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There is now mounting evidence that erectile dysfunction (ED) is an early predictor of coronary heart disease (CHD). Men presenting with ED but no other cardiovascular symptoms provide an opportunity for the treating physician to test for asymptomatic CHD and to reduce CHD risk factors.

Soy protein-containing foods are a rich source of isoflavone phytoestrogens, such as genistein and daidzein. There is great interest in these substances, as lower rates of chronic diseases, including coronary heart disease, have been associated with high dietary intake of soy-containing foods. Soy phytoestrogens bind weakly to estrogen receptors, and some bind more strongly to estrogen receptor-beta compared with estrogen receptor-alpha. A meta-analysis has indicated that isoflavone phytoestrogens lowered plasma cholesterol concentrations in subjects with initially elevated levels, but had little effect in subjects with normal cholesterol concentrations. These substances reportedly may also have beneficial effects on arterial endothelial function. In addition to these potentially antiatherogenic effects, many laboratories are investigating other possible mechanisms, including antioxidative and antiproliferative properties of these substances. We have shown that dietary supplementation with soy-derived isoflavones reduced the in vitro oxidation susceptibility of low-density lipoprotein (LDL). To further explore this phenomenon, we incorporated genistein and daidzein into LDL molecules in vitro with the aid of an artificial transfer system. However, it was necessary to convert the isoflavone molecules to fat-soluble derivatives, fatty acid esters (analogous to esterified endogenous estrogens, which are known to occur in vivo), to achieve significant incorporation. The LDLs containing esterified isoflavones were shown to be less susceptible to oxidation in vitro than native LDL. We also employed U937 cell cultures for investigating the effects of isoflavone-containing LDLs on cell proliferation. Some of these LDLs exhibited antiproliferative effects in cultured U937 cells. In summary, lipophilic phytoestrogen derivatives could be incorporated into LDLs, increasing their oxidation resistance and antiproliferative efficacy ex vivo, both of which are, in theory, antiatherogenic effects. Further studies are needed to assess to what extent analogous effects could be produced in vivo and whether such substances have a role in hormone replacement and coronary heart disease prevention in postmenopausal women.

The results from a survey in Finland suggest an important treatment gap of lipid-lowering medications. Patients whose coronary artery disease was diagnosed before 1995 were less likely to be on lipid therapy than patients with a more recent diagnosis.

Objectives: To review some aspects in the recent literature related to the effects of postmenopausal estrogen and progestin use on major plasma lipoprotein risk factors for coronary heart disease (CHD)., Methods: Collection of relevant information from medical journals, and by the use of Medline and Current Contents., Results: The beneficial effects of estrogen (LDL cholesterol reduction and HDL cholesterol elevation) are well established. The effects on HDL are modified to different degrees by progestins, depending on the androgenic properties of the latter: the 'sex steroid sensitive' HDL2 subfraction is decreased by nortestosterone derived progestins with androgenic activity. Recently developed methodology employing stable isotopes has helped to clarify underlying mechanisms. Progestins alone, as well as estrogen-progestin combinations have been shown to reduce the plasma levels of Lp(a), another lipoprotein risk factor for CHD. According to one study, estrogen administered alone had a similar effect., Conclusions: The effects of hormone replacement therapies on lipid metabolism have been partly established and investigations on the underlying mechanisms are being published. This information will be useful for developing new replacement regimens with more protection against CHD and less adverse effects.

A wide consensus has been reached concerning the importance of lipid-lowering drug therapy in patients with dyslipidaemia with overt coronary heart disease. This consensus is also likely to be reflected in the more active treatment of other high-risk patient groups. The statin family of drugs has been tested in a large secondary prevention study, the Scandinavian Simvastatin Survival Study, and in angiographic trials. Their role in the treatment of hypercholesterolaemia and mixed hyperlipidaemia is increasing, whereas fibrates are increasingly limited to hypertriglyceridaemia.

Heart rate (HR) variability is impaired in chronic coronary artery disease (CAD), but the mechanism is not fully resolved. This study was aimed at assessing whether HR variability is influenced by the risk factors of CAD. Of a random sample of 120 subjects born in 1954, 88 (41 men and 47 women) could be included in the analyses. No subject had clinical heart disease. The subjects' physical activity, alcohol consumption and smoking were quantified by 2-month diary follow-up. Serum lipids and insulin were measured. The tests of HR variability included power spectral analysis and calculation of the root-mean-square difference of RR intervals at rest under controlled respiration. HR variability indexes were asymmetrically distributed and strongly HR-dependent, and therefore, all statistical tests were performed on log-transformed data adjusted to the population mean HR. Multiple regression analyses showed independent inverse relations between the root-mean-square RR difference and low-density lipoprotein (LDL) cholesterol (beta = -0.22; p = 0.008), and between the total RR-interval power and LDL cholesterol (beta = -0.25; p = 0.007), as well as smoking (beta = -0.19; p = 0.035). In women, alcohol use influenced the RR-interval root-mean-square difference (beta = 0.31; p = 0.015), total power (beta = 0.33; p = 0.017) and high-frequency power (beta = 0.26; p = 0.056). It is concluded that short-term HR variability is related inversely to LDL cholesterol and smoking in the population, and directly to alcohol use in women.(ABSTRACT TRUNCATED AT 250 WORDS)

The genetic variation of apolipoprotein B has been studied extensively in Finns with the aid of protein and DNA polymorphisms. Population association studies confirmed significant associations between the XbaI polymorphism of the apolipoprotein B gene and elevated serum cholesterol levels, and dietary studies suggested that the XbaI and ins/del polymorphisms might modify the serum lipid response to dietary fat intake. Studies comparing patients and controls, however, did not confirm previous studies suggesting that the multi-allelic variation at the 3'VNTR region of the apolipoprotein B gene was associated with coronary artery disease. The results suggest that the apolipoprotein B gene is involved in the regulation of serum lipid levels. A yet unknown mutation in linkage disequilