25 at baseline were analyzed. The weight loss intervention consisted of a calorie-restricted diet (~1,000 kcal/day deficit), a behavior modification plan, and a plan for increasing physical activity. Results: The study cohort consisted of 100 participants, and the mean follow-up period was 15 ± 3.5 months. Significant weight loss (12.2 ± 3.4 kg) and systolic/diastolic blood pressure reductions (9.1/6.3 mm Hg) were observed by study exit. For 5, 10, and 15% weight loss, respectively, 3, 39, and 39% of the patients achieved at least 1 discontinuation of any antihypertensive medication, and 8, 42, and 21 dose reductions were achieved. Dose reductions or discontinuations occurred in all classes of antihypertensive medications with similar magnitudes of weight loss. Conclusions: Intentional weight loss can potentially result in dose reductions/discontinuations of antihypertensive medications. Our results should be validated with data from larger randomized controlled studies and may help to inform the conduct of a systematic review of prior randomized controlled trials that contain data on medication changes accompanying weight loss.
© 2013 S. Karger AG, Basel
The National Health and Nutrition Examination Survey (NHANES) has shown that, in the last decade, 35% of adult Americans were obese [body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) ≥30], and that the prevalence is expected to increase in the years to come . Hypertension is common in obese individuals . For every 10-kg increase in body weight, mean systolic and diastolic blood pressures (SPB and DPB) have been found to be increased by 3 and 2 mm Hg, respectively . Furthermore, adults who are +20% overweight have an eight-fold greater incidence of hypertension . Antihypertensive medications, though known to significantly decrease morbidity and mortality among individuals with hypertension [5,6,7], are costly and often accompanied by side effects.
The good news is that intentional weight loss significantly decreases both SPB and DBP [8,9,10]. A modest weight loss of 5–10% of body weight typically decreases both SBP and DBP by approximately 5 mm Hg , while a 15% weight loss will frequently decrease SBP by 10 mm Hg .
Though it is axiomatic that the reduction in blood pressure typically accompanying intentional weight loss could result in decreased requirements for antihypertensive medications, the quantitative association between the magnitude of weight loss and the expected dose reductions or discontinuations of antihypertensive medications is not well studied. Establishing this quantitative association would be clinically useful in treating, counseling, and motivating hypertensive, obese patients considering or attempting weight loss.
Thus, in this study of overweight and obese patients who achieved weight loss of variable degrees, we attempted to establish the association between the magnitude of weight loss and the expected dose reductions or discontinuations of antihypertensive medications.
Materials and Methods
This retrospective cohort study was conducted in two university-based specialty outpatient weight management clinics, the Johns Hopkins Weight Management Center in Baltimore, Md., and the George Washington Weight Management program in Washington, D.C. Institutional review board approval was obtained for conducting the study. Informed consent was not obtained from the participants as the data were analyzed anonymously per institutional review board guidelines.
Case records of patients with a BMI >25 at the time of enrollment into the two weight management programs during the period from March 2008 to October 2011 were assessed for eligibility. Both were convenience samples. Patients were sampled if they had a diagnosis of essential hypertension at the time of enrollment into the programs, reported taking antihypertensive medications at the time of enrollment, and had at least 1 documented dose reduction or discontinuation of at least 1 of the antihypertensive medications before the study concluded in October 2011. Patients thus sampled formed the study cohort. The following exclusion criteria were applied: no diagnosis of hypertension at the time of enrollment into the programs or no documented dose reductions of antihypertensive medications (control group). Patients receiving treatment with 4 antihypertensive medications were excluded both from the study cohort and the control group as they present a more severe form of hypertension and are less likely to respond to weight loss. All excluded patients formed the excluded cohort.
