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Biomedical subjects

F M Sacks

Publications and source records attributed to F M Sacks.

At least 19 recordsLinked to original sources

Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment: individual patient meta-analysis of 13,677 subjects.

BACKGROUND: Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated between this genetic variant and pravastatin treatment, but this has not been confirmed. METHODS AND RESULTS: A meta-analysis was performed on individual patient data from 7 large, population-based studies (each >500 individuals) and 3 randomized, placebo-controlled, pravastatin trials. Linear and logistic regression models were used to assess the relation between TaqIB genotype and HDL-C levels and CAD risk. After adjustment for study, age, sex, smoking, body mass index (BMI), diabetes, LDL-C, use of alcohol, and prevalence of CAD, TaqIB genotype exhibited a highly significant association with HDL-C levels, such that B2B2 individuals had 0.11 mmol/L (0.10 to 0.12, P<0.0001) higher HDL-C levels than did B1B1 individuals. Second, after adjustment for study, sex, age, smoking, BMI, diabetes, systolic blood pressure, LDL-C, and use of alcohol, TaqIB genotype was significantly associated with the risk of CAD (odds ratio=0.78 [0.66 to 0.93]) in B2B2 individuals compared with B1B1 individuals (P for linearity=0.008). Additional adjustment for HDL-C levels rendered a loss of statistical significance (P=0.4). Last, no pharmacogenetic interaction between TaqIB genotype and pravastatin treatment could be demonstrated. CONCLUSIONS: The CETP TaqIB variant is firmly associated with HDL-C plasma levels and as a result, with the risk of CAD. Importantly, this CETP variant does not influence the response to pravastatin therapy.

Cardiovascular Diseases↗

The relative role of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in coronary artery disease: evidence from large-scale statin and fibrate trials.

Statin therapy has been remarkably successful in reducing coronary events and improving survival. Reduction in low-density lipoprotein cholesterol (LDL-C) is the paramount mechanism for the benefit of statins. Although the relation between reduction of risk of coronary artery disease and pretreatment lipid levels has not been fully resolved, a feature of statin therapy emerging from previous large-scale trials is the diminished benefit when the baseline level of LDL-C is low (eg, <125 mg/dL). Increases in levels of high-density lipoprotein cholesterol (HDL-C) with statin therapy are associated with mild reductions in coronary events, indicating that HDL-C is an important element. However, the risk of low HDL-C is not altered by statin therapy, in marked contrast with LDL-C. Because most coronary events have not been prevented in the statin trials, nonstatin lipid therapy, including fibrates, may be necessary to further reduce the unacceptably high rate of coronary artery disease.

Anticholesteremic Agents↗

Effects of diet and sodium intake on blood pressure: subgroup analysis of the DASH-sodium trial.

BACKGROUND: Initial findings from the Dietary Approaches to Stop Hypertension (DASH)-Sodium Trial demonstrated that reduction of sodium intake in two different diets decreased blood pressure in participants with and without hypertension. OBJECTIVE: To determine effects on blood pressure of reduced sodium intake and the DASH diet in additional subgroups. DESIGN: Randomized feeding study. SETTING: Four clinical centers and a coordinating center. PARTICIPANTS: 412 adults with untreated systolic blood pressure of 120 to 160 mm Hg and diastolic blood pressure of 80 to 95 mm Hg. INTERVENTION: Participants followed the DASH diet or a control (typical U.S.) diet for three consecutive 30-day feeding periods, during which sodium intake (50, 100, and 150 mmol/d at 2100 kcal) varied according to a randomly assigned sequence. Body weight was maintained. MEASUREMENTS: Systolic and diastolic blood pressure. RESULTS: In all subgroups, the DASH diet and reduced sodium intake were each associated with significant decreases in blood pressure; these two factors combined produced the greatest reductions. Among nonhypertensive participants who received the control diet, lower (vs. higher) sodium intake decreased blood pressure by 7.0/3.8 mm Hg in those older than 45 years of age (P < 0.001) and by 3.7/1.5 mm Hg in those 45 years of age or younger (P < 0.05). CONCLUSION: The DASH diet plus reduced sodium intake is recommended to control blood pressure in diverse subgroups.

Adult↗

Low-density lipoprotein size, pravastatin treatment, and coronary events.

