There is a well-established link between dyslipidemia and cardiovascular events, although this risk is modified by age. Little is known about how treatment of dyslipidemia and low-density lipoprotein (LDL) cholesterol goal attainment differ between older and younger patients. We obtained clinical data from 9,926 dyslipidemic patients across 9 countries in North and Latin America, Europe, and Asia from 2006 through 2007. Multivariate regressions were performed to determine predictors of lipid level goal attainment. The study sample consisted of 5,733 adults <65 and 4,193 adults ≥65 years old. Compared with younger patients, older patients were more likely to have diabetes (32.5% vs 30.0%, p = 0.0014) and hypertension (73.4% vs 57.0%, p <0.0001), to be classified as high risk (68.6% vs 53.2%, p <0.0001), and to be taking a statin (79.1% vs 72.0%, p <0.0001). However, they were less likely to smoke (8.2% vs 17.6%, p <0.0001) or to have metabolic syndrome (29.0% vs 34.4%, p <0.0001). Older patients had lower LDL cholesterol levels (95.1 vs 103.9 mg/dl, p <0.0001) and higher levels of high-density lipoprotein cholesterol (54.2 vs 51.5 mg/dl, p <0.0001). LDL cholesterol goal attainment was 74.7% in older and 71.1% in younger patients (p = 0.036). Older patients were more likely to achieve LDL targets whether low risk (89.8% vs 84.6%, p = 0.002), moderate risk (79.0% vs 71.9%, p = 0.0006), or high risk (70.5% vs 64.4%, p <0.0001). In conclusion, older patients had different risk profiles and better lipid levels compared with their younger counterparts. They were more likely to attain their LDL cholesterol goal, perhaps because of greater statin use, different risk profiles, or survival bias.
The Lipid Treatment Assessment Project (L-TAP) 2 surveyed almost 10,000 dyslipidemic adults across 9 countries from 2006 through 2007 and reported that low-density lipoprotein (LDL) cholesterol goal attainment overall was 73% compared with 37% in the original L-TAP study a decade previously. Scant data exist comparing LDL cholesterol goal attainment in older versus younger patients. The purpose of this L-TAP 2 substudy was to compare clinical features, risk, and lipid goal attainment between the 4,193 patients ≥65 years of age and the 5,733 patients <65 years of age.
Methods
The design of L-TAP 2 has been described in detail elsewhere. Patients were eligible if they were ≥20 years old and had been treated with the same lipid-lowering therapy for ≥3 months. Diet and exercise were permissible lipid-lowering therapies. Patients were excluded if any of the following conditions were present: major trauma, surgery requiring anesthesia, or hospitalization <12 weeks; acute infection requiring antibiotic therapy; change in usual diet <1 month; pregnancy, breastfeeding, or postpartum <6 months; myocardial infarction <12 weeks; any unstable medical condition; life expectancy <6 months; or treatment with an investigational lipid-altering drug or device within 30 days of the study visit. All patients gave written informed consent, and the study was approved by an institutional review board where required.
The enrollment goal was 3,000 patients in the United States; 1,000 patients each in Canada, Spain, the Netherlands, France, Taiwan, and Korea; 400 patients in Brazil; and 600 patients in Mexico. Cluster sampling was used, with a cluster defined as each physician-investigator. Each investigator was expected to enroll approximately 20 patients. In total 10,174 patients were enrolled from September 2006 through April 2007; 248 (2.4%) were excluded because of missing values, thus leaving 9,926 patients for the final analysis.
A history of smoking, alcohol use, previous coronary disease or other atherosclerotic events, hypertension, diabetes, early family history of coronary or atherosclerotic disease, hypothyroidism, nephrotic syndrome, liver disease, and any other significant medical condition were obtained from each patient at the study visit. Current cholesterol medications, if any, including dose and duration of therapy and any nonpharmacologic interventions for dyslipidemia (diet, exercise) were recorded. Height, weight, waist circumference, and blood pressure were measured. A venous blood sample was drawn after fasting for ≥8 hours. All samples were analyzed in a central laboratory (MDS Pharma Services Central Laboratory, Mississauga, Ontario, Canada) for total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, blood glucose, and high-sensitivity C-reactive protein with a Roche Modular Analyzer (Roche, Basel, Switzerland). LDL cholesterol was calculated by the Friedewald formula. Metabolic syndrome was diagnosed by the National Cholesterol Education Program Adult Treatment Panel III definition.
