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Journal of Occupational & Environmental Medicine:
doi: 10.1097/JOM.0b013e3181a2fec7
Original Articles

Economic Impact of the BP DownShift Program on Blood Pressure Control Among Commercial Driver License Employees

Greene, Beth L. BA; Miller, Jeffrey D. MS; Brown, T Michelle PhD; Harshman, Robert S. MD; Richerson, Gerald T. AET, BSE; Doyle, Joseph J. RPh, MBA

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Author Information

From Abt Bio Pharma Solutions, Inc. (Ms Greene, Mr Miller, Dr Brown), Lexington, Mass; Georgia Power/Southern Company (Dr Harshman, Mr Richerson), Atlanta, Ga; and Novartis Pharmaceuticals Corporation (Mr Doyle), East Hanover, NJ.

Address correspondence to: T. Michelle Brown, PhD, Abt Bio-Pharma Solutions, Inc., 181 Spring Street, Lexington, MA 02421; E-mail:

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Objective: To assess the economic impact of a hypertension educational and awareness program (“BP Downshift”) on improvement in blood pressure among commercial driver license (CDL) employees in a large southeastern U.S. electric utility company.

Methods: An economic simulation model was developed to evaluate the costs/cost savings the company realized from implementation of the BP DownShift Program in terms of changes in work productivity, CDL certification status, hypertension treatment, cardiovascular disease events, and diabetes care.

Results: Model results showed a 16.3% (more than $540,000) reduction in costs for a sample of 499 CDL employees over 2 years. On a per-employee basis, 2-year cost savings were estimated to be $1084, or $542 annually.

Conclusions: Study results will interest employers who are considering using disease management and health promotion programs to control costs of hypertension and other chronic illnesses.

Hypertension is a highly prevalent, modifiable disease affecting approximately one in three U.S. adults (about 73 million persons).1,2 The relationship between high blood pressure and risk of cardiovascular disease (CVD), cerebrovascular disease, and peripheral vascular disease is well established, and it follows that hypertension is a major public health threat in the U.S.2–8 Given the large epidemiologic burden of hypertension, it is not surprising that the economic consequences of high blood pressure and its resultant comorbid conditions also are high.9–15 The total direct and indirect cost of hypertension treatment in the U.S. was estimated to be $69.4 billion in 2008.2 This estimate increases to more than $100 billion when the cost of subsequent complications of CVD is included.10,11,16 Even so, the true total costs of hypertension may be undervalued because high blood pressure is usually not listed as a secondary or contributing cause in the majority of deaths attributed to CVD.11

Because of the significant prevalence of hypertension in the working-age population, employers bear a major cost burden for hypertension.17–21 Companies employing commercial drivers face particular hurdles related to hypertension, not only from the detriments to their employees’ health, but also from the danger and liability associated with traffic accidents from impaired or incapacitated employees while driving. To help mitigate this risk, the Department of Transportation (DOT) restricts commercial driver’s licenses (CDLs) to drivers who meet certain standards for healthy blood pressure.22 The DOT hypertension qualifications define drivers with systolic blood pressure (SBP) higher than 140 mm Hg and diastolic blood pressure (DBP) over 90 mm Hg as hypertensive, and further classifies them by severity (stages 1, 2, and 3 hypertension) (Table 1). CDL employees must undergo frequent monitoring of blood pressure, with time limits for controlling high blood pressures before disqualification. The DOT guidelines provide a strong incentive for companies to help their CDL employees maintain a healthy blood pressure and control hypertension. However, employers must bear the costs associated with blood pressure monitoring and other medical tests required for CDL certification. Moreover, self-insured employers typically pay for the treatment necessary to achieve control.

Table 1
Table 1
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An increasing number of employers are using disease management and health promotion programs to control the economic burden of hypertension and other chronic illnesses.20,21,23 Many studies suggest that such programs improve clinical outcomes and quality of patient care.24–27 In one systematic review, four of eight analyses of disease management programs targeting hypertension found that the programs produced significant reductions in mean SBP, by 2 to 12 mm Hg more than controls not enrolled in the programs.26 Although this degree of reduction may seem small, it has the potential to move a large number of employees with stage 1 hypertension back into the “normal”/“controlled” range in which blood pressure will not interfere with CDL certification. Other benefits potentially could come from: 1) reduced medical expenditures (for both employees and their families), 2) reduced sick and disability leave, and 3) improved on-the-job productivity.