Demographic data (age, gender, and race/ethnicity), cardiovascular risk factors (smoking, diabetes, and hypertension), medication history (antidiabetic medications, antihypertensive medications, and lipid-lowering drugs), clinical parameters (height, weight, SBP, and DBP), and laboratory parameters (fasting glucose, HbA1C, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides) were collected for the total cohort. BMI was calculated as per standard guidelines . Metabolic syndrome was determined using the National Cholesterol Education program (NCEP ATP III) guidelines . Hypertension was identified by physician diagnosis. All patients in our study had essential hypertension. There were none with secondary forms of hypertension. The severity of hypertension was classified using the Joint National Committee (JNC)-7 criteria .
The weight loss intervention protocols followed at the two participating clinics were similar and consisted of team-based, comprehensive evaluation and treatment for weight loss. The study participants had physician visits and evaluations on average twice a month. The baseline visit consisted of a physician-conducted medical history and physical examination, blood tests (as described above), and detailed dietary, behavioral, and exercise evaluations. Treatment was individualized but typically consisted of an approximately 1,000-kcal/day energy deficit diet, a behavior modification plan, and a plan for increasing physical activity utilizing both aerobic exercise and strength training. The diet composition was individualized but was generally low fat and initially mildly carbohydrate restricted as well. Meal replacements were often utilized as part of the diet prescription to improve adherence and increase weight loss. Depending on treatment response, the intervention was further tailored to address individual patient needs. The decision to alter the dose of or discontinue antihypertensive medications was based on the clinical judgment of the treating physicians. Factors considered in deciding dose reductions included symptoms and signs suggestive of orthostatic hypotension, magnitude of weight loss, blood pressure control, and the patient’s compliance to the weight management protocol.
The outcomes that were determined included the number (%) of patients achieving 5, 10, and 15% weight loss, time taken to reach those goals, mean SBP/DBP, mean SBP/DBP reduction, number of discontinuations, and number of dose reductions of antihypertensive medications associated with 5, 10, and 15% weight loss, and weight and blood pressure at study exit.
Patients exited the cohort if they required an increase in dose or restarting of an antihypertensive medication after the initial dose reduction or discontinuation (defined as relapse) or were administratively censored at study conclusion. The decision to restart or increase the dose of antihypertensive medications was individualized by the treating physicians, taking into account blood pressure as monitored over 2–3 consecutive visits. The time between the visit when the last documented medication dose reduction occurred until the visit when the patients relapsed was defined as time to relapse.
Data were expressed as number (%) for categorical variables and as mean ± standard deviation for continuous variables. Two-group comparisons were performed using Student’s t test and χ2 test, as appropriate.
Baseline characteristics, weight changes, blood pressure changes, and the outcome variables described above were compared between the study cohort and excluded cohort participants who failed to achieve dose reductions despite success with weight loss (control group). Then, multiple linear regression and multiple logistic regression analyses were performed to identify the association between percent weight loss (centered at 5%) and the mean percent dose reductions of antihypertensive medications (for multiple linear regression) and discontinuation of any antihypertensive medications (coded as dichotomous variable for logistic regression) for the study cohort [adjusted for age, gender, JNC class, baseline BMI, number of antihypertensive medications, and type 2 diabetes mellitus (DM) diagnosis]. Multiple logistic regression analyses were also performed to identify factors associated with relapse using the study cohort (adjusted for age, gender, JNC class, baseline BMI, number of antihypertensive medications, and type 2 DM diagnosis). For all these analyses, individuals treated with 4 antihypertensive medications (2 patients) were excluded as they present a more severe form of hypertension and hence were less likely to respond to weight loss. Akaike’s information criteria and Hosmer-Lemeshow goodness-of-fit were used as needed while determining the variables to be included in the model . A p value <0.05 was considered statistically significant. All analyses were performed using Stata 11.0 statistical software (StataCorp, College Station, Tex., USA).
