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Biomedical subjects

H R Superko

Publications and source records attributed to H R Superko.

At least 19 recordsLinked to original sources
PubMed2003

Prediction of native coronary artery disease progression following PTCA or CABG in the Emory Angioplasty Versus Surgery Trial.

BACKGROUND: The natural history of atherosclerosis progression following revascularization procedures (PTCA or CABG) limits the long-term benefits of these procedures and requires continuation of risk management. MATERIAL/METHODS: Of 392 patients with multivessel disease randomized to an initial strategy of PTCA or CABG in the Emory Angioplasty Versus Surgery Trial (EAST), 298 patients (152 PTCA and 146 CABG) completed 3-year angiographic follow-up. Native coronary artery disease progression was defined as lesions with <50% diameter stenosis (%S) at baseline, measured by QCA, that increased at least 10%S to become >or=50%S during the 3-year follow-up. Major ischemic events (new Q-wave myocardial infarction, a large reversible thallium defect or additional revascularization procedures) attributed to these new lesions were determined based on the ECG ischemic changes and/or the details of the coronary anatomy. RESULTS: Of 298 patients, 53 (18%) (15% of PTCA and 21% of CABG) developed at least one significant new native coronary artery lesion. Of 136 patients with events, 19 (14%) had such events due to progression. In multivariate analysis, native coronary disease progression was independently correlated with hypertension (OR=2.4, p=0.03), ST segment depression =1mm on baseline ETT (OR=2.7, p=0.01), and percent of small LDL particles (LDL IIIa-IVb) (OR=1.2 for every 5% increase, p=0.01). CONCLUSIONS: In EAST, the native CAD progression accounted for one in seven major ischemic episodes over a 3-year follow-up. Patients with metabolic atherogenic risk profiles were more likely to have disease progression. These findings indicate the importance of more aggressive risk factor modification following revascularization.

Angiography↗
PubMed2001

Metabolic disorders contribute to subclinical coronary atherosclerosis in patients with coronary calcification.

This investigation determined the prevalence of low-density lipoprotein (LDL) subclass distribution abnormalities, elevated lipoprotein(a) (Lp(a)), and elevated total plasma homocysteine in asymptomatic subjects with subclinical coronary artery disease determined by electron beam tomography (EBT). Fifty-five percent of subjects were classified as higher risk patients and 45% as lower risk patients, employing the National Cholesterol Education Program (NCEP) lipid criteria. EBT was performed in 296 consecutive asymptomatic subjects, and blood was analyzed for total, LDL, and high-density lipoprotein (HDL) cholesterol, triglycerides, LDL subclass distribution by S(3) gradient gel electrophoresis, Lp(a), and total homocysteine. Disorders of LDL subclass distribution were the most common disorder with 60.6% of the population expressing a distribution in the small regions IIIa + IIIb of >20%; and this was more common in the NCEP higher risk group (LDL cholesterol > or =130 and/or HDL cholesterol <35 mg/dl) (p <0.0004). A Lp(a) value >25 mg/dl was found significantly more often in the NCEP higher (36.9%) compared with lower (14.3%) risk group (p <0.001). None of the laboratory measurements correlated with the calcium score or calcium score percentile rank, with the exception of a weak correlation of mean LDL peak particle diameter and calcium percentile (r = 0.14, p = 0.02). Determination of metabolic disorders in addition to LDL cholesterol and HDL cholesterol increased the diagnostic yield from 55.1%, based on NCEP lipid criteria, to 84.1% with the addition of LDL subclass distribution, Lp(a), and total homocysteine. We conclude that: (1) disorders of LDL subclass distribution and elevated Lp(a) occur frequently in NCEP higher risk patients with subclinical coronary artery disease and are the only identifiable disorders in lower NCEP risk patients; and (2) electron beam tomographic evaluation and determination of LDL subclass distribution and Lp(a) should be considered for incorporation into primary prevention guidelines.

Calcium↗
PubMed2001

Relation of coronary artery calcium identified by electron beam tomography to serum lipoprotein levels and implications for treatment.