In 2004, a large southeastern U.S. electric utility company implemented a disease management and health promotion program to help CDL employees maintain or restore a healthy blood pressure and to meet DOT hypertension guidelines for CDL employees. After 2 years of operation, the BP Downshift Program successfully helped the utility company improve the health of its employees, thereby reducing risk of medical disqualification, lowering the frequency of recertification, and diminishing the potential for road accidents.24 It was unknown, however, how these positive results generated by the BP Downshift Program translated into economic benefits for the utility company. The objective of this study, therefore, was to assess the economic impact of the BP DownShift Program in terms of costs and cost savings realized by the utility company from improvement in blood pressure readings among its CDL employees.

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We developed an economic simulation model to evaluate the 2-year impact of the BP DownShift Program on direct and indirect costs associated with changes in hypertension for a random sample of 499 CDL employees employed by a large southeastern U.S. utility company. With institutional review board approval, the BP Downshift Program was designed specifically for commercial drivers to provide all current CDL employees with educational materials explaining the importance of blood pressure control, both in lowering their cardiovascular risk and in maintaining their CDL certification. Employees also received resources to help them understand and manage hypertension; these included antihypertensive treatment information, suggested questions for their physician, blood pressure diaries with tips and a tool to track blood pressure readings, and medical chart stickers, an audio CD that explains high blood pressure and uses real-life experiences to show how it can be managed, and medical chart stickers to share with health care professionals to identify them as a CDL holder and needing to meet specific blood pressure goals. Employees received verbal counseling during their periodic medical examination for CDL certification, or during multiple employee health fairs during 2004. If needed, employees were referred by the corporate medical director back to their personal physician or cardiologist for follow up. In addition to the materials provided to the employees, the BP DownShift Program also supplied tools to the employer, employee unions, and the physicians caring for CDL employees, to help promote hypertension awareness and participation in the program.

The software platform for the model consisted of a series of linked Microsoft Excel spreadsheets, each tabbed according to function and included a simple, easy-to-understand user interface, resident data tables, and other underlying statistical information. Tabular and graphical outputs were generated automatically from scenario analyses specified by the model user. We followed model-building guidelines published by the International Society for Pharmacoeconomics and Outcomes Research throughout the design and development process.28,29

The model operated on the basis of two scenarios: 1) simulation of the 2-year clinical-economic outcomes in the CDL population if BP Downshift had not been implemented (ie, “pre-BP DownShift”); 2) simulation of the same economic outcomes in the same population after implementing BP Downshift (ie, “post-BP Downshift”). The incremental difference between the total costs in these two scenarios constituted the financial impact of the BP DownShift Program. The conceptual flow of the model’s logic is illustrated in Fig. 1.

Fig. 1
Fig. 1
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We presupposed costs or cost savings from implementation of the BP Downshift Program would come from three areas: 1) employee lost or gained time and productivity; 2); CDL certification or recertification examinations and licensure; and 3) treatment of chronic diseases (coronary heart disease [CHD], stroke, hypertension, and diabetes). The primary source of data was a CDL employee database maintained by the utility company, which included numerous health outcomes—most importantly registration of changes in blood pressure levels before and 2 years after the implementation of BP Downshift. Details about the data collection efforts and the timeline over which they were conducted have been reported elsewhere.24 Using these data, effects on CDL licensure before and after implementation of BP Downshift could be established, and estimates of lost or gained work time and productivity (and any associated costs or cost savings) could be ascertained. Moreover, by applying the CDL employee’s clinical data (supplementing them with National Health and Nutrition Examination Survey [NHANES]30 data were data gaps existed) in Framingham Heart Study CVD risk equations enabled us to model the occurrence of CHD and stroke events and their associated costs in the CDL employee population. Details of our methodology and the data sources underlying it are described in detail below.

