We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major card... more We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major cardiovascular (CV) events and investigated the mitigating effects of low-density lipoprotein cholesterol (LDL-C) lowering and LDL-C-lowering plus high-density lipoprotein cholesterol (HDL-C) raising. This analysis combined individual patient data from 445 subjects who participated in 3 double-blinded, randomized, placebo-controlled trials (FATS, HATS, and AFREGS) comparing intensive lipid therapy to placebos on coronary stenosis progression by quantitative coronary angiography and on major CV events. The primary endpoints were the change in mean proximal coronary diameter stenosis (Δ%Sprox) over 3 years and the frequency of the pre-defined composite of coronary artery disease (CAD) death, nonfatal myocardial infarction (MI), stroke and revascularization due to worsening ischemia. Patients with the MS had 50% more rapid coronary stenosis progression and 64% increased CV event frequency compared to those without. More rapid coronary stenosis progression was significantly and independently associated with 3.5-fold increased event risk (p<0.001). Combination lipid therapy significantly decreased stenosis progression by 83% (Δ%Sprox=0.5 vs. 2.9, p<0.001) in patients with MS, and induced a small net regression in those without (Δ%Sprox=−0.3 vs. 2.0, p<0.001). Combination therapy reduced the event rate by 54% (13 vs. 28%, p=0.03) in those with MS and by 82% (3 vs. 17%, p=0.002) without. On average, each 10% reduction in LDL-C or 10% increase in HDL-C was significantly associated with 0.3 Δ%Sprox reduction. Each 10% LDL-C-lowering or 10% HDL-C-raising was associated with 11% (p=0.02) or 22% (p<0.001) event risk reduction. In conclusion, patients with MS have significantly more rapid coronary stenosis progression and a higher frequency of CV events. Greater stenosis progression rate is associated with a higher event rate. LDL-C-lowering and HDL-C-raising therapies independently and significantly decrease coronary stenosis progression and reduce CV events.
Evidence supports the idea that substantial benefits may derive from treatments that increase hig... more Evidence supports the idea that substantial benefits may derive from treatments that increase high density lipoprotein (HDL) cholesterol (HDL-C), apolipoprotein (apo) A-I, HDL2 (or 2b) or the size of HDL particles with, or without, apo A-II. HDL3 appears to be neutral in terms of coronary artery disease risk, and apo A-II appears to be adverse. Because HDL particles serve as antioxidants in vitro, the hypothesis that low HDL-C reflects an antioxidant deficiency state appears tenable. Based on these observations, a three-year angiographic study was proposed and received funding. Enrollment began in January 1995 and was completed in January 1997.
Patients with established coronary disease and abnormalities of lipid metabolism represent a part... more Patients with established coronary disease and abnormalities of lipid metabolism represent a particularly important subgroup, since their mortality risk is typically 10 times greater than that amongst-subjects with comparable risk factors but no clinical history. Such patients are commonly treated initially with anti-anginal therapy; if ischaemic symptoms persist they often undergo revascularization (bypass or angioplasty). While invasive procedures restore blood flow and relieve ischemia, they do not, in most cases, reduce risk of subsequent MI or death, or alter the underlying atherogenic process(es). Despite this, there has been a progressive 54% decline in age-adjusted cardiac mortality over the period 1960-1995, which appears best attributable to US lifestyle changes. In particular, the past decade has provided compelling evidence for the merits of a fourth approach: comprehensive risk factor management. Clinical outcome studies have confirmed the substantial merit of aspirin prophyllaxis and of intensive lipid-lowering therapy in secondary prevention. Prospective angiographic trials and evidence from studies of vascular biology have provided insight into mechanisms of benefit. As a consequence, lipid therapy and aspirin use have increased greatly among middle aged and older US citizens, especially those with CAD. The growth of comprehensive medical management now rivals that of invasive revascularization in secondary prevention.
