Obesity is associated with hypertension, dyslipidemia, and diabetes, but it is also an independent cardiovascular risk factor. We sought to evaluate the differences in treatment patterns and attainment of guideline-recommended targets among high-risk vascular outpatients in relation to their body mass index (BMI). The prospective Vascular Protection and Guideline Orientated Approach to Lipid Lowering Registries recruited 7,357 high-risk vascular outpatients in Canada from 2001 to 2004. We stratified the patient population into 3 groups according to their BMI: normal weight (BMI <24.9 kg/m 2 ), overweight (BMI 25 to 29.9 kg/m 2 ), and obese (BMI >30 kg/m 2 ). We evaluated the rates of attainment for contemporary guideline targets of blood pressure (<140/90 or <130/80 mm Hg in the presence of diabetes) and lipids (low-density lipoprotein [LDL] <2.5 mmol/L [96.7 mg/dl] and total cholesterol [TC]/high-density lipoprotein [HDL] ratio <4.0). Of the 7,357 patients, 1,305 (17.7%) were normal weight, 2,791 (37.9%) overweight, and 3,261 (44.4%) obese, as determined by the BMI. Obese patients were younger and more likely to have hypertension and diabetes (all p <0.001 for trend). Obese patients had higher baseline blood pressure, TC, LDL cholesterol, triglyceride levels and TC/HDL ratio, and lower HDL cholesterol. Obese patients were more likely to be treated with antihypertensive agents (p = 0.002), angiotensin-converting enzyme inhibitors (p = 0.024), angiotensin receptor blockers (p <0.001), and high-dose statin therapy (p = 0.001). On multivariable analyses, obese patients were less likely to attain the blood pressure (odds ratio 0.77, 95% confidence interval 0.66 to 0.90, p = 0.001) and TC/HDL ratio (odds ratio 0.48, 95% confidence interval 0.42 to 0.55, p <0.001) targets but not the LDL targets (odds ratio 0.89, 95% confidence interval 0.78 to 1.03, p = 0.11). In conclusion, only a minority ambulatory patients at high cardiovascular risk achieved both guideline-recommended blood pressure and lipid targets, and this significant treatment gap was more pronounced among obese patients. Our findings underscore the opportunity to optimize the treatment of these high-risk patients.
Obesity is a risk factor for hypertension, dyslipidemia, and diabetes and is associated with cardiovascular disease. Current obesity treatment guidelines have stressed lifestyle modification and control of other associated risk factors to decrease obesity-related morbidity and mortality. Practice guidelines have established optimal targets for blood pressure and lipid parameters. Several studies have examined the attainment of these lipid and blood pressure targets in patients at high cardiovascular risk and those with confirmed cardiovascular disease. In addition, a recent population-based study examined the relation between obesity and control of cardiac risk factors in subjects without known cardiovascular disease. However, it is not known whether differences exist in the attainment of guideline-recommended targets in obese versus nonobese high vascular risk patients. Also, limited data are available on whether any differences exist in the treatment patterns for obese patients. Studies have suggested that obese patients might be more aggressively treated with medications and interventions than nonobese patients. We herein aimed to examine (1) the attainment of blood pressure and lipid targets in ambulatory patients stratified by body mass index (BMI); (2) treatment patterns in relation to BMI in two Canadian high vascular risk patient registries.
Methods
The present study was a cross-sectional analysis of the prospective observational Guidelines Orientated Approach to Lipid Lowering (GOALL) and Vascular Protection (VP) registries. The objectives of these registries were to examine clinical management practices and identify gaps between the patient care recommended in guidelines and that delivered in the “real world.” Overall, 278 physicians participated in the VP registry and 254 in the GOALL registry; most (>95%) were general practitioners. Participation in the registries was completely voluntary, and all enrolled patients provided written informed consent. Enrollment occurred from December 2001 to December 2004. Two independent ethics boards approved the study protocols.
Both the GOALL and VP registries sought to recruit patients at high risk of, or with confirmed, cardiovascular disease. The inclusion criteria for cardiovascular disease included coronary artery disease, cerebrovascular disease, and peripheral vascular disease, according to standard definitions. In addition, the VP registry enrolled diabetic patients with at least one other cardiac risk factor (systolic blood pressure >140 mm Hg, diastolic blood pressure >90 mm Hg, or the use of antihypertensive medication; total cholesterol [TC] >5.2 mmol/L [201 mg/dl], or high-density lipoprotein [HDL] cholesterol <0.9 mmol/L [34.8 mg/dl]; current cigarette smoking; microalbuminuria). The GOALL registry also included any diabetic patients and elderly patients (age >65 years) with ≥2 risk factors (as for the VP registry). The registries had no exclusion criteria, and the physicians were encouraged to enroll consecutive patients. The present study included only those patients with established cardiovascular disease or diabetes.