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Clinical or Demographic Parameters and Data Sources

Clinical or demographic model parameters primarily came from the Medical Examination Reports, which are completed as part of each employee’s periodic medical examination for CDL certification.31 Data abstracted from Medical Examination Reports included demographics (age, gender, CDL class, and status), employee-reported medical history (cardiovascular conditions or risk factors and other comorbidities, and medication use), and the results of physical evaluations (including assessments of blood pressure and of height and weight used to calculate body mass index [BMI]). Generally, CDL employees with a history of normal blood pressure and no major health problems are examined for recertification every 2 years; those with hypertension or other serious health problems must be examined more frequently (Table 1).22 The length of time between examinations for CDL employees typically varies depending on the severity of hypertension and presence of other health conditions. For purposes of our model, an employee’s “baseline” examination was the most recent examination conducted before the implementation of the BP DownShift Program. The “follow-up” examination was defined as the most recent examination administered after program implementation (Fig. 2). Additional clinical parameters were generated using results generated using the aforementioned data entered into Framingham Heart Study risk equations to predict occurrence of CVD events. All the clinical model parameters and their data sources are summarized in Table 2.

Fig. 2
Fig. 2
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Table 2
Table 2
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Table 2
Table 2
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A comprehensive analysis of the DOT Medical Examination Reports of a random sample of 501 employees at the utility company (representing approximately 25% of the company’s entire CDL employee population of 2038) who participated in the BP DownShift Program has been reported elsewhere.24 Because crucial model parameter data were missing for two of the 501 employees, a subset (ie, 499 CDL employees) of that analysis data set is used in our model (hence, some of the statistics reported here may differ slightly from what were previously reported).24 Also, the diabetes status of each CDL employee was held at its pre-BP Downshift level to keep results of the model partial only to the influences of hypertension. Each of the 499 CDL employees with their unique health status and CDL certification profiles was “run” through the model on an individual basis and then aggregate statistical results were generated from the entire sample.

Two Framingham Heart Study risk equations (one for predicting CHD events and the other for predicting stroke events) were used to estimate occurrence of CVD events among the 499 CDL employee over the model’s 2-year simulation time horizon—first under the hypothetical scenario that the BP DownShift Program had not been implemented using baseline data from the DOT Medical Reports (ie, “pre-BP Downshift”) and then under the real-world scenario of actual implementation of the BP DownShift Program using follow-up data from the DOT Medical Examination Reports (ie, “post-BP Downshift”). We then applied unit costs and labor productivity impact values to the number of CVD events predicted by the risk equations to derive the total economic impact associated with CVD.

The CHD risk prediction equation was one of the Framingham Heart Study health risk appraisal models published by D’Agostino et al32 that estimate the relation between risk factors and the occurrence of primary CHD events, separately for men and women, and separately for persons who are free of CVD and for persons with a history of CHD or ischemic stroke. The equation is based on a Weibull accelerated failure time model facilitating risk estimation over the course of 1 to 4 years, with a time frame set to 2 years in our model. Because all 499 CDL employees in our model were men, and because the version of the risk equation pertaining to subsequent CHD events does not include blood pressure as a contributory variable, we used the primary CHD event equation for men to estimate occurrence of both initial and subsequent CHD events. Consistent with the definition provided by the Framingham Heart Study, CHD was defined to include myocardial infarction, coronary insufficiency, and angina pectoris.32 Key variables in the CHD equation are age, total cholesterol or high-density lipoprotein-cholesterol ratio, SBP, use of anti-hypertension medication, diabetes, and smoking status. Data sources for these variables are shown in Table 2. To isolate the true effects of BP DownShift on the CHD event occurrence, all variables were held constant for the pre- and post-BP Downshift scenarios, except for SBP and use of anti-hypertension medication.

The Framingham Heart Study risk equation for stroke event was from a health risk appraisal function published by D’Agostino et al,33 improving on Wolf et al.34 The equation is based on a Cox proportional hazards regression model that permits the computation of stroke probabilities for variable lengths of follow-up, ranging from 1 to 10 years, with a time frame set to 2 years in our model. The equation was used in the model to calculate the likelihood of each of the 499 CDL employees having a stroke, based on the following variables: age, SBP, use of anti-hypertension medication, CVD history, left ventricular hypertrophy, smoking status, atrial fibrillation, and diabetes. Consistent with the definition used by FHS, stroke included atherothrombotic brain infarction, transient ischemic attack only, cerebral embolus, intracerebral hemorrhage, and subarachnoid hemorrhage.

Although the DOT Medical Examination Reports were the primary data source for the variables in the CHD and stroke risk equations, data gaps required supplemental data from the National Health and Nutrition Examination Survey (NHANES) 2001–2004 data set,30 with its nationally representative sample of the U.S. population, and further supplementation by estimates from published literature. Affected variables in the risk equations included: total cholesterol, high-density lipoprotein cholesterol, smoking status, left ventricular hypertrophy, and atrial fibrillation (Table 2).