In total, 179 patient records (107 from Johns Hopkins and 72 from George Washington) were identified and reviewed. Of these, 77 (43%) were excluded (excluded cohort) because of the following exclusion criteria: no diagnosis of hypertension (30, 17%) or no documented dose reductions of antihypertensive medications despite success at weight loss (control group; n = 47, 26%). The remaining 102 (57%) patients formed the study cohort. Further, 2 patients from the study cohort and 10 patients from the control group were excluded as they were receiving treatment with 4 antihypertensive medications. Hence, the final analytical sample size for the study cohort was 100 (56%) patients, and the control group consisted of 37 (21%) patients. The mean duration of hypertension among the study cohort was 9 ± 3.5 years. Demographic characteristics, medication details, and patient follow-up information are shown in table 1 and in online supplementary tables S1 and S2 (for all online suppl. material, see www.karger.com?doi=10.1159/000347048).
|Table 1. Baseline characteristics of the study cohort and the control group|
The study cohort showed a significant weight loss (12.2 ± 3.4 kg) and significant SBP/DBP reductions (9.1/6.3 mm Hg), with 91 (89%), 46 (46%), and 18 (18%) of the patients achieving 5, 10, and 15% weight loss, respectively, by the time of study exit (table 2). In comparison, the 37 participants from the excluded cohort who did not achieve dose reductions despite some weight loss (control group) presented nonsignificant weight losses (3.9 ± 3.1 kg) and nonsignificant SBP/DBP reductions (2.5/2 mm Hg), with only 6 (22%) achieving 5% weight loss and none achieving 10 or 15% weight loss.
|Table 2. Weight loss and antihypertensive drug dose reduction/discontinuation (study cohort n = 100)|
In the study cohort, for 5, 10, and 15% weight loss, 3, 39, and 39% in the respective groups achieved at least 1 discontinuation of any antihypertensive medication (table 2). Also, for 5, 10, and 15% weight loss, 8, 42, and 21 dose reductions were observed in the respective groups (table 2). Dose reductions or discontinuations occurred in all classes of antihypertensive medications with similar magnitudes of weight loss (online suppl. table S3). Figures 1 and 2 detail blood pressure and medication changes of the study cohort with weight loss.
|Fig. 1. SBP and DBP drop with % weight loss (study cohort). The x-axis represents % weight loss the study cohort participants achieved during the follow-up period, and the y-axis represents changes in SBP and DBP.|
|Fig. 2. Probability of dose reduction of antihypertensive medication with weight loss. The x-axis represents % weight loss, and the y-axis represents the probability for dose reductions of antihypertensive medications. Diamonds represent each dose reduction that was observed, and the vertical bars represent the distribution density of dose reductions with weight loss.|
Additionally, 38 (38%) of the patients in the study cohort relapsed, with a weight regain of 8.3 ± 3.9 kg and an increase in SBP/DBP of 6.5 ± 2.5/3.5 ± 2 mm Hg. Though the blood pressure increases of relapsing patients were significantly higher, the weight regains were not significantly different from their weight at their last dose reduction.
For every 5% weight loss, the patients in the study cohort achieved 36% reductions in their antihypertensive medication dose and had a 29% higher probability of stopping one of their antihypertensive medications (table 3). Factors such as age, gender, JNC class, baseline BMI, number of antihypertensive medications, and DM diagnosis were not associated with relapse (online suppl. table S4).
|Table 3. Association between percentage weight loss (every 5%) and dose reductions/discontinuation of antihypertensive medications|
In this sample of overweight and obese adults, we observed that, with intentional weight loss of 5, 10, and 15% of starting body weight, 3, 38, and 39% of the patients, respectively, could achieve at least 1 discontinuation of an antihypertensive medication, and 8, 42 and 78 dose reductions of at least 1 antihypertensive medication were achieved.
The independent association between intentional weight loss and blood pressure reduction is well established [8,9,10]. The mechanism for this effect likely stems from the fact that obesity is typically a high-catecholamine and high-renin state [15,16,17]. Weight loss, by decreasing catecholamine, renin, and aldosterone levels, lowers blood pressure by decreasing vascular tone, reducing myocardial contractility, ameliorating the high-output state, reducing the intravascular fluid volume, and promoting natriuresis [15,16,17]. Of note, weight loss can thus potentially substitute for the mechanisms of action of all existing classes of antihypertensive medications. True to this hypothesis, with weight loss of similar magnitudes, we observed that it was possible to reduce the doses of antihypertensive medications of any class.