The participating physicians collected all data using standardized case report forms. The data collected included patient demographics, cardiovascular risk factors, history of atherosclerotic disease, medication use, height, weight, heart rate, blood pressure, routine blood work values, and medication use.
Plasma lipid measurements were performed in commercial laboratories, as part of routine clinical practice. Fasting plasma glucose and a complete lipid profile, including TC, low-density lipoprotein (LDL) cholesterol, HDL-C, and triglycerides (TG), were collected within 6 months of study entry. Patients with familial hypercholesterolemia (TC >9.4 mmol/L [363.5 mg/dl], LDL cholesterol >6.8 mmol/L [263 mg/dl], and/or TG >4.5 mmol/L [394 mg/dl]) were excluded from the present analysis, because it would have precluded calculation of LDL cholesterol using the Friedewald formula. Blood pressure, waist circumference, and height and weight measurements were recorded by the physician. The BMI was calculated by dividing the weight in kilograms by the square of the height in meters. Complete data on the lipid profile and height and weight were available for 7,357 patients.
The completed case report forms were returned to the Canadian Heart Research Centre and scanned into an electronic database. Queries regarding incomplete or unclear data on case report forms were sent to the study investigators for completion or correction.
Both the National Cholesterol Education Program Adult Treatment Panel III and Canadian guidelines in place at the time of the registries recommended very similar target for LDL cholesterol (<2.6 mmol/L [100 mg/dl] and <2.5 mmol/L [97 mg/dl], respectively) for high vascular risk patients. The Canadian guidelines included a TC/HDL cholesterol ratio of <4.0 as a secondary lipid target. The optimal blood pressure was <140/90 mm Hg for nondiabetic and <130/80 mm Hg for diabetic patients.
In the present analysis, the primary outcome measure was the attainment of the guideline-recommended lipid LDL cholesterol goal (<2.5 mmol/L [97 mg/dl]) and blood pressure targets (<140/90 mm Hg or <130/80 mm Hg for diabetic patients). Secondary outcome measures included a TC/HDL ratio <4.0, TG <2.0 mmol/L (177 mg/dl), and the use of antiplatelet, antihypertensive, and lipid-modifying agents.
The patient population was stratified into 3 groups according to their BMI: normal weight (BMI ≤24.9kg/m 2 ), overweight (BMI 25.0 to 29.9 kg/m 2 ), and obese (BMI ≥30 kg/m 2 ). To determine whether our results would be different using other anthropometric measures of obesity, we repeated our analysis using the waist circumference. The population was stratified into 3 groups : normal (waist circumference <93.9 cm for men and 79.9 cm for women), overweight (waist circumference 94 to 101.9 cm for men and 80 to 87.9 cm for women), and obese (waist circumference >102 cm for men and 88 cm for women). The statin dose was classified as low, standard, and high using previously published criteria.
Continuous variables are summarized as medians with the twenty-fifth and seventy-fifth percentiles (or means ± standard deviation for normally distributed data), and group comparisons were made using the t test or analysis of variance. Categorical variables are presented as percentages and were compared using the chi-square test. We used Kendall’s tau-b and chi-square test for trend for the continuous and categorical variables, respectively. We performed multivariable logistic regression analysis to determine the factors associated with attainment of the blood pressure and lipid targets. From the results of previous studies and bivariate analyses, the predictor variables considered in the models were age, gender, alcohol use, smoking, diabetes, previous coronary revascularization, history of coronary artery disease, history of heart failure, and use of antihypertensive, statin, and other lipid-modifying drugs. We report the adjusted odds ratios with 95% confidence intervals. We performed statistical analyses using the Statistical Package for Social Sciences, version 12.0 (SPSS, Chicago, Illinois). A 2-sided probability value of <0.05 was considered statistically significant.