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Economic Model Parameters and Data Sources

Cost parameters (2007 USD and discounted at an annual rate of 3%) were obtained from employer records and published literature, and included costs for treatment of chronic disease (CHD, stroke, hypertension, and diabetes), CDL certification examinations, and employer lost time and productivity.

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Costs for Treatment of Chronic Diseases

As described by Russell et al35 (and adjusted to 2007 USD), costs related to CHD in the first year in which an event occurred were $14,541, which include hospitalization and professional services costs, pharmacy fees, and home health care expenditure. Derived from this same source, CHD follow-up costs (ie, costs related to CHD after the first year in which an event occurred) were $1702, which include hospitalization costs, professional services costs, and pharmacy fees (long-term custodial and nursing care were not included). Costs related to a stroke in the first year in which an event occurred, including inpatient hospital, professional services, and inpatient rehabilitation were $19,767, as estimated by Thompson et al36 and adjusted to 2007 USD. From this same data source, costs related to a stroke after the first year in which an event occurred were $4961, including nursing home care, physician visits, physical therapists, speech therapists, home health care, inpatient acute, and rehabilitation care for recurrent strokes. The annual cost of treating patients for hypertension was estimated as $1053 by averaging the costs (adjusted to 2007 USD) of office visits, laboratory tests, and medications, as reported by Odell and Gregory37 using a similar approach used by other researchers.38,36 Annual Diabetes care costs were $518, and were limited to the cost of oral agents (given that insulin-dependent diabetes is one of the exclusion criteria for CDL workers),22 as derived from Hogan et al39 and adjusted to 2007 USD.

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Work Productivity and CDL Examinations.

The economic impact of the BP Downshift Program on work productivity among the CDL employees was an explicit part of the model and the parameters are summarized in Table 2. The areas of focus were: 1) lost work time due to CDL examinations; 2) lost work time due to CDL disqualification; and 3) worker absenteeism and presenteeism directly due to hypertension, CHD, stroke, and diabetes. The number of hours required for CDL examinations was estimated by the utility company and weighted by location of the examination (85% were conducted off-site for 3 hours; 15% were conducted on-site for 1 hour). Work-loss hours were multiplied by the average wage rate for the CDL employees to yield the cost of lost productivity. The average hourly rate for CDL employees (data supplied by the utility company) was $34.00. Also, according to information supplied by the utility company, CDL examination costs (direct only, excluding lost work time) were $150 for on-site examinations and $175 off-site examinations. This was multiplied by the number of examination visits required in the 2-year time period according to Table 1. Work hours lost due to CDL disqualification was assumed to be 0, because the utility company CDL employees work in crews and can still perform their regular work even if unable to drive. The impact of BP Downshift Program on worker absenteeism and presenteeism due to illness was another factor modeled. Using data extracted from the 2006 National Health Interview Survey (NHIS),40 absenteeism was incorporated in the model due to hypertension (44 hours lost per year), CHD (63 hours lost per year), stroke (79 hours lost per year), and diabetes (63 hours lost per year). Using data published by Goetzel et al,17 presenteeism was incorporated in the model due to hypertension (156 hours lost per year), CHD (130 hours lost per year), stroke (130 hours lost per year; assumed to be the same as for CHD), and diabetes (234 hours lost per year).

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Results generated by the model show that although average SBP of the cohort of CDL employees increased by about one point (Table 2), the overall allocation of the employees in the DOT hypertension classification changed in favorable ways (Table 3). After implementation of the BP Downshift Program, the number of CDL employees in DOT hypertension classification “Normal” increased by nearly 11% (n = 40). Correspondingly, there was a 31.0% decrease in the number of employees classified with uncontrolled blood pressure (pre-BP Downshift, n = 129; post-BP DownShift, n = 89), reflecting a 31% decrease in “DOT stage 1,” a 22% decrease in “DOT stage 2,” and a complete elimination of employees in “DOT stage 3.”

Table 3
Table 3
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The model projected small increases overall in the number of CHD events (0.7%) and stroke events (0.3%) in the CDL population, which was attributable to the small (0.8% on average) increase in SBP among the employees over the 2-year observation period. Substantial reduction (>27%) in risk of CHD and stroke events was projected for employees in the stages 1, 2, and 3 hypertension categories.

These clinical benefits of the BP Downshift Program translated into meaningful economic benefits. A 16.3% reduction in total employer costs for the 499 CDL employees was observed over 2 years (pre-BP DownShift: $3312,220; post-BP DownShift: $2771,094) (Table 4 and Fig. 3). Therefore, cost savings to the electric utility from implementation of the BP DownShift Program for these 499 employees was $541,126 over the 2 years, or about $271,000 annually.

Table 4
Table 4
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Fig. 3
Fig. 3
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As a general observation, regardless of the BP Downshift Program, costs were highest for CDL employees with stages 1, 2, and 3 hypertension, ranging from $17,000 to $19,000 per employee over 2 years (Fig. 4). As expected, costs were lowest for CDL employees with normal blood pressure ($2000 to $3000), but ranging from about $1000 for employees with untreated normal blood pressure to more than $7000 for employees taking medication to bring their blood pressure into normal limits. Implementation of the BP Downshift Program had a discernable effect on overall per-employee costs. On this basis, 2-year costs declined from $6638 to $5553 (pre- and post-BP Downshift, respectively) per CDL employee, producing a 2-year cost savings of $1084 per CDL employee, or $542 per CDL employee annually. Extrapolated to the utility company’s entire CDL employee population (n = 2038 in 2005), total cost savings realized by the company would be about $1,100,000 annually.

Fig. 4
Fig. 4
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Most of the cost savings realized by the BP Downshift Program were attributable to improvements in lost time and productivity ($552,103), which comprised 83% and 79% of all costs pre- and post-BP Downshift, respectively (Fig. 3). There also were cost savings from fewer CDL certification re-examinations ($8410), although the contribution of these examinations to total costs grew from 5% to 6% pre- and post-BP Downshift, respectively. There were cost increases for treatment of hypertension, CHD, and stroke ($19,387 in total), but nearly 97% of this increase was strictly attributable to hypertension treatment, probably as a result of implementation of the BP Downshift Program. Indeed, the number of employees taking antihypertensive medication increased by nearly 19% (from 25.5% to 30.3% of employees) after implementation of the BP Downshift Program (Tables 2 and 3).

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Although hypertension is a major risk factor for adverse health outcomes and can be fairly easy to monitor and treat, control levels are poor in the working-age population, particularly among CDL employees. In the CDL employee population of this study, 40% of the employees have treated or untreated hypertension, whereas the national average is about 26% for adult men.41 Unlike more acute conditions that frequently result in hospitalization and loss of function, the immediate cost offsets of controlling hypertension are less defined. In the past, health care payers mainly focused on the immediate short-term costs of treating hypertension, paying less attention to potential long-term cost savings of fewer CVD events and other comorbid sequelae.42

Fortunately, greater attention is now being paid to worksite hypertension detection and intervention programs that identify undiagnosed or untreated hypertension among workers, which lay the groundwork for early, cost-saving interventions. Evidently, these programs are making a difference.43 The program of focus in our study, the BP Downshift Program—an innovative hypertension management and health promotion program designed for CDL drivers—significantly improved blood pressure control among the CDL employees of a self-insured utility company. Better blood pressure control was shown to move employees into lower-risk categories, improve outcomes, and help to extend certification periods and prevent disqualification.24 In addition to the expected benefits to health and driving safety of lowering high blood pressure, improved recertification rates are likely promoting a more stable and productive workforce for the employer, and may be helping to reduce the long-term costs of treating hypertension and its sequelae. Indeed, results of our modeling analyses demonstrate that changes emanating from the BP Downshift Program translated into meaningful cost savings for the utility company—as much as $542 per CDL employee each year, with overall annual savings to the utility company as much as $1,100,000.

Disease management programs that incorporate pharmacoeconomic analysis and computerized methods of targeting patients at high risk of hypertensive sequelae are known to be useful and cost-effective tools.44 To our knowledge, we have developed the first economic model of hypertension disease management program targeting CDL employees. Our findings emphasize the high costs to employers associated with hypertension—particularly for lost productivity—and the benefits that interventions such as an employer-sponsored disease management programs can have. Consequently, results of this study will be of interest to other large, self-insured employers with CDL employees, as well as disease management decision-makers in the public and private health care sectors.