CONTEXT: Small low-density lipoprotein (LDL) particle size has been hypothesized to be a risk factor for coronary heart disease (CHD). Animal models link large LDL to atherosclerosis. However, the strong association between small LDL and other risk factors, particularly triglyceride levels, impedes determining whether LDL size independently predicts CHD in humans. OBJECTIVE: To examine whether LDL size is an independent predictor of recurrent coronary events in patients with known CHD, as opposed to a marker for other lipid abnormalities. DESIGN AND SETTING: Prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin conducted in 1989-1996. PARTICIPANTS: Survivors of myocardial infarction with typical LDL concentrations (416 cases and 421 controls). MAIN OUTCOME MEASURE: Subsequent myocardial infarction or coronary death during the 5-year follow-up, analyzed by quintile of LDL particle size and by treatment group. RESULTS: Overall, the mean LDL size was identical in cases and controls (25.6 nm). In patients in the placebo group, large LDL predicted coronary events in models adjusted only for age (relative risk [RR], 1.79; 95% confidence interval [CI], 1.01-3.17) and for age and lipid and nonlipid risk factors (RR, 4.00; 95% CI, 1.81-8.82), comparing those in the highest (mean, 26.6 nm) and lowest (mean, 24.5 nm) quintiles of LDL size. This increased risk was not present in those taking pravastatin (age-adjusted analysis: RR, 0.98; 95% CI, 0.47-2.04; P =.046 for interaction for a difference in the effect of LDL size on coronary events between the placebo and treatment groups; multivariable analysis: RR, 1.33; 95% CI, 0.52-3.38; P =.11 for interaction). CONCLUSIONS: Large LDL size was an independent predictor of coronary events in a typical population with myocardial infarction, but the adverse effect was not present among patients who were treated with pravastatin. Identifying patients on the basis of LDL size may not be useful clinically, since effective treatment for elevated LDL cholesterol concentrations also effectively treats risk associated with large LDL.

Anticholesteremic Agents↗

The platelet Pl(A2) and angiotensin-converting enzyme (ACE) D allele polymorphisms and the risk of recurrent events after acute myocardial infarction.

Chromosome 17q21-23 harbors genes for platelet glycoprotein IIIa and angiotensin-converting enzyme (ACE), which are polymorphic for alleles Pl(A2) and ACE "D." These alleles have been independently and often associated with ischemic coronary artery disease (CAD). We sought to determine if the Pl(A2) and ACE D polymorphisms were risk factors for recurrent coronary events. In the Cholesterol And Recurrent Events (CARE) trial, 4,159 men and women with documented myocardial infarction (MI) were randomized to receive either placebo or pravastatin, and were followed prospectively for 5 years. Pl(A) and ACE genotypes were determined in 767 patients: 385 cases who had experienced a recurrent primary event (death due to coronary disease or nonfatal MI), and 382 age- and gender-matched controls. In patients receiving placebo, the Pl(A1,A2) genotype conferred a relative risk (RR) of 1.38 (confidence intervals [CI] 1.04 to 1.83; p = 0.028; adjusted RR = 1.32, CI = 0.99 to 1.76; p = 0.058]) for the primary end point. Compared with the placebo group, pravastatin reduced the excess RR of coronary disease death and recurrent MI in the Pl(A1,A2) patient population by 31% (p = 0.06). The ACE D allele appeared to have modestly additive effects on the Pl(A1,A2) risk. Among the Pl(A1,A2) patients, pravastatin had little effect on the risk of recurrent events with the ACE II genotype, but reduced the adjusted RR from 1.42 (placebo) to 0.58 for ACE ID patients, and from 1.56 (placebo) to 0.83 for ACE DD. The Pl(A1,A2) genotype was associated with an excess of recurrent coronary events in patients after MI who did not receive pravastatin, and the ACE D allele added to this risk. These data suggest that it would be important to perform a larger study to address the potential role of these genotypes in therapeutic decision making.

Aged↗

Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group.

BACKGROUND: The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension. METHODS: A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order. RESULTS: Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P=0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during the DASH diet (P<0.01). The effects of sodium were observed in participants with and in those without hypertension, blacks and those of other races, and women and men. The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level; and the difference was greater with high sodium levels than with low ones. As compared with the control diet with a high sodium level, the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension, and 11.5 mm Hg lower in participants with hypertension. CONCLUSIONS: The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially, with greater effects in combination than singly. Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods.

Blood Pressure↗

Cost-effectiveness of pravastatin therapy for survivors of myocardial infarction with average cholesterol levels.