Results
Of the 7,357 patients in the present study, 1,305 (17.7%) were normal weight, 2,791 (37.9%) overweight, and 3,261 (44.4%) obese based on BMI. The patient demographics and clinical characteristics are summarized in Table 1 . Compared to the normal weight and overweight groups, the obese patients were younger and more likely to have a history of hypertension and diabetes (p <0.001). In contrast, the obese patients were less likely to have a history of coronary artery disease, peripheral vascular disease, or cerebrovascular disease (p <0.001). Obese patients had higher resting heart rate, systolic and diastolic blood pressure.
| All Patients (n = 7,357) | BMI (kg/m 2 ) | p Value ⁎ | |||
|---|---|---|---|---|---|
| <24.9 (n = 1,305) | 25–29.9 (n = 2,791) | >30 (n = 3,261) | |||
| Age (years) | 65 ± 11 | 68 ± 11 | 66 ± 11 | 63 ± 11 | <0.001 |
| Women | 35.1% | 39.2% | 28.7% | 38.9% | 0.02 |
| Hypertension | 62.5% | 52.5% | 57.7% | 70.5% | <0.001 |
| Diabetes mellitus | 57.8% | 42.8% | 50.8% | 69.9% | <0.001 |
| Family history | 34.5% | 33.2% | 34.5% | 34.9% | 0.33 |
| Smoker | 15.1% | 18.7% | 14.1% | 14.5% | 0.003 |
| Coronary artery disease | 52.4% | 58.5% | 58.0% | 45.1% | <0.001 |
| Myocardial infarction | 29.4% | 32.7% | 33.1% | 24.9% | <0.001 |
| Coronary artery bypass | 16.3% | 18.2% | 18.7% | 13.4% | <0.001 |
| Percutaneous coronary intervention | 12.8% | 15.2% | 14.3% | 10.5% | <0.001 |
| Peripheral vascular disease | 10.8% | 15.4% | 11.4% | 8.4% | <0.001 |
| Cerebrovascular disease | 13.3% | 16% | 14.3% | 11.3% | <0.001 |
| Heart failure | 7.9% | 8.9% | 7.5% | 7% | 0.012 |
| Creatinine (μmol/L) | 92 ± 31 | 94 ± 35 | 93 ± 28 | 92 ± 32 | 0.001 |
| Alcohol use (drinks/wk) | 0.071 | ||||
| None | 49.7% | 55.6% | 47% | 49.6% | |
| Light, <5 | 37.5% | 33.5% | 38.8% | 38.1% | |
| Moderate, 6–10 | 9.7% | 7.8% | 11.2% | 9.2% | |
| Heavy, >10 | 3.1% | 3.1% | 3.2% | 3.1% | |
| Weight (kg) | 81.8 (70.9, 93.6) | 63.6 (57.3, 70) | 78 (70.9, 84.6) | 94 (85, 104) | <0.001 |
| Waist circumference (cm) | 101 (92, 110) | 87 (81, 92) | 97 (92, 103) | 110 (103, 118) | <0.001 |
| Height (cm) | 168 (160, 174) | 167 (159, 173) | 169 (161, 175) | 166 (158, 173) | <0.001 |
| Heart rate (beats/min) | 72 (66.78) | 71 (64.76) | 71 (64.76) | 73 (68.78) | <0.001 |
| Systolic blood pressure (mm Hg) | 132 (120, 140) | 130 (120, 140) | 131 (120, 140) | 134 (122, 140) | <0.001 |
| Diastolic blood pressure (mm Hg) | 76 (70, 80) | 74 (70, 80) | 76 (70, 80) | 78 (70, 82) | <0.001 |
The medication use and lipid profiles for the 3 groups are summarized in Table 2 . Obese patients had higher TC, LDL cholesterol, TG, TC/HDL cholesterol and lower HDL cholesterol. Obese patients were significantly less likely to have received treatment with any antiplatelet agent (p = 0.011). No significant difference was found among the 3 groups with respect to treatment with any lipid-modifying medication or statins. The obese patients were more likely to be treated with nonstatin lipid-modifying therapy (p <0.001). Of those patients treated with statins, the obese patients were significantly more likely to be treated with a high dose. Obese patients were also more likely to be treated with antihypertensive medications (p = 0.002), angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (p <0.001) but less likely to be treated with β blockers (p = 0.006).
