- Email: [email protected]
TELOMERE LENGTH AND CARDIOVASCULAR OUTCOMES
E356 JACC March 27, 2012 Volume 59, Issue 13
Acute Coronary Syndromes TELOMERE LENGTH AND CARDIOVASCULAR OUTCOMES ACC Oral Contributions McCormick Place South, S401a Sunday, March 25, 2012, 9:15 a.m.-9:30 a.m.
Session Title: What Impacts Outcomes in ACS? From Genes to Plaque Morphology to Environment. Abstract Category: 5. Acute Coronary Syndromes: Clinical Presentation Number: 916-8 Authors: Christian T. Ruff, Jessica Mega, David Morrow, Benjamin Scirica, Edward C. Frackelton, Hakon Hakonarson, Kevin Crowley, Charles Contant, Christopher Cannon, Eugene Braunwald, Marc Sabatine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Background: Telomeres are DNA-protein complexes at the ends of chromosomes and are essential for preserving genome integrity. Preliminary data suggest a correlation between telomere attrition, atherosclerosis and adverse cardiovascular (CV) outcomes in stable CAD. Methods: We measured telomere length (quantitative PCR) in 5,057 patients (pts) w/ ACS from MERLIN-TIMI 36 and PROVE-IT TIMI 22 followed for a mean of 1.2 yrs. We evaluated the risk of CV death, MI, or stroke stratified by tertiles of telomere length and adjusted for differences in baseline characteristics. Results: Shorter telomeres were associated w/ older age, lower BMI, NSTEACS vs STEMI, prior MI and prior stroke. Telomere length demonstrated a strong graded relationship with the risk of CV death, MI or stroke, with pts w/ shorter telomeres having the highest event rates (Figure Left; P<0.0001). This relationship was consistent across age groups (Figure Right). After adjustment, short telomeres remained strongly associated w/ the risk of the composite endpoint (T1 HR 2.39, 95% CI 1.95-2.93, P<0.0001; T2 HR 1.47, 1.19-1.82, P=0.0004) as well as the individual components of CV death (T1 vs T3 HR 3.27, 1.91-5.59), MI (HR 1.81, 1.36-2.42) and stroke (HR 3.00, 2.22-4.07) (P<0.0001 for each). Conclusions: Telomere attrition demonstrates a strong, independent association with adverse CV outcomes in patients with ACS. Telomere length may provide the basis for a biological clock which integrates the cumulative effects of biological stressors.
Acute Coronary Syndromes TELOMERE LENGTH AND CARDIOVASCULAR OUTCOMES ACC Oral Contributions McCormick Place South, S401a Sunday, March 25, 2012, 9:15 a.m.-9:30 a.m.
Session Title: What Impacts Outcomes in ACS? From Genes to Plaque Morphology to Environment. Abstract Category: 5. Acute Coronary Syndromes: Clinical Presentation Number: 916-8 Authors: Christian T. Ruff, Jessica Mega, David Morrow, Benjamin Scirica, Edward C. Frackelton, Hakon Hakonarson, Kevin Crowley, Charles Contant, Christopher Cannon, Eugene Braunwald, Marc Sabatine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Background: Telomeres are DNA-protein complexes at the ends of chromosomes and are essential for preserving genome integrity. Preliminary data suggest a correlation between telomere attrition, atherosclerosis and adverse cardiovascular (CV) outcomes in stable CAD. Methods: We measured telomere length (quantitative PCR) in 5,057 patients (pts) w/ ACS from MERLIN-TIMI 36 and PROVE-IT TIMI 22 followed for a mean of 1.2 yrs. We evaluated the risk of CV death, MI, or stroke stratified by tertiles of telomere length and adjusted for differences in baseline characteristics. Results: Shorter telomeres were associated w/ older age, lower BMI, NSTEACS vs STEMI, prior MI and prior stroke. Telomere length demonstrated a strong graded relationship with the risk of CV death, MI or stroke, with pts w/ shorter telomeres having the highest event rates (Figure Left; P<0.0001). This relationship was consistent across age groups (Figure Right). After adjustment, short telomeres remained strongly associated w/ the risk of the composite endpoint (T1 HR 2.39, 95% CI 1.95-2.93, P<0.0001; T2 HR 1.47, 1.19-1.82, P=0.0004) as well as the individual components of CV death (T1 vs T3 HR 3.27, 1.91-5.59), MI (HR 1.81, 1.36-2.42) and stroke (HR 3.00, 2.22-4.07) (P<0.0001 for each). Conclusions: Telomere attrition demonstrates a strong, independent association with adverse CV outcomes in patients with ACS. Telomere length may provide the basis for a biological clock which integrates the cumulative effects of biological stressors.