Some limitations of our study bear mention. First, the ability to generalize our results to other employers may be problematic. A bias is introduced by the extensive restrictions on individuals who qualify for a CDL, excluding, for example, employees who have insulin-dependent diabetes or longstanding uncontrolled hypertension. Consequently, results from the CDL population may not be comparable to employee populations without equivalent medical restrictions on their employment. Previous studies accounting for the impact of hypertension on employment have shown that hypertension costs range from $392 to $1174 annually per employee with the condition.17,18 Results from our study indicate that the annual costs for CDL employees with controlled hypertension (ie, receiving treatment medication) are about $3800, but may be as high as $9700 for employees with uncontrolled hypertension (annualizing values in Fig. 4). We believe that differences between our results and results from previous studies are due to differences in cost accounting. However, another discrete driver of the cost differences may be that our study targets a specific population (ie, CDL employees working for an electric utility) known to have elevated risk for comorbidity associated with hypertension (ie, obesity, sedentary lifestyle, poor nutrition, age etc.).

Another limitation of our study is the relatively short, 2-year analysis time frame. Although there are benefits of lowering blood pressure that are immediately discernable, the beneficial impact on likelihood of CVD events and other organ-damaging sequelae is most noticeable over long periods of observation. Nonetheless, our model predicts 5.16 CHD events and 1.64 stroke events over 2 years among the 499 CDL employees (under the post-BP Downshift scenario) (Table 3). The total number of CVD events (6.80) is quite close to what occurred in reality, where six CDL employees had a CVD event in the 2-year period (based on self-reported health measures). Of course, the definition of “CVD” is broader than just CHD and stroke events, but the approximation of the results is interesting nonetheless. Once longer-term data become available (eg, 5 years), it is the intention of the authors to re-analyze the data and re-run the model analyses to determine whether the impact of the BP Downshift Program was sustained, and to see whether the cardiovascular benefits became more pronounced. Also there may be opportunity to include some factors that were not accounted for by the current model, such as replacement costs for employees who become permanently disqualified from CDL, costs of long-term disability for employees who are unable to continue working due to health problems, and accident-related liability costs.

Other limitations of this study are worth noting as well. Some of the data used in the model were self-reported, which tend to be less reliable than objectively documented data. The CDL population in this study may have been motivated to under-report previously-diagnosed hypertension and other health conditions due to the threat to their CDL certification and, ultimately, their terms of employment. In addition, we acknowledge that employees may have made lifestyle modifications in the 4 to 15 months between their baseline examination and their enrollment in the BP Downshift Program, in which case not all health benefits may be solely attributable to the BP Downshift Program. This exception may be particularly relevant to those employees who were considered at a high risk of losing their CDL certification, and thus were motivated to make lifestyle modifications to become healthier. Finally, we note that because DOT hypertension guidelines are more liberal than the JNC 7 guidelines, caution should be taken when making comparisons to other populations that do not have DOT restrictions.

As a final note, our use of Framingham Heart Study equations for predicting risk of CHD and stroke events pre- and post-BP DownShift have some limitations. The equations we chose to employ in the model only include SBP as a variable. Consequently, to the extent that the BP Downshift Program affected DBP independent of SBP may have resulted in an underestimation of the clinical and economic benefits of the BP Downshift Program. Furthermore, a common criticism of Framingham Heart Study risk equations arises from the sociodemographic homogeneity of the population from which they were derived. Although caution must be exercised in extrapolating from the Framingham Heart Study cohort of predominantly middle class, white persons, the risk equations have been shown to be reasonably accurate when applied to other populations.45–47

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We found that a hypertension management and health promotion program targeting an electric utility company’s CDL drivers resulted in significantly improved control of hypertension and that the improved health benefits led to a significant reduction in employer-borne costs over a 2-year period. Results of this study will be of interest to the growing number of employers who are using (or are considering using) disease management and health promotion programs to control the cost burdens of hypertension and other chronic illnesses. For the electric utility company in this study, results of the analyses will be used to better understand the health and productivity costs of a major segment of its workforce. Given continuing and increasing costs for the treatment and control of hypertension and its associated conditions, further investigation is warranted to assess the long-term economic impact of the BP DownShift Program on the utility company.

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This research was funded by Novartis Pharmaceuticals Corporation.

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