We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major card... more We examined the impact of metabolic syndrome (MS) on coronary stenosis progression and major cardiovascular (CV) events and investigated the mitigating effects of low-density lipoprotein cholesterol (LDL-C) lowering and LDL-C-lowering plus high-density lipoprotein cholesterol (HDL-C) raising. This analysis combined individual patient data from 445 subjects who participated in 3 double-blinded, randomized, placebo-controlled trials (FATS, HATS, and AFREGS) comparing intensive lipid therapy to placebos on coronary stenosis progression by quantitative coronary angiography and on major CV events. The primary endpoints were the change in mean proximal coronary diameter stenosis (Δ%Sprox) over 3 years and the frequency of the pre-defined composite of coronary artery disease (CAD) death, nonfatal myocardial infarction (MI), stroke and revascularization due to worsening ischemia. Patients with the MS had 50% more rapid coronary stenosis progression and 64% increased CV event frequency compared to those without. More rapid coronary stenosis progression was significantly and independently associated with 3.5-fold increased event risk (p<0.001). Combination lipid therapy significantly decreased stenosis progression by 83% (Δ%Sprox=0.5 vs. 2.9, p<0.001) in patients with MS, and induced a small net regression in those without (Δ%Sprox=−0.3 vs. 2.0, p<0.001). Combination therapy reduced the event rate by 54% (13 vs. 28%, p=0.03) in those with MS and by 82% (3 vs. 17%, p=0.002) without. On average, each 10% reduction in LDL-C or 10% increase in HDL-C was significantly associated with 0.3 Δ%Sprox reduction. Each 10% LDL-C-lowering or 10% HDL-C-raising was associated with 11% (p=0.02) or 22% (p<0.001) event risk reduction. In conclusion, patients with MS have significantly more rapid coronary stenosis progression and a higher frequency of CV events. Greater stenosis progression rate is associated with a higher event rate. LDL-C-lowering and HDL-C-raising therapies independently and significantly decrease coronary stenosis progression and reduce CV events.
Evidence supports the idea that substantial benefits may derive from treatments that increase hig... more Evidence supports the idea that substantial benefits may derive from treatments that increase high density lipoprotein (HDL) cholesterol (HDL-C), apolipoprotein (apo) A-I, HDL2 (or 2b) or the size of HDL particles with, or without, apo A-II. HDL3 appears to be neutral in terms of coronary artery disease risk, and apo A-II appears to be adverse. Because HDL particles serve as antioxidants in vitro, the hypothesis that low HDL-C reflects an antioxidant deficiency state appears tenable. Based on these observations, a three-year angiographic study was proposed and received funding. Enrollment began in January 1995 and was completed in January 1997.
Patients with established coronary disease and abnormalities of lipid metabolism represent a part... more Patients with established coronary disease and abnormalities of lipid metabolism represent a particularly important subgroup, since their mortality risk is typically 10 times greater than that amongst-subjects with comparable risk factors but no clinical history. Such patients are commonly treated initially with anti-anginal therapy; if ischaemic symptoms persist they often undergo revascularization (bypass or angioplasty). While invasive procedures restore blood flow and relieve ischemia, they do not, in most cases, reduce risk of subsequent MI or death, or alter the underlying atherogenic process(es). Despite this, there has been a progressive 54% decline in age-adjusted cardiac mortality over the period 1960-1995, which appears best attributable to US lifestyle changes. In particular, the past decade has provided compelling evidence for the merits of a fourth approach: comprehensive risk factor management. Clinical outcome studies have confirmed the substantial merit of aspirin prophyllaxis and of intensive lipid-lowering therapy in secondary prevention. Prospective angiographic trials and evidence from studies of vascular biology have provided insight into mechanisms of benefit. As a consequence, lipid therapy and aspirin use have increased greatly among middle aged and older US citizens, especially those with CAD. The growth of comprehensive medical management now rivals that of invasive revascularization in secondary prevention.
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