The Framingham Risk Score and Heart Disease in NAFLD
The Framingham Risk Score and Heart Disease in NAFLD
The accuracy of the Framingham risk score (FRS) in identifying patients with nonalcoholic fatty liver disease (NAFLD) at higher 10-year coronary heart disease (CHD) risk remains unknown. We aimed at evaluating both the baseline probability of CHD as predicted by the FRS and the actual long-term occurrence of CHD in NAFLD patients. This was a longitudinal study of a community-based cohort. A total of 309 NAFLD patients were followed up for 11.5 ± 4.1 years (total 3554 person-years). The overall calculated 10-year CHD risk was significantly higher in the NAFLD cohort than the absolute CHD risk predicted by the FRS for persons of the same age and gender (10.9 ± 9.3% vs. 9.9 ± 5.9%, respectively, P < 0.0001), and higher in men than women (12.6 ± 10.3% vs. 9.6 ± 8.1%, respectively, P = 0.006). New onset CHD occurred in 34 patients (11% vs. 10.9% predicted at baseline, P = NS), whereas 279 (89%) patients did not develop CHD. Using multivariable analysis, the FRS was the only variable significantly associated with new onset CHD (OR = 1.13, 95% CI = 1.05–1.21; P = 0.001). A FRS cut-point of 11 in women, and 6 in men had a sensitivity of 80% and 74%, respectively, and a negative predictive value of 97% and 93% respectively. NAFLD patients have a higher 10-year CHD risk than the general population of the same age and gender. The FRS accurately predicts the higher 10-year CHD risk in NAFLD patients, and helps identify those patients expected to derive the most benefit from early intervention to prevent CHD events.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in Western countries. An increasing prevalence of NAFLD is associated with the increasing prevalence of obesity and diabetes. Obesity and diabetes are significantly associated with increasing cardiovascular events and mortality. The mortality rate of NAFLD patients has been found to be higher than that in the general USA population, and, cardiovascular events was the first or second most common cause of death in four large series of patients with NAFLD confirmed by liver biopsy or imaging. Thus, current evidence indicates that NAFLD, obesity and the metabolic syndrome have a strong association, and that one of the most common causes of death among NAFLD patients is cardiovascular disease. However, the absolute proportion of patients with NAFLD dying from cardiovascular events is relatively small, and increases from 3.8% within 8 years of NAFLD diagnosis [2] to about 12% within 20 years of NAFLD diagnosis. In addition, some recent studies that have used elevated alanine aminotransferase (ALT) as a surrogate for NAFLD diagnosis have failed to show a significant association between ALT levels and cardiovascular mortality. Furthermore, ALT seems to exhibit a U-shaped association with total mortality, and the association of ALT with cardiovascular events may be similarly shaped with increased risk also apparent at low ALT concentrations.
Two recent reviews of the literature had reached conflicting conclusions. Ghouri et al. concluded that the association between NAFLD and cardiovascular risk is inconsistent and that a diagnosis of NAFLD is insufficient to consider NAFLD patients as being at high risk for cardiovascular disease. Targher et al., however, recommended monitoring and evaluation of the risk of cardiovascular disease in all patients with NAFLD. Thus, although cardiovascular events are a common cause of death in NAFLD, there is conflicting evidence to recommend routine counselling and cardiovascular risk screening in all patients with NAFLD. Based on all this, it seems more important to identify the subgroup of NAFLD patients at higher risk for cardiovascular disease who are expected to derive the most benefit from early intervention to prevent cardiovascular outcomes.
The Framingham risk score (FRS) provides an estimate for the coronary heart disease (CHD) risk of the general United States population. Small cross-sectional studies have reported a predicted higher 10-year CHD risk as determined by the FRS in patients with NAFLD. However, as patients included in those studies were evaluated at a single point in time and they had no long-term follow-up, it remains unclear whether the proportion of NAFLD patients predicted with a high risk for CHD in fact was the same proportion of patients who developed CHD over time. Thus, we aimed at evaluating both the baseline probability of CHD using the FRS, and the long-term occurrence of CHD in NAFLD patients who underwent long-term follow-up. We also assessed the sensitivity, specificity, and positive and negative predictive values of the FRS in predicting CHD in NAFLD patients.