This study was designed to determine whether the National Cholesterol Education Program (NCEP) lipid guidelines accurately identify subclinical atherosclerosis and whether low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels are related to the extent and prematurity of coronary artery disease (CAD) as determined by electron beam tomography (EBT). Out of personal concern for CAD risk, 930 consecutive asymptomatic subjects, without clinical CAD and on no lipid-lowering agents, underwent EBT. Calcium score and percentile were correlated with total cholesterol (TC), LDL-C, HDL-C, triglycerides, and demographic parameters. A calcium score of > 0 (EBT+) was found in 55% of patients; 45% of patients had a 0 score (EBT-). Mean age (58.0 +/- 10.5 vs 49.3 +/- 9.7 years, p = 0.0001), TC (218 +/- 39 vs 211 +/- 41 mg/dl, p = 0.006), LDL-C (136 +/- 36 vs 127 +/- 27 mg/dl, p = 0.005), and TC/HDL-C (4.6 +/- 1.4 vs 4.2 +/- 1.5, p = 0.0001) were significantly higher and HDL-C (52.2 +/- 17.6 vs 55.4 +/- 19.3 mg/dl, p = 0.008) lower in the EBT+ compared with EBT- group. In the EBT+ group, 75.1% of subjects had LDL-C < 160 mg/dl and would not be advised to use lipid-lowering medications according to NCEP guidelines. In subjects with LDL-C < 160 mg/dl, 51.8% of subjects were EBT+, as were 46.1% of those with LDL-C < 100 mg/dl. There were no significant differences in the calcium scores throughout the entire range of all lipid parameters; calcium percentiles were virtually identical within lipid value subgroups. We conclude that asymptomatic patients with EBT-defined subclinical atherosclerosis are not reliably identified by NCEP guidelines, and TC, LDL-C, HDL-C, TC/HDL-C, and triglyceride levels do not correlate with either the extent or prematurity of calcified plaque burden.

Analysis of Variance↗
PubMed2001

Electron beam tomography and National Cholesterol Education Program guidelines in asymptomatic women.

OBJECTIVES: This investigation was designed to determine the relationship between National Cholesterol Education Program (NCEP) ATP-II lipid guidelines and subclinical atherosclerosis, defined by electron beam tomography (EBT) calcified coronary plaque, in asymptomatic women. BACKGROUND: NCEP guidelines are used to identify women at increased risk for coronary artery disease (CAD) on the basis of low density lipoprotein cholesterol (LDLC) and high density lipoprotein cholesterol (HDLC) values. The relationship of the guidelines to subclinical atherosclerosis is unknown. METHODS: A total of 304 asymptomatic women underwent lipid and EBT evaluation and were classified as: 1) NCEP higher risk, with LDLC > or =130 mg/dl and/or HDLC <35 mg/dl, or lower risk with LDLC <130 mg/dl and HDLC > or =35 mg/dl; and 2) EBT+ if any calcified plaque was noted or EBT- if there was no calcified plaque. RESULTS: Forty-two percent of patients were EBT+, with a mean score of 227 and percentile of 73%; 58% were EBT-. Women who were EBT+ had significantly higher total cholesterol, LDLC and triglycerides than EBT- women, but only with ages < or =55 years; women >55 years demonstrated no differences. NCEP higher risk women made up 53.5% of the EBT+ and 37.7% of the EBT- groups; NCEP lower risk women accounted for 46.5% of the EBT+ and 62.3% of the EBT- groups. Assuming a higher risk in subjects with EBT-defined subclinical CAD than in those without, only 58.6% of the total group would be correctly identified by NCEP guidelines as either higher or lower risk, with correct identification of 65.5% of the younger and 52.2% of the older women. There was no correlation between either calcium percentile or score and any lipid measurement. CONCLUSIONS: This study demonstrates the shortcomings of employing NCEP guidelines to identify asymptomatic women with subclinical CAD, particularly women >55 years, and suggests increased utilization of EBT for primary prevention in the female population.

Aged↗
PubMed2000

Small, dense, low-density lipoprotein and atherosclerosis.

Disorders of low-density lipoprotein (LDL) and high- density lipoprotein (HDL) subclass distribution are more common contributors to coronary artery disease (CAD) than is elevated low-density lipoprotein cholesterol (LDLC). Recent research has emphasized the importance of LDL and HDL subclass distribution in patient management and response to treatments. Laboratory determination of LDL and HDL subclass distribution involves analytic ultracentrifugation or polyacrylalmide gradient gel electrophoresis. If subclass distribution is to be used for patient management, research quality control and standards are necessary in order to assure that the patient's values accurately reflect the metabolic disorder. The importance of this topic for patient care has been recognized by the medical insurance industry. Investigations employing electron beam computed tomography in asymptomatic individuals has revealed that 50% with established CAD have normal lipids by National Cholesterol Education Program (NCEP) criteria. However, a large proportion of other metabolic contributors to CAD are not revealed by routine blood tests.