BACKGROUND: The objective of this study was to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infarction with average cholesterol levels. METHODS: We performed a cost-effectiveness analysis based on actual clinical, cost, and health-related quality-of-life data from the Cholesterol and Recurrent Events (CARE) trial. Survival and recurrent coronary heart disease events were modeled from trial data in Markov models, with the use of different assumptions regarding the long-term benefit of therapy. RESULTS: Pravastatin therapy increased quality-adjusted life expectancy at an incremental cost of $16,000 to $32,000 per quality-adjusted life-year gained. In subgroup analyses, the cost-effectiveness of pravastatin therapy was more favorable for patients >60 years of age and for patients with pretreatment low-density lipoprotein cholesterol levels >125 mg/dL. Results were sensitive to the cost of pravastatin and to assumptions about long-term survival benefits from pravastatin therapy. CONCLUSIONS: The cost-effectiveness of pravastatin therapy in survivors of myocardial infarction with average cholesterol levels compares favorably with other interventions.

Anticholesteremic Agents↗

Effects on blood lipids of a blood pressure-lowering diet: the Dietary Approaches to Stop Hypertension (DASH) Trial.

BACKGROUND: Effects of diet on blood lipids are best known in white men, and effects of type of carbohydrate on triacylglycerol concentrations are not well defined. OBJECTIVE: Our goal was to determine the effects of diet on plasma lipids, focusing on subgroups by sex, race, and baseline lipid concentrations. DESIGN: This was a randomized controlled outpatient feeding trial conducted in 4 field centers. The subjects were 436 participants of the Dietary Approaches to Stop Hypertension (DASH) Trial [mean age: 44.6 y; 60% African American; baseline total cholesterol: < or = 6.7 mmol/L (< or = 260 mg/dL)]. The intervention consisted of 8 wk of a control diet, a diet increased in fruit and vegetables, or a diet increased in fruit, vegetables, and low-fat dairy products and reduced in saturated fat, total fat, and cholesterol (DASH diet), during which time subjects remained weight stable. The main outcome measures were fasting total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol. RESULTS: Relative to the control diet, the DASH diet resulted in lower total (-0.35 mmol/L, or -13.7 mg/dL), LDL- (-0.28 mmol/L, or -10.7 mg/dL), and HDL- (-0.09 mmol/L, or -3.7 mg/dL) cholesterol concentrations (all P < 0.0001), without significant effects on triacylglycerol. The net reductions in total and LDL cholesterol in men were greater than those in women by 0.27 mmol/L, or 10.3 mg/dL (P = 0.052), and by 0.29 mmol/L, or 11.2 mg/dL (P < 0.02), respectively. Changes in lipids did not differ significantly by race or baseline lipid concentrations, except for HDL, which decreased more in participants with higher baseline HDL-cholesterol concentrations than in those with lower baseline HDL-cholesterol concentrations. The fruit and vegetable diet produced few significant lipid changes. CONCLUSIONS: The DASH diet is likely to reduce coronary heart disease risk. The possible opposing effect on coronary heart disease risk of HDL reduction needs further study.

Adult↗

Angiotensinogen genotype and blood pressure response in the Dietary Approaches to Stop Hypertension (DASH) study.

OBJECTIVE: To determine the relationship between angiotensinogen (ANG) genotype and blood pressure response to the dietary patterns of the Dietary Approaches to Stop Hypertension (DASH) trial. The angiotensin converting enzyme (ACE) gene was also tested. DESIGN: The DASH trial was a randomized outpatient feeding study comparing the effects on blood pressure (BP) of three dietary patterns: a control diet, similar to typical American intake; a 'fruits and vegetables' diet (F/V) that is rich in fruits and vegetables but otherwise resembles the control diet; and the DASH diet that is reduced in fats and that emphasizes fruits, vegetables and low-fat dairy products. Participants' genotype was also determined. SETTING: Four clinical sites. PARTICIPANTS: Adults with above-optimal BP or stage 1 hypertension. INTERVENTION: Participants ate one of the three dietary patterns for 8 weeks. Sodium intake and weight were held constant. In 355 of 459 DASH participants, DNA was extracted from leukocytes and genotyped for the G-6A ANG polymorphism and the D/I ACE polymorphism, by the polymerase chain reaction. MAIN OUTCOMES: Genotype at ANG and ACE loci; BP after 8 weeks of intervention diet. RESULTS: There was no association between ACE genotype and BP response. Associations with ANG polymorphism were significant: net systolic and diastolic BP response to the DASH diet was greatest in individuals with the AA genotype (-6.93/-3.68 mmHg) and least in those with the GG genotype (-2.80/0.20 mmHg). A similar relationship existed for the F/V diet. CONCLUSIONS: ANG genotype is associated with BP response to the DASH diet. The AA genotype confers excess risk of hypertension and is associated with increased responsiveness to diet.

Adult↗

Differential metabolism of human VLDL according to content of ApoE and ApoC-III.

We studied the metabolism of very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) particles that did or did not have apolipoprotein E (apoE) in 12 normolipidemic women by endogenously labeling plasma apolipoprotein B. The plasma was separated into bound (E+) and unbound (E-) fractions by use of a monoclonal antibody (1D7), and the fractions were ultracentrifuged to yield E+ and E- subfractions of light and dense VLDL and IDL. VLDL E+ and IDL E+ were produced mainly by the liver. VLDL E+ and IDL E+ had lower fractional catabolic rates and much higher apolipoprotein C-III (apoC-III) content than did the corresponding E- particles. Most light VLDL apoE+ underwent lipolysis to dense VLDL E+ with reduced apoC-III content, which was removed from the circulation without conversion to IDL. In contrast, most light VLDL apoE-, poor in apoC-III, was removed from the circulation, and a smaller proportion underwent lipolysis to dense VLDL E-. Most dense VLDL E- underwent lipolysis to IDL E-. The rate constant for lipolysis of dense VLDL to IDL was greater for E- than for E+, and the rate constant for clearance from plasma was greater for dense VLDL E+ than for E-. In conclusion, metabolism of human VLDL particles is influenced by their content of apoE, further modulated by the coexistence of apoC-III.

Aged↗

Threshold level or not for low-density lipoprotein cholesterol.

As drugs, such as the statins, and other therapies demonstrate the ability to significantly lower levels of low-density lipoprotein cholesterol (LDL-C), one issue is whether there is a lower threshold below which no further decline in coronary heart disease occurs. Those who evaluate the data from multiple trials and conclude that no significant decrease in coronary event rates occurs at or below 125 mg/dL suggest using this level as a guideline for clinical application of cholesterol-lowering therapy. On the other hand, analysis of the results of the same population and primary prevention studies concludes that no such threshold exists. The issues affected by the decision of whether to use a threshold include costs to the healthcare system for additional physician time, tests, and medication; unknown clinical events and safety related to very low LDL-C; and resource prioritization to an unestablished therapeutic approach.

Anticholesteremic Agents↗

Distinct patterns of lipoproteins with apoB defined by presence of apoE or apoC-III in hypercholesterolemia and hypertriglyceridemia.

Apolipoprotein (apo) E and apoC-III concentrations in VLDL and LDL are associated with coronary heart disease. We studied the relationship between apoE and apoC-III and the abnormal concentrations and distribution of apoB lipoproteins in 10 hypercholesterolemic and 13 hypertriglyceridemic patients compared with 12 normolipidemic subjects (mean age, 45 years). Sixteen distinct types of apoB lipoprotein particles were separated by first using anti-apoE and anti-apoC-III immunoaffinity chromatography in sequence and then ultracentrifugation [light VLDL, dense VLDL, IDL, and LDL, with apoE with or without apoC-III (E(+)C-III(+), E(+)C-III(-)) or without apoE with or without apoC-III (E(-)C-III(+), E(-)C-III(-))]. The concentrations of VLDL particles with apoC-III (E(+)C-III(+), E(-)C-III(+)) were increased in the hypertriglyceridemic group compared with the hypercholesterolemic and normolipidemic groups. These particles were the most triglyceride rich of the particle types, and their triglyceride content was twice as high in hypertriglyceridemics compared with the other two groups. Hypertriglyceridemics had a similar concentration of total E(-)C-III(-) particles compared with normolipidemics, but the E(-)C-III(-) particles were distributed more to VLDL and IDL than to LDL. Hypercholesterolemics, in contrast, were distinguished from the normolipidemic group by 2-fold higher concentrations of apoB lipoproteins without apoE or apoC-III (E(-)C-III(-)), mainly LDL, which had high cholesterol content. Nonetheless, both normolipidemics and hypercholesterolemics had apoC-III-containing VLDL, which comprised 68% and 43% of their total VLDL particles. E(+)C-III(-) particles were a minor type, comprising <10% of particles in all lipoproteins and patient groups. Therefore, VLDL particles with apoC-III may play a central role in identifying the high risk of coronary heart disease in hypertriglyceridemia, but their substantial prevalence in normolipidemics may be of clinical significance as well.