Abstract and Introduction
Abstract
The accuracy of the Framingham risk score (FRS) in identifying patients with nonalcoholic fatty liver disease (NAFLD) at higher 10-year coronary heart disease (CHD) risk remains unknown. We aimed at evaluating both the baseline probability of CHD as predicted by the FRS and the actual long-term occurrence of CHD in NAFLD patients. This was a longitudinal study of a community-based cohort. A total of 309 NAFLD patients were followed up for 11.5 ± 4.1 years (total 3554 person-years). The overall calculated 10-year CHD risk was significantly higher in the NAFLD cohort than the absolute CHD risk predicted by the FRS for persons of the same age and gender (10.9 ± 9.3% vs. 9.9 ± 5.9%, respectively, P < 0.0001), and higher in men than women (12.6 ± 10.3% vs. 9.6 ± 8.1%, respectively, P = 0.006). New onset CHD occurred in 34 patients (11% vs. 10.9% predicted at baseline, P = NS), whereas 279 (89%) patients did not develop CHD. Using multivariable analysis, the FRS was the only variable significantly associated with new onset CHD (OR = 1.13, 95% CI = 1.05–1.21; P = 0.001). A FRS cut-point of 11 in women, and 6 in men had a sensitivity of 80% and 74%, respectively, and a negative predictive value of 97% and 93% respectively. NAFLD patients have a higher 10-year CHD risk than the general population of the same age and gender. The FRS accurately predicts the higher 10-year CHD risk in NAFLD patients, and helps identify those patients expected to derive the most benefit from early intervention to prevent CHD events.
Introduction
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in Western countries. An increasing prevalence of NAFLD is associated with the increasing prevalence of obesity and diabetes. Obesity and diabetes are significantly associated with increasing cardiovascular events and mortality. The mortality rate of NAFLD patients has been found to be higher than that in the general USA population, and, cardiovascular events was the first or second most common cause of death in four large series of patients with NAFLD confirmed by liver biopsy or imaging. Thus, current evidence indicates that NAFLD, obesity and the metabolic syndrome have a strong association, and that one of the most common causes of death among NAFLD patients is cardiovascular disease. However, the absolute proportion of patients with NAFLD dying from cardiovascular events is relatively small, and increases from 3.8% within 8 years of NAFLD diagnosis [2] to about 12% within 20 years of NAFLD diagnosis. In addition, some recent studies that have used elevated alanine aminotransferase (ALT) as a surrogate for NAFLD diagnosis have failed to show a significant association between ALT levels and cardiovascular mortality. Furthermore, ALT seems to exhibit a U-shaped association with total mortality, and the association of ALT with cardiovascular events may be similarly shaped with increased risk also apparent at low ALT concentrations.
Two recent reviews of the literature had reached conflicting conclusions. Ghouri et al. concluded that the association between NAFLD and cardiovascular risk is inconsistent and that a diagnosis of NAFLD is insufficient to consider NAFLD patients as being at high risk for cardiovascular disease. Targher et al., however, recommended monitoring and evaluation of the risk of cardiovascular disease in all patients with NAFLD. Thus, although cardiovascular events are a common cause of death in NAFLD, there is conflicting evidence to recommend routine counselling and cardiovascular risk screening in all patients with NAFLD. Based on all this, it seems more important to identify the subgroup of NAFLD patients at higher risk for cardiovascular disease who are expected to derive the most benefit from early intervention to prevent cardiovascular outcomes.
The Framingham risk score (FRS) provides an estimate for the coronary heart disease (CHD) risk of the general United States population. Small cross-sectional studies have reported a predicted higher 10-year CHD risk as determined by the FRS in patients with NAFLD. However, as patients included in those studies were evaluated at a single point in time and they had no long-term follow-up, it remains unclear whether the proportion of NAFLD patients predicted with a high risk for CHD in fact was the same proportion of patients who developed CHD over time. Thus, we aimed at evaluating both the baseline probability of CHD using the FRS, and the long-term occurrence of CHD in NAFLD patients who underwent long-term follow-up. We also assessed the sensitivity, specificity, and positive and negative predictive values of the FRS in predicting CHD in NAFLD patients.