Biomedical subjects
Publications and source records attributed to H R Superko.
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The small LDL pattern B trait, and triglyceride rich lipoproteins, have now been established as major coronary heart disease risk factors and have been associated with its severity. The presence of these disorders identifies a patient subgroup which is at substantial coronary artery disease risk but also exhibits the best arteriographic response to treatment. Most lipid-lowering treatments have a differential effect in LDL subclass pattern A patients compared with those with pattern B that helps explain the differential arteriographic response seen in clinical trials.
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The risk factors for coronary artery disease have been expanded in recent years to include several clinically significant metabolic disorders. The small, dense low-density lipoprotein trait is one of the most common inherited coronary artery disease risk factors and recent reports describe the clinical use of low-density lipoprotein phenotyping for coronary artery disease risk determination, and for treatment in patients with established disease. Apolipoprotein E isoforms play a role in diet responsiveness and may explain approximately 12% of cases of myocardial infarction. Hypoalphalipoproteinemia appears to be a spectrum of overlapping disorders and is difficult to treat. Low-density lipoprotein oxidation may be affected by dietary sources of oxidized fat, and a recent antioxidation trial reported negative results. In the past year, homocyst(e)inemia was reported to play a significant role in coronary artery disease risk prediction and lipoprotein(a) phenotypes appear to clarify the risk of lipoprotein(a).
Large clinical trials involving lipoprotein therapy and clinical end-points or arteriographic change have demonstrated a significant reduction in cardiovascular events and the need for cardiovascular procedures. Clinical end-point trials that used relatively weak treatment modalities have resulted in reduced clinical events and when the cost savings of the reduced number of events is balanced against the cost of treatment, the average difference is approximately US$1,500/patient/year. Arteriographic trials have used similar or more aggressive lipoprotein therapy over shorter periods of time. Similar estimates of cost savings from reduced clinical events balanced against the cost of treatment indicates a wide spectrum of estimated patient costs. These estimates range between a cost of $2,273/patient/year, to a cost savings of -$901/patient/year. Extrapolation to the United States population with coronary artery disease (CAD) suggests that greater than $1 billion per year could be saved if CAD patients received similar treatment and responded in a similar manner.
Recent advances in lipidology and metabolic aspects of atherosclerosis allow detailed coronary artery disease (CAD) risk assessment that is of clinical relevance. Genetic dyslipidemias can be identified in over 75% of CAD patients and include the atherosclerosis susceptibility trait (low density lipoprotein [LDL] pattern B), hyperapobetalipoproteinemia, lipoprotein (a), apo E isoforms, and lipoprotein susceptibility to oxidative damage. The inherited amino acid disorder homocysteinemia is present in approximately 20% of CAD patients and is easily treated. Recent studies have highlighted significant differences in response to diet and drug therapy that can be predicted based on the presence or absence of these traits.
Physical activity can have a significant effect on plasma lipoproteins and lipoprotein metabolism. The effect of exercise on lipoprotein subclasses is often more significant than is reflected by routine measures of lipoprotein cholesterol. These effects have important clinical implications. Some apolipoprotein levels, with the exception of those of lipoprotein (a), are affected by physical activity. Changes in enzymes, as well as transfer protein, activity can help explain the exercise-induced changes in lipoprotein levels. Understanding the complex interaction between exercise and lipoprotein metabolism will enable the therapeutic use of exercise in the appropriate patient population.