Arteriosclerosis↗
PubMed2000

Garlic powder, effect on plasma lipids, postprandial lipemia, low-density lipoprotein particle size, high-density lipoprotein subclass distribution and lipoprotein(a).

OBJECTIVES: To test the hypothesis that a garlic supplement alters plasma lipoproteins, postprandial lipemia, low-density lipoprotein (LDL) size and high-density lipoprotein (HDL) subclass distribution differently in 50 moderately hypercholesterolemic subjects classified as LDL subclass pattern A or B. BACKGROUND: Garlic has been variably reported to reduce or not affect plasma cholesterol values. Low-density lipoprotein pattern B is a common inherited disorder of lipoprotein metabolism that has been shown to have a significantly greater response to several lipid lowering treatments including low fat diet when compared with LDL pattern A individuals. METHODS: A double blind, randomized, placebo controlled trial in an outpatient lipid research clinic was performed and included fifty moderately hypercholesterolemic subjects (mean LDL cholesterol = 166 +/- 22 mg/dl) classified as LDL subclass pattern A (predominantly large LDL, n = 22) or B (predominantly small LDL, n = 28). Following a two-month stabilization period, subjects were randomly assigned to a placebo or 300 mg three times a day of a standardized garlic tablet for three months. RESULTS: For all subjects, LDL pattern A and B subjects combined, garlic treatment for three months resulted in no significant change in total cholesterol, LDL cholesterol, HDL cholesterol, HDL subclass distribution, postprandial triglycerides, apolipoprotein B, lipoprotein (a) (Lp[a]), LDL peak particle diameter or LDL subclass distribution. There was no significant difference in response for the same parameters among subjects classified as LDL pattern A or B with the exception of significantly greater (p = 0.01) reduction in mean peak particle diameter in pattern A subjects treated with either garlic or placebo. There was no significant change in LDL subclass distribution. CONCLUSIONS: This investigation confirms that garlic therapy has no effect on major plasma lipoproteins and further, that it has no impact on HDL subclasses, Lp(a), apolipoprotein B, postprandial triglycerides or LDL subclass distribution. Garlic may have a greater effect on LDL particle diameter in LDL pattern A compared with pattern B subjects. This difference was not reflected in other plasma lipid measurements.

Biomarkers↗
PubMed1999

Small, dense low-density lipoprotein subclass pattern B: issues for the clinician.

A large portion of coronary artery disease (CAD) can be attributed to disorders of lipoprotein metabolism. However, these disorders are a complex interaction of genetic susceptibility and environmental interaction. The most common disorder of lipoprotein metabolism contributing to CAD is the Small, Dense Low-Density Lipoprotein Pattern B disorder, also known as the Atherogenic Lipoprotein Profile (ALP), which consists of multiple metabolic disorders. This disorder is an independent risk factor for CAD and in patients with established CAD, identifies a subgroup with a twofold greater rate of arteriographic progression compared with CAD patients without this disorder. Treatment of the disorder is specific to lifestyle and some pharmacologic agents. The most effective treatments are often the least expensive.

Arteriosclerosis↗
PubMed1999

Long-term blood cholesterol-lowering effects of a dietary fiber supplement.

BACKGROUND: The study evaluated the blood cholesterol-lowering effects of a dietary supplement of water-soluble fibers (guar gum, pectin) and mostly non-water-soluble fibers (soy fiber, pea fiber, corn bran) in subjects with mild to moderate hypercholesterolemia (LDL cholesterol, 3.37-4.92 mmol/L). METHODS: After stabilization for 9 weeks on a National Cholesterol Education Program Step 1 Diet, subjects were randomly assigned to receive 20 g/d of the fiber supplement (n = 87) or matching placebo (n = 82) for 15 weeks and then receive the fiber supplement for 36 weeks. The efficacy analyses included the 125 subjects (58 fiber; 67 placebo) who were treatment and diet compliant. One hundred two (52 fiber; 50 placebo) completed the 15-week comparative phase. Of these subjects 85 (45 fiber; 40 placebo) elected to continue in the 36-week noncomparative extension phase. RESULTS: The mean decreases during the 15-week period for LDL cholesterol (LDL-C), total cholesterol (TC), and LDL-C/HDL-C ratio were greater (P < 0.001) in the fiber group. The mean changes from pre-treatment values in LDL-C, TC, and LDL-C/HDL-C ratio for subjects in the fiber group were -0.51 mmol/L (-12.1%), -0.53 mmol/L (-8.5%), and -0.30 (-9.4%), respectively. The corresponding changes in the placebo group were -0.05 mmol/L (-1.3%), -0.05 mmol/L (-0.8%), and 0.05 (1.5%), respectively. The fiber supplement had no significant effects (P > 0.05) on HDL cholesterol (HDL-C), triglyceride, iron, ferritin, or vitamin A or E levels. Similar effects were seen over the subsequent 36-week noncomparative part of the study. CONCLUSIONS: The fiber supplement provided significant and sustained reductions in LDL-C without reducing HDL-C or increasing triglycerides over the 51-week treatment period.

Adolescent↗
PubMed1998

Did grandma give you heart disease? The new battle against coronary artery disease.

Atherosclerosis/coronary artery disease (CAD) is largely a result of genetically linked dyslipidemias that can often be identified in clinical practice. Expression of these genetic traits is highly individual and can be affected by environmental factors such as diet and exercise. By understanding the heterogeneity of CAD, it becomes clear that all patients cannot be optimally managed with the same therapeutic regimen. Whereas elevated low-density lipoprotein (LDL) cholesterol is strongly correlated with CAD risk, reduction of LDL cholesterol alone is not an adequate strategy in many cases. Patients with the small, dense LDL of the atherogenic lipoprotein profile (pattern B) experience a 3-fold increased risk of CAD, and pattern B is also correlated with the development of type 2 diabetes. Likewise, elevated lipoprotein(a) increases atherosclerotic risk, particularly in the presence of other risk factors, and is predictive of CAD risk in both women and men. Recent data show that the routine lipid profile--total cholesterol, triglycerides, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol--does not detect the most common inherited dyslipidemias. Newer, more sophisticated tests, such as gradient gel electrophoresis, can detect disease-relevant lipidemic details, e.g., LDL subclass pattern, LDL particle diameter, and LDL subregions. Although these testing procedures are more expensive, their cost must be weighed against the potential lifelong cost of sometimes expensive drug treatment that may be avoided based on the results of such tests. Thus, by attending to the implications of family history, the interactions of genetic, metabolic, and environmental factors, and utilizing more targeted testing procedures, physicians can match the patient's disorder with specifically effective therapy while maintaining a cost-effective approach to disease management.

Angioplasty, Balloon, Coronary↗
PubMed1998

Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia.

We performed a multicenter, open-label study to determine the long-term safety and efficacy of a new extended-release once-a-night niacin preparation, Niaspan, in the treatment of hypercholesterolemia. Niaspan, 0.5 to 3.0 g once a night at bedtime, was used alone or in combination with a statin (inhibitor of hydroxymethylglutaryl coenzyme A reductase), a bile acid sequestrant, or both. Patients included 269 hypercholesterolemic male and female adults enrolled in a 96-week study, and 230 additional adults for whom short-term safety data were available. The dosages of Niaspan attained by 269 patients were 1,000 mg (95% of patients), 1,500 mg (86%), and 2,000 mg (65%). After 48 weeks of treatment, Niaspan alone (median dose 2,000 mg) reduced low-density lipaprotein (LDL) cholesterol (18%), apolipoprotein B (15%), total cholesterol (11%), triglycerides (24%), and lipoprotein(a) (36%), and increased high-density lipoprotein (HDL) cholesterol (29%). Niaspan plus a statin lowered LDL cholesterol (32%), apolipoprotein B (26%), total cholesterol (23%), triglycerides (30%), and lipoprotein(a) (19%), and increased HDL cholesterol (26%). Reversible elevations of aspartate aminotransferase or alanine aminotransferase more than twice the normal range occurred in 2.6% of patients. One patient discontinued Niaspan because of transaminase elevations. Intolerance to flushing, leading to discontinuation of Niaspan, occurred in 4.8% of patients. The overall rate of discontinuance due to flushing in this study combined with 2 previous randomized trials was 7.3%. In the long-term treatment of hypercholesterolemia, Niaspan produced favorable changes in LDL and HDL cholesterol, triglycerides, and lipoprotein(a). Adverse hepatic effects were minor and occurred at rates similar to those reported for statin therapy.