Most of the hormonal changes involved in obesity-associated hypertension correlate with the level of adiposity, and the degree of mitigation of these hormonal changes correlates with the magnitude of weight loss [18,19]. This may be why participants in the excluded cohort with nonsignificant weight loss had poorer blood pressure reduction and thus could not achieve reductions in dosage of their antihypertensive medications (control group).
It is noteworthy that over a third (37%) of the patients in the study cohort relapsed from their reductions in and/or discontinuations of antihypertensive medications. Hypertension, being a chronic, progressive disease, usually relapses when medication discontinuation is attempted [18,19]. Our analysis of patient factors associated with relapse revealed no significant associations. However, among patients who relapsed, though on average they had experienced some weight regain, the weight at the time of relapse was not significantly different from the weight at their last dose reduction. Thus, it is possible that the natural history of hypertension progression was being observed, resulting in relapse, or that even the modest, not statistically significant level of weight regain experienced may have partly reinstated the hormonal milieu, discussed earlier, that fosters hypertension among obese individuals.
We observed significantly greater magnitudes of weight loss (12.2 kg by 15 months of follow-up) and blood pressure reductions (SBP/DBP: 9.1/6.3 mm Hg at 15 months) compared to typical randomized controlled weight loss trials (weight loss: 4–6 kg within 12–15 months of follow-up, SBP/DBP: 3–4/2–3 mm Hg) [20,21]. It is thus possible that confounding due to unknown factors may have played a role. Or else, surveillance bias is possible due to the intensity of weight loss intervention being individualized and the decision to reduce the dose being subjective and at the discretion of the treating physicians. Additionally, the small sample size limited us from analyzing associations specific to individual medications and BMI categories. Finally, the study’s retrospective cohort design limited our data to whatever was recorded in the patient records.
We found that intentional weight loss was frequently an effective intervention for achieving discontinuations and dose reductions of all classes of antihypertensive medications. Validation of the results of our study with data from larger randomized controlled trials is needed. Since a report of the association between the magnitude of weight loss and dose reductions of antihypertensive medications is novel, these findings can help to inform the conduct of a systematic review using data from prior randomized controlled trials that have evaluated interventions for weight loss. Such information, if confirmed, can add a quantitative aspect to the oft-cited advice health-care providers give to obese, hypertensive patients: ‘lose weight, and you will reduce your blood pressure and need for medications’.
We thank Mr. Rohit Joshua Samson and Mr. Nelson David Boddu for their help with the chart review. Dr. Ghanshyam Palamaner Subash Shantha, MD, MPH, is supported in part by a NIH/NHLBI T32HL007024 Cardiovascular Epidemiology Training Grant for his research training at the Johns Hopkins Bloomberg School of Public Health.
Lawrence Jay Cheskin serves as a consultant and stockholder for Medifast, Inc. and Vivus, Inc. All other authors have no conflicts of interest to declare.
Lawrence J. Cheskin, MD, FACP
Director, Johns Hopkins Weight Management Center
550 North Broadway, Suite 1001
Baltimore, MD 21205 (USA)
Received: October 13, 2012
Accepted: January 7, 2013
Published online: February 15, 2013
Number of Print Pages : 9
Number of Figures : 2, Number of Tables : 3, Number of References : 21
Additional supplementary material is available online - Number of Parts : 1
Vol. 3, No. 1, Year 2013 (Cover Date: April 2013)
Journal Editor: Sowers J.R. (Columbia, Mo.)
ISSN: 1664-3828 (Print), eISSN: 1664-5502 (Online)
For additional information: http://www.karger.com/CRM