Apolipoprotein C-III↗

VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial.

BACKGROUND: Plasma triglyceride concentration has been an inconsistent independent risk factor for coronary heart disease, perhaps because of the metabolic heterogeneity among VLDL particles, the main carriers of triglycerides in plasma. METHODS AND RESULTS: We conducted a prospective, nested case-control study in the Cholesterol and Recurrent Events (CARE) trial, a randomized placebo-controlled trial of pravastatin in 4159 patients with myocardial infarction and average LDL concentrations at baseline (115 to 174 mg/dL, mean 139 mg/dL). Baseline concentrations of VLDL-apolipoprotein (apo) B (the VLDL particle concentration), VLDL lipids, and apoCIII and apoE in VLDL+LDL and in HDL were compared in patients who had either a myocardial infarction or coronary death (cases, n=418) with those in patients who did not have a cardiovascular event (control subjects, n=370) in 5 years of follow-up. VLDL-cholesterol, VLDL-triglyceride, VLDL-apoB, apoCIII and apoE in VLDL+LDL and apoE in HDL were all interrelated, and each was a univariate predictor of subsequent coronary events. The significant independent predictors were VLDL-apoB (relative risk [RR] 3.2 for highest to lowest quintiles, P:=0.04), apoCIII in VLDL+LDL (RR 2.3, P:=0.04), and apoE in HDL (RR 1.8, P:=0.02). Plasma triglycerides, a univariate predictor of coronary events (RR 1.6, P:=0.03), was not related to coronary events (RR 1.3, P:=0.6) when apoCIII in VLDL+LDL was included in the model, whereas apoCIII remained significant. Adjustment for LDL- and HDL-cholesterol did not affect these results. CONCLUSIONS: The plasma concentrations of VLDL particles and apoCIII in VLDL and LDL are more specific measures of coronary heart disease risk than plasma triglycerides perhaps because their known metabolic properties link them more closely to atherosclerosis.

Apolipoprotein C-III↗

Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project.

BACKGROUND: Previous trials have had insufficient numbers of coronary events to address definitively the effect of lipid-modifying therapy on coronary heart disease in subgroups of patients with varying baseline characteristics. METHODS AND RESULTS: The data from 3 large randomized trials with pravastatin 40 mg were pooled and analyzed with the use of a prospectively defined protocol. Included were 19 768 patients, 102 559 person-years of follow-up, 2194 primary end points (coronary death or nonfatal myocardial infarction), and 3717 expanded end points (primary end point, CABG, or PTCA). Pravastatin significantly reduced relative risk in younger (<65 years) and older (>/=65 years) patients, men and women, smokers and nonsmokers, and patients with or without diabetes or hypertension. The relative effect was smaller, but absolute risk reduction was similar in patients with hypertension compared with those without hypertension. Relative risk reduction was significant in predefined categories of baseline lipid concentrations. Tests for interaction were not significant between relative risk reduction and baseline total cholesterol (5% to 95% range 177 to 297 mg/dL, 4.6 to 7.7 mmol/L), HDL cholesterol (27 to 58 mg/dL, 0.7 to 1.5 mmol/L), and triglyceride (74 to 302 mg/dL, 0.8 to 3.4 mmol/L) concentrations, analyzed as continuous variables. However, for LDL cholesterol, the probability values for interaction were 0.068 for the prespecified primary end point and 0.019 for the expanded end point. Relative risk reduction was similar throughout most of the baseline LDL cholesterol range (125 to 212 mg/dL, 3.2 to 5.5 mmol/L) with the possible exception of the lowest quintile of CARE/LIPID (<125 mg/dL) (relative risk reduction 5%, 95% CI 19% to -12%). CONCLUSIONS: Pravastatin treatment is effective in reducing coronary heart disease events in patients with high or low risk factor status and across a wide range of pretreatment lipid concentrations.

Aged↗

The effect of dietary patterns on blood pressure control in hypertensive patients: results from the Dietary Approaches to Stop Hypertension (DASH) trial.