| Lipid Profile | All Patients (n = 7,357) | BMI (kg/m 2 ) | p Value ⁎ | ||
|---|---|---|---|---|---|
| <24.9 (n = 1,305) | 25–29.9 (n = 2,791) | >30 (n = 3,261) | |||
| Total cholesterol | |||||
| mmol/L | 4.74 ± 1.08 | 4.72 ± 1.14 | 4.7 ± 1.07 | 4.78 ± 1.06 | 0.001 |
| mg/dl | 183 ± 41.8 | 183 ± 44.1 | 182 ± 41.4 | 185 ± 41 | |
| Low-density lipoprotein cholesterol | |||||
| mmol/L | 2.7 ± 0.92 | 2.68 ± 0.96 | 2.68 ± 0.91 | 2.72 ± 0.92 | 0.014 |
| mg/dl | 104 ± 35.6 | 104 ± 37.1 | 104 ± 35.2 | 105 ± 35.6 | |
| Triglycerides | |||||
| mmol/L | 1.83 ± 0.84 | 1.59 ± 0.80 | 1.77 ± 0.83 | 1.98 ± 0.84 | <0.001 |
| mg/dl | 162 ± 74.4 | 141 ± 70.9 | 157 ± 73.5 | 175 ± 74.4 | |
| High-density lipoprotein cholesterol | |||||
| mmol/L | 1.21 ± 0.33 | 1.32 ± 0.38 | 1.21 ± 0.34 | 1.16 ± 0.30 | <0.001 |
| mg/dl | 46.8 ± 12.8 | 51 ± 14.7 | 46.8 ± 13.2 | 44.9 ± 11.6 | |
| Total cholesterol/high-density lipoprotein cholesterol ratio | 4.14 ± 1.24 | 3.78 ± 1.15 | 4.08 ± 1.24 | 4.33 ± 1.23 | <0.001 |
| Glucose | |||||
| mmol/L | 7.1 ± 2.5 | 6.4 ± 2.2 | 6.8 ± 2.4 | 7.5 ± 2.6 | <0.001 |
| mg/dl | 128 ± 45 | 115 ± 40 | 122 ± 43 | 135 ± 47 | |
| Medication use | |||||
| Aspirin | 75.1% | 74.7% | 76.4% | 74.3% | 0.41 |
| Any antiplatelet agent | 78.9% | 79.8% | 80.4% | 77.2% | 0.011 |
| Statin | 78.4% | 77.6% | 79.9% | 77.3% | 0.36 |
| Statin dose | |||||
| Low | 10.2% | 11.8% | 10.8% | 9.1% | |
| Standard | 76.3% | 77.6% | 75.1% | 76.8% | |
| High | 13.5% | 10.7% | 14.1% | 14.1% | 0.001 |
| Any lipid-modifying agent | 80.1% | 79% | 81.1% | 79.6% | 0.94 |
| Nonstatin lipid-modifying agent | 3% | 2.1% | 2.5% | 3.8% | 0.001 |
| Any antihypertensive agent | 87.9% | 85% | 88.4% | 88.7% | 0.002 |
| Angiotensin-converting enzyme inhibitor | 56.1% | 52.4% | 57% | 56.8% | 0.024 |
| Angiotensin receptor blocker | 19.9% | 16.2% | 17.9% | 23.2% | <0.001 |
| β Blocker | 40.3% | 41.2% | 42.6% | 38.4% | 0.006 |
| Insulin | 7.3% | 4.1% | 6.1% | 9.6% | <0.001 |
Overall, only 46.6% of patients achieved the target LDL cholesterol goal of <2.5 mmol/L (97 mg/dl) and 42.4% attained the blood pressure target of <140/90 mm Hg (<130/80 mm Hg for diabetic patients). Figures 1 and 2 show the percentages of patients attaining the targets in the 3 groups. Obese patients were less likely to achieve the target LDL cholesterol (p = 0.021), TG (p <0.001), TC/HDL cholesterol ratio <4.0 (p <0.001), and blood pressure (p <0.001) targets. Only 21.4% of patients achieved the composite end point of LDL cholesterol <2.5 mmol/L (97 mg/dl) and blood pressure <140/90 mm Hg (<130/80 mm Hg for diabetic patients). Obese patients were also less likely to meet this combined endpoint compared to the normal weight and overweight groups (p <0.001).
In multivariable logistic regression analysis, obese patients were less likely to meet the target blood pressure, after adjusting for other independent predictors ( Table 3 ). Obesity was also an independent predictor for failure to meet the target TC/HDL cholesterol ratio <4.0 ( Table 4 ) but not LDL cholesterol <2.5 mmol/L (97 mg/dl) ( Table 5 ).