Adult↗
PubMed1998

Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia.

This study compared the efficacy and safety of a once-a-night, time-release niacin formulation, Niaspan (Kos Pharmaceuticals, Miami Lakes, FL), with plain niacin and placebo for the treatment of primary hypercholesterolemia. The study was conducted in nine academic lipid research clinics in a randomized, double-blind design. Niaspan 1.5 g at bedtime was compared with plain niacin 1.5 g/d after 8 weeks and 3.0 g/d after 16 weeks in divided doses and with placebo. A total of 223 hypercholesterolemic adult men and women participated. Compared with placebo at 8 weeks, Niaspan versus plain niacin at 1.5 g/d showed comparable efficacy, comparably lowering total cholesterol (C) (8%/8%), triglycerides (16%/18%), low-density lipoprotein (LDL)-C (12%/12%), apolipoprotein (apo B) (12%/12%), apo E (9%/7%), and lipoprotein(a) [Lp(a)] (15%/11%), and raising high-density lipoprotein (HDL)-C (20%/17%), HDL2-C (37%/33%), HDL3-C (17%/16%), and apo A-I (8%/6%) (P < or = .05 in all instances). After 16 weeks, the Niaspan effect on LDL-C and triglyceride was unchanged while the plain niacin effect approximately doubled. At equal doses of 1.5 g/d of Niapan versus plain niacin, respectively, AST increased 5.0% versus 4.8% (difference not significant [NS]), fasting plasma glucose increased 4.8% versus 4.5% (NS), and uric acid concentrations increased less, 6% versus 16% (P=.0001). Flushing events were more frequent with plain niacin versus Niaspan (1,905 v 576, P < .001). Flushing severity was slightly greater with Niaspan, but still well tolerated. In conclusion, Niaspan 1.5 g hour of sleep (hs) has comparable efficacy, a lower incidence of flushing, a lesser uric acid rise, and an equivalent hepatic enzyme effect than 500 mg thrice-daily plain niacin in hyperlipidemic subjects. Niaspan may be an equivalent or better alternative to plain niacin at moderate doses in the management of hyperlipidemia.

Double-Blind Method↗
PubMed1997

Effect of fluvastatin on low-density lipoprotein peak particle diameter.

The effect of fluvastatin on low-density lipoprotein (LDL) particle diameter was investigated in 42 hypercholesterolemic patients. Fluvastatin reduced LDL cholesterol significantly but had no effect on LDL particle diameter; it also had no differential effect on patients classified as LDL pattern A (large LDL), pattern B (small LDL), or I (intermediate LDL).

Analysis of Variance↗
PubMed1997

The new thinking on lipids and coronary artery disease.

Detection and treatment of high blood cholesterol has significantly reduced cardiovascular events. However, most individuals with coronary artery disease do not have hypercholesterolemia. Atherosclerosis is a complex interaction of inherited susceptibility and environmental issues that combine to create an atherogenic milieu. Appropriate diagnosis and treatment of patients with coronary artery disease can be of significant benefit, but if treatment is not individualized to the patient's individual metabolic abnormality, many patients will receive little to no benefit despite improved lipid profiles.

Cholesterol↗
PubMed1996

Cost-effective treatment of coronary artery disease--the new imperative.

Large lipid-lowering clinical trials have demonstrated a significant reduction in cardiovascular events and the need for cardiovascular procedures. These clinical and point trials used relatively weak treatment modalities, and when the cost savings of the reduced number of events is balanced against the estimated cost of treatment, the average difference is approximately $1,500 per patient per year. Arteriographic trials have used similar or more aggressive lipoprotein therapy over shorter periods of time. Estimates of cost savings from reduced clinical events balanced against the cost of treatment in these studies indicate a wide spectrum of estimated patient costs. These estimates range between a cost of $2,273 per patient per year to a cost savings of (-)$901 per patient per year. Extrapolation to the United States population with coronary artery disease (CAD) suggests that greater than one billion dollars per year could be saved if patients with CAD received similar treatment and responded in a similar manner.

Cholesterol, HDL↗