To determine the impact of dietary patterns on the control of hypertension we studied the subgroup of 133 participants with systolic blood pressure (BP) of 140 to 159 mm Hg and/or diastolic BP of 90 to 95 mm Hg enrolled in the Dietary Approaches to Stop Hypertension (DASH) study. Participants were fed a control diet for a 3-week period and were then randomized to receive for 8 weeks either the control diet; a diet rich in fruits and vegetables, but otherwise similar to control; or a combination diet rich in fruits, vegetables, and low-fat dairy products, including whole grains, fish, poultry, and nuts, and reduced in fats, red meats, sweets, and sugar-containing beverages. Sodium intake and body weight were held constant throughout the study. The combination diet significantly reduced systolic BP (-11.4 mm Hg, P < .001) and diastolic BP (-5.5 mm Hg, P < .001). The fruits-and-vegetables diet also significantly reduced systolic BP (-7.2 mm Hg, P < .001) and diastolic BP (-2.8 mm Hg, P = .013). The combination diet produced significantly greater BP effects (P < .05) than the fruits-and-vegetables diet. Blood pressure changes were evident within 2 weeks of starting the intervention feeding. After the 8-week intervention period, 70% of participants eating the combination diet had a normal BP (systolic BP < 140 and diastolic BP < 90 mm Hg) compared with 45% on the fruits-and-vegetables diet and 23% on the control diet. In patients with hypertension, the DASH combination diet effectively lowers BP and may be useful in achieving control of Stage 1 hypertension.

Adult↗

Beta-carotene supplementation for patients with low baseline levels and decreased risks of total and prostate carcinoma.

BACKGROUND: The Physicians' Health Study was a randomized, double-blind, placebo-controlled trial using a 2x2 factorial design including supplementation with beta-carotene (50 mg every other day) in the primary prevention of cancer among 22,071 U.S. male physicians ages 40-84 years at randomization. Before randomization, the authors collected baseline blood specimens to determine whether any benefit was greater among or confined to those with low baseline levels of beta-carotene. METHODS: Baseline blood samples were collected from 14,916 participants. These samples were assayed, according to a nested case-control design, from 1439 men subsequently diagnosed with cancer over 12 years of follow-up (631 with prostate carcinoma) and 2204 controls matched by age and smoking habits. RESULTS: Men in the lowest quartile for plasma beta-carotene at baseline had a marginally significant (P = 0.07) increased risk of cancer compared with those in the highest quartile (relative risk [RR] = 1.30, 95% confidence interval [CI], 0.98-1.74). Men in the lowest quartile assigned at random to beta-carotene supplementation had a possible but nonsignificant decrease in overall cancer risk (RR = 0.83, 95% CI, 0.63-1.09) compared with those assigned to placebo. This was primarily due to a significant reduction in the risk of prostate carcinoma (RR = 0.68, 95% CI, 0. 46-0.99) in this group. After the first 2 years of follow-up were excluded, the results were virtually unchanged. CONCLUSIONS: These prespecified subgroup analyses appeared to support the idea that beta-carotene supplementation may reduce risk of prostate carcinoma among those with low baseline levels. Further follow-up of this population will help determine whether these findings are valid.

Adult↗

A prospective study of egg consumption and risk of cardiovascular disease in men and women.

CONTEXT: Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease (CHD). Epidemiologic studies on egg consumption and risk of CHD are sparse. OBJECTIVE: To examine the association between egg consumption and risk of CHD and stroke in men and women. DESIGN AND SETTING: Two prospective cohort studies, the Health Professionals Follow-up Study (1986-1994) and the Nurses' Health Study (1980-1994). PARTICIPANTS: A total of 37851 men aged 40 to 75 years at study outset and 80082 women aged 34 to 59 years at study outset, free of cardiovascular disease, diabetes, hypercholesterolemia, or cancer. MAIN OUTCOME MEASURES: Incident nonfatal myocardial infarction, fatal CHD, and stroke corresponding to daily egg consumption as determined by a food-frequency questionnaire. RESULTS: We documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up. After adjustment for age, smoking, and other potential CHD risk factors, we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women. The relative risks (RRs) of CHD across categories of intake were less than 1 per week (1.0), 1 per week (1.06), 2 to 4 per week (1.12), 5 to 6 per week (0.90), and > or =1 per day (1.08) (P for trend = .75) for men; and less than 1 per week (1.0), 1 per week (0.82), 2 to 4 per week (0.99), 5 to 6 per week (0.95), and > or =1 per day (0.82) (P for trend = .95) for women. In subgroup analyses, higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects (RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men, 2.02 [95% confidence interval, 1.05-3.87; P for trend = .04], and among diabetic women, 1.49 [0.88-2.52; P for trend = .008]). CONCLUSIONS: These findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women. The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research.

Adult↗