Patients were classified into low-, moderate-, and high-risk groups, with low-risk patients being those with ≤1 risk factor, moderate-risk patients being those with ≥2 risk factors, and high-risk patients classified as those with coronary or other atherosclerotic vascular disease or diabetes. In this subanalysis, LDL cholesterol goals were set according to coronary heart disease (CHD) risk group as defined by National Cholesterol Education Program Adult Treatment Panel III guidelines (low-risk patients, LDL cholesterol goal <160 mg/dl; moderate-risk patients, LDL cholesterol goal <130 mg/dl; high-risk patients and those with CHD, LDL cholesterol goal <100 mg/dl). The optional goal of LDL cholesterol <70 mg/dl was assessed in patients with CHD and in patients with CHD and ≥2 additional risk factors. Low HDL cholesterol levels were defined as <40 mg/dl in men and <50 mg/dl in women.
Demographic, clinical, and laboratory characteristics were compared between patients ≥65 and those <65 years old using logistic regression for categorical variables and analysis of variance for continuous variables. LDL cholesterol success and low HDL cholesterol rates were compared between patients ≥65 and those <65 years old using logistic regression. Results were compared among CHD risk groups and geographic regions (Asia, Europe, Latin America, and North America). Multivariate analyses were performed to determine independent predictors of LDL cholesterol success and low HDL cholesterol levels using stepwise regression. A 2-sided p value <0.05 was considered statistically significant. All analyses were performed using SAS 9.2 (SAS Institute, Cary, North Carolina).
Results
Table 1 lists characteristics of the study sample, consisting of 5,733 adults <65 years old and 4,193 adults ≥65 years old. Patients ≥65 years old were more likely to be women, to have hypertension and diabetes, and to be classified as high risk for CHD. On average, older patients had lower levels of LDL cholesterol and triglycerides and higher HDL cholesterol levels compared with patients <65 years old. More patients in the older compared with the younger group were taking a statin (79.1% vs 72.0%, p <0.0001).
| Variable | Age (years) | p Value | |
|---|---|---|---|
| ≥65 (n = 4,193) | <65 (n = 5,733) | ||
| Men | 2,176 (51.8%) | 3,237 (56.4%) | <0.0001 |
| Age (years) | 72.5 ± 5.6 | 53.8 ± 8.3 | <0.0001 |
| Weight (kg) | 75.2 ± 16.3 | 81.9 ± 19.4 | <0.0001 |
| Body mass index (kg/m 2 ) | 27.8 ± 4.9 | 29.2 ± 8.0 | <0.0001 |
| Waist circumference (cm) | 96.2 ± 16.5 | 97.2 ± 16.9 | 0.055 |
| Hypertension | 3,078 (73.4%) | 3,271 (57.0%) | <0.0001 |
| Family history of coronary heart disease | 1,005 (23.9%) | 1,892 (33.0%) | <0.0001 |
| Diabetes mellitus | 1,364 (32.5%) | 1,724 (30.0%) | 0.0014 |
| Metabolic syndrome | 1,217 (29.0%) | 1,973 (34.4%) | <0.0001 |
| Smoker | 347 (8.2%) | 1,011 (17.6%) | <0.0001 |
| Statin therapy | 3,319 (79.1%) | 4,131 (72.0%) | <0.0001 |
| Coronary heart disease risk | |||
| Low | 619 (14.7%) | 1,418 (24.7%) | <0.0001 |
| Moderate | 696 (16.5%) | 1,263 (22.0%) | |
| High | 2,878 (68.6%) | 3,052 (53.2%) | |
| Region | |||
| Asia | 815 (19.4%) | 1,134 (19.7%) | <0.0001 |
| Europe | 1,266 (30.1%) | 1,654 (28.8%) | |
| Latin America | 376 (8.9%) | 612 (10.6%) | |
| North America | 1,736 (41.4%) | 2,333 (40.6%) | |
| Lipids | |||
| Total cholesterol (mg/dl) | 177.2 ± 40.7 | 186.9 ± 44.0 | <0.0001 |
| Low-density lipoprotein cholesterol (mg/dl) | 95.1 ± 33.8 | 103.9 ± 38.0 | <0.0001 |
| High-density lipoprotein cholesterol (mg/dl) | 54.2 ± 15.2 | 51.5 ± 14.3 | <0.0001 |
| Triglycerides (mg/dl) | 141.1 ± 72.1 | 159.2 ± 93.9 | <0.0001 |
| Triglycerides/high-density lipoprotein cholesterol | 3.0 ± 2.3 | 3.5 ± 3.0 | <0.0001 |
| C-reactive protein (mg/L) | 1.5 (2.5%) | 1.5 (2.6%) | 0.15 |
Overall, 74.7% of older and 71.1% of younger patients attained their LDL cholesterol goal (p = 0.036). This finding was consistent across the 3 risk groups: in the low-risk group success rates were 89.8% in older and 84.6% in younger patients (p = 0.002); in the moderate-risk group rates were 79.0% and 71.9% (p = 0.0006); and in the high-risk group rates were 70.5% and 64.4% (p <0.0001). An interaction was present by geographic region (p = 0.01); older patients were more likely to attain their LDL cholesterol goal in Europe (70.0% vs 65.2%, p = 0.006) and North America (79.7% vs 74.0%, p <0.0001) but not in Asia or Latin America.