OBJECTIVE: To evaluate the efficacy of a physician-directed, nurse-managed, home-based case-management system for coronary risk factor modification. DESIGN: Randomized clinical trial in which patients received a special intervention (n = 293) or usual medical care (n = 292) during the first year after acute myocardial infarction. SETTING: 5 Kaiser Permanente Medical Centers in the San Francisco Bay area. PATIENTS: 585 men and women aged 70 years or younger who were hospitalized for acute myocardial infarction. INTERVENTION: In the hospital, specially trained nurses initiated interventions for smoking cessation, exercise training, and diet-drug therapy for hyperlipidemia. Intervention after discharge was implemented primarily by telephone and mail contact with patients in their homes. All medically eligible patients received exercise training; all smokers received the smoking cessation intervention; and all patients received dietary counseling and, if needed, lipid-lowering drug therapy. OUTCOME: Smoking prevalence and plasma low-density lipoprotein cholesterol (LDL) concentrations were measured 2 months after infarction, and functional capacity was measured 6 months after infarction. RESULTS: In the special intervention and usual care groups, the cotinine-confirmed smoking cessation rates were 70% and 53% (P = 0.03), plasma LDL cholesterol levels were 2.77 +/- 0.69 mmol/L and 3.41 +/- 0.90 mmol/L (107 +/- 30 mg/dL and 132 +/- 30 mg/dL) (P = 0.001), and functional capacities were 9.3 +/- 2.4 METS and 8.4 +/- 2.5 METS (P = 0.001), respectively. CONCLUSION: In a large health maintenance organization, a case-management system was considerably more effective than usual medical care for modification of coronary risk factors after myocardial infarction.
Coffee consumption has been weakly linked to high blood pressure (BP). The hypothesis that cessation of caffeinated-coffee consumption lowers ambulatory BP was tested in men in a randomized trial. One hundred eighty-six middle-aged, normotensive, male, habitual caffeinated-coffee consumers were recruited. Of these subjects, 150 had sufficiently complete, ambulatory BP measurements for analysis. After 2 months of standard caffeinated-coffee consumption, subjects were randomized to consume an equal amount of the same standard caffeinated coffee or a standard decaffeinated coffee, or to discontinue coffee consumption for 2 months. Diet composition, body weight and exercise did not change. Resting BP and heart rate were not different between the groups before and after intervention. In comparison with the continued caffeinated-coffee group (control), the decaffeinated-coffee group revealed significant reductions in mean ambulatory systolic BP during the morning (-4.0 +/- 11 mm Hg; p = 0.014), afternoon (-5.3 +/- 10 mm Hg; p = 0.001) and evening (-3.2 +/- 10 mm Hg; p = 0.003) hours, reductions in mean ambulatory diastolic BP during the afternoon (-1.8 +/- 10 mm Hg; p = 0.063) and evening (-1.8 +/- 10 mm Hg; p = 0.059) hours and no change in ambulatory heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Recent clinical trials have shown that modification of plasma lipoprotein concentrations can favorably alter progression of coronary atherosclerosis, but no data exist on the effects of a comprehensive program of risk reduction involving both changes in lifestyle and medications. This study tested the hypothesis that intensive multiple risk factor reduction over 4 years would significantly reduce the rate of progression of atherosclerosis in the coronary arteries of men and women compared with subjects randomly assigned to the usual care of their physician. METHODS AND RESULTS: Three hundred men (n = 259) and women (n = 41) (mean age, 56 +/- 7.4 years) with angiographically defined coronary atherosclerosis were randomly assigned to usual care (n = 155) or multifactor risk reduction (n = 145). Patients assigned to risk reduction were provided individualized programs involving a low-fat and -cholesterol diet, exercise, weight loss, smoking cessation, and medications to favorably alter lipoprotein profiles. Computer-assisted quantitative coronary arteriography was performed at baseline and after 4 years. The main angiographic outcome was the rate of change in the minimal diameter of diseased segments. All subjects underwent medical and risk factor evaluations at baseline and yearly for 4 years, and reasons for all hospitalizations and deaths were documented. Of the 300 subjects randomized, 274 (91.3%) completed a follow-up arteriogram, and 246 (82%) had comparative measurements of segments with visible disease at baseline and follow-up. Intensive risk reduction resulted in highly significant improvements in various risk factors, including low-density lipoprotein cholesterol and apolipoprotein B (both, 22%), high-density lipoprotein cholesterol (+12%), plasma triglycerides (-20%), body weight (-4%), exercise capacity (+20%), and intake of dietary fat (-24%) and cholesterol (-40%) compared with relatively small changes in the usual-care group. No change was observed in lipoprotein(a) in either group. The risk-reduction group showed a rate of narrowing of diseased coronary artery segments that was 47% less than that for subjects in the usual-care group (change in minimal diameter, -0.024 +/- 0.066 mm/y versus -0.045 +/- 0.073 mm/y; P < .02, two-tailed). Three deaths occurred in each group. There were 25 hospitalizations in the risk-reduction group initiated by clinical cardiac events compared with 44 in the usual-care group (rate ratio, 0.61; P = .05; 95% confidence interval, 0.4 to 0.9). CONCLUSIONS: Intensive multifactor risk reduction conducted over 4 years favorably altered the rate of luminal narrowing in coronary arteries of men and women with coronary artery disease and decreased hospitalizations for clinical cardiac events.
BACKGROUND: Numerous reports suggest that coronary artery disease can regress with lipoprotein manipulation. Many of these reports lack control groups and contain relatively small numbers. METHODS AND RESULTS: Ten randomized controlled clinical trials using coronary arteriography to assess the effect of lipoprotein manipulation on the rate of progression and regression of atherosclerosis have been either published or reported as an abstract at a national meeting. These studies were critically reviewed for individual differences and combined clinically applicable lessons. These trials involved a total of 2095 subjects and have consistently reported reduction in the percentage of patients arteriographically defined as progressing (mean, 23.6%) and an increase in the percentage regressing (mean, 20.0%) compared with control groups. Compared with large clinical trials using clinical end points, lipoprotein change was greater, achieving on average a 28% reduction in low-density lipoprotein cholesterol, 11% reduction in triglycerides, and 11% increase in high-density lipoprotein cholesterol compared with control groups. Four investigations used a nonpharmacological approach, and seven used single and multiple drug therapy combined with diet. Despite the relatively brief treatment time of often 2 to 4 years, clinical events were fewer in the treatment groups; within some studies, this reached statistical significance. Side effects from the different therapies were tolerated by most patients, and severe adverse clinical events were few. CONCLUSIONS: These trials present convincing evidence that aggressive lipoprotein manipulation can result in improved arteriographic measurements and fewer cardiovascular events in a relatively short period of time of 2 to 4 years. Extrapolation of this information to the larger population with known coronary artery disease suggests that directed lipoprotein manipulation can reduce clinical events in a cost-effective manner.
The relationship of beta-blocker drug use to plasma low density lipoprotein-cholesterol (LDL-C), lipoprotein mass distribution, (LDL, Sf0-12), intermediate density lipoproteins (IDL, Sf12-20), very low density lipoproteins (VLDL, Sf20-400), and high density lipoproteins (HDL, F(1.2)0-9) were examined in 206 men with coronary heart disease. Thirty-three used non-selective (NSEL), 49 used selective (SEL), and were compared to 124 who used no beta-blockade (NoBB). No significant between group differences were seen for potentially confounding variables. LDL and IDL mass, total cholesterol and LDL-cholesterol were not significantly different between groups. HDL-C was significantly lower in both NSEL (P < 0.005) and SEL (P < 0.01). NSEL and SEL had significantly lower HDL mass (P < 0.005 and P < 0.005) and SEL (P < 0.01 and P = 0.06), and HDL3 mass (P < 0.01 and P < 0.05). VLDL mass was significantly higher (P < 0.02) only in NSEL. Small LDL (Sf0-7) was not significantly different between groups and large LDL (Sf7-12) was significantly lower in NSEL (P < 0.05) and SEL (P < 0.05). LDL peak Sf was significantly lower in both NSEL (P < 0.005) and SEL (P < 0.02) compared to NoBB. Despite the lack of differences in levels of LDL-cholesterol, beta-blocker use is associated with a significant difference in the distribution of larger, more buoyant to smaller, more dense LDL particles. Reduced HDL levels in subjects on beta-blockade therapy are associated with reductions in both HDL2 and HDL3 subclasses.(ABSTRACT TRUNCATED AT 250 WORDS)
Recommended doses of bile-acid binding resins have an established hypocholesterolemic effect, but data on responses to low doses, especially in women and subjects with moderate hypercholesterolemia, are sparse. A double-blind, placebo-controlled, randomized trial of 3 low doses of colestipol hydrochloride was conducted in women and men with moderate hypercholesterolemia. Men and women with plasma low-density lipoprotein (LDL) cholesterol concentrations greater than 4 mmol/liter (155 mg/dl) and triglyceride concentrations less than 2.82 mmol/liter (250 mg/dl) were recruited for the study. Eligible patients (54 women and 98 men) were placed on the American Heart Association step I diet 6 weeks before randomization. Participants were subsequently assigned to 1 of 4 drug treatment groups (placebo, and 5, 10 and 15 g/day of colestipol in 2 divided doses) for an additional 12 weeks. Of the 152 patients randomized, 141 completed all aspects of the study. For the treatment groups--placebo, and 5, 10 and 15 g of colestipol--LDL cholesterol reductions (mmol/liter) were observed respectively (n = 141): 0.10 +/- 0.49 (2.7%), 0.65 +/- 0.41 (16.3%), 0.98 +/- 0.36 (22.8%) and 1.17 +/- 0.47 (27.2%) (p less than 0.001). Similar changes were observed in total cholesterol and apolipoprotein B concentrations. The apolipoprotein B/LDL cholesterol ratio increased significantly with increasing colestipol dosage. Modest but insignificant changes in plasma triglyceride levels occurred, and high-density lipoprotein cholesterol levels remained unchanged. A dose of 5 g/day of colestipol achieved 51% of the LDL cholesterol reduction noted with 15 g/day. Low-dose colestipol therapy is effective in the treatment of patients with moderate hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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Twenty-six subjects (20 male, 6 female) at high risk for CAD events were treated with moderate doses of nicotinic acid to investigate whether there was a differential lipoprotein response in patients with different LDL subclass patterns. Subjects were selected to have either pattern A (predominance of large LDL, peak particle diameter greater than 262 A, n = 9) or pattern B (predominance of small LDL, peak particle diameter less than 255 A, n = 17) as assessed by 2-16% gradient gel electrophoresis of plasma. Nicotinic acid dose was similar in pattern A (2111 +/- 651 mg/day) and pattern B subjects (1875 +/- 698 mg/day). Total cholesterol and LDL cholesterol decreased by similar amounts in pattern A (-41 +/- 26 mg/dl and -37 +/- 18 mg/dl) and pattern B (-51 +/- 44 mg/dl and -44 +/- 45 mg/dl) subjects. Triglycerides tended to be reduced more in pattern B subjects (-100 +/- 175 mg/dl) compared to pattern A subjects (-23 +/- 34 mg/dl) although this difference was not statistically significant (P = 0.08 for triglycerides log transformed). HDL cholesterol increased significantly more in the pattern B group (11.9 +/- 14.2 mg/dl) compared to pattern A subjects (0.7 +/- 8.5 mg/dl), (P less than 0.04). Similarly, LDL particle diameter increased significantly more in the pattern B subjects (9.8 +/- 6.9 A) compared to the pattern A subjects (3.6 +/- 3.0 A), (P less than 0.02). All pattern B subjects who achieved a plasma triglyceride less than 140 mg/dl converted to pattern A.(ABSTRACT TRUNCATED AT 250 WORDS)
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Coffee consumption has been associated with elevated plasma cholesterol. One hundred eighty-one men consumed a standard caffeinated coffee for 2 mo followed by randomization to continue caffeinated coffee (control), change to decaffeinated coffee or no coffee for 2 mo. Plasma low-density-lipoprotein (LDL) cholesterol and apolipoprotein B concentrations increased significantly (0.12 +/- 0.65 mmol/L, P less than 0.025; 0.06 +/- 0.12 g/L, P less than 0.0004, respectively) in the group that changed to decaffeinated coffee. In a subgroup (n = 51), post-heparin lipoprotein lipase decreased significantly more (-270 mmol free fatty acids.L-1.h-1, P less than 0.003) in the decaffeinated-coffee group. Resting heart rate and blood pressure did not change significantly. Change from caffeinated to decaffeinated coffee increased plasma LDL cholesterol and apolipoprotein B whereas discontinuation of caffeinated coffee revealed no change. This finding suggests that a coffee component other than caffeine is responsible for the LDL cholesterol, apolipoprotein B, and lipase activity changes reported in this investigation.