Predictors of LDL cholesterol goal attainment according to age category are listed in Table 2 . In the 2 age groups statin therapy was the strongest predictor of LDL cholesterol goal attainment (odds ratios >2). Presence of diabetes predicted failure to attain LDL cholesterol treatment goals in the 2 age groups.
| Predictor | ≥65 Years Old | <65 Years Old | ||
|---|---|---|---|---|
| OR (95% CI) | p Value | OR (95% CI) | p Value | |
| Statin therapy | 2.92 (2.30–3.71) | <0.0001 | 2.06 (1.59–2.67) | <0.0001 |
| Diabetes mellitus | 0.83 (0.71–0.96) | 0.015 | 0.52 (0.46–0.60) | <0.0001 |
| Triglycerides/high-density lipoprotein cholesterol (per 1-SD change) ⁎ | 0.85 (0.77–0.93) | 0.0003 | — | NS |
| Smoking (never vs current) | — | NS | 1.31 (1.12–1.54) | 0.004 |
| Hypertension | — | NS | 0.75 (0.65–0.87) | 0.0002 |
| Family history of coronary heart disease | — | NS | 0.80 (0.71–0.91) | 0.0008 |
| Region | NS | 0.002 | ||
| Asia vs Europe | — | 1.20 (0.90–1.60) | ||
| Asia vs Latin America | — | 0.78 (0.53–1.17) | ||
| Asia vs North America | — | 0.88 (0.66–1.16) | ||
| Europe vs Latin America | — | 0.65 (0.47–0.91) | ||
| Europe vs North America | — | 0.73 (0.61–0.87) | ||
| Latin vs North America | — | 1.12 (0.80–1.56) | ||
Overall HDL cholesterol levels were below the recommended cutpoints in 26.4% of those ≥65 years old and 31.3% of those <65 years old (p <0.0001). This difference extended across the 3 risk groups, with HDL cholesterol levels being lower in older patients in the low-risk group (6.1% vs 17.2%, p <0.0001), moderate-risk group (30.1% vs 35.3%, p = 0.019), and high-risk group (29.9% vs 36.1%, p <0.0001) and in patients with CHD (30.0% vs 34.7%, p = 0.006).
Factors that were predictive of low HDL cholesterol levels are listed in Table 3 and were similar in the 2 age groups: female gender, higher body mass index (BMI), and larger waist circumference. Statin therapy, higher LDL cholesterol levels, and never smoking were negative predictors of low HDL cholesterol levels in the 2 groups. Asia was associated with more failure to reach HDL cholesterol cutpoints and Europe with less compared with the other geographic regions, particularly in patients ≥65 years old.
| Predictor | ≥65 Years Old | <65 Years Old | ||
|---|---|---|---|---|
| OR (95% CI) | p Value | OR (95% CI) | p Value | |
| Female gender | 1.41 (1.20–1.66) | <0.001 | 1.61 (1.42–1.83) | <0.001 |
| Age ⁎ | — | NS | 0.87 (0.82, 0.92) | <0.001 |
| Diabetes mellitus | 1.48 (1.27–1.72) | <0.001 | 1.45 (1.27–1.64) | <0.001 |
| Body mass index (per 1-SD increase) ⁎ | 1.29 (1.18–1.41) | <0.001 | 1.24 (1.11–1.38) | 0.001 |
| Waist circumference ⁎ | 1.15 (1.05–1.25) | 0.002 | 1.20 (1.10–1.30) | <0.001 |
| Statin therapy | 0.69 (0.53–0.90) | 0.016 | 0.60 (0.49–0.73) | <0.001 |
| Low-density lipoprotein cholesterol ⁎ | 0.77 (0.71–0.84) | <0.001 | 0.75 (0.70–0.80) | <0.001 |
| Smoking (never vs current) | 0.61 (0.47–0.79) | <0.001 | 0.73 (0.62–0.86) | <0.001 |
| Region | <0.001 | <0.001 | ||
| Asia vs Europe | 2.47 (1.97–3.09) | 1.77 (1.47–2.13) | ||
| Asia vs Latin America | 1.82 (1.35–2.44) | 1.11 (0.89–1.39) | ||
| Asia vs North America | 1.36 (1.12–1.67) | 1.06 (0.90–1.26) | ||
| Europe vs Latin America | 0.74 (0.55–0.98) | 0.63 (0.51–0.78) | ||
| Europe vs North America | 0.55 (0.46–0.67) | 0.60 (0.51–0.70) | ||
| Latin vs North America | 0.75 (0.57–0.99) | 0.95 (0.78–1.16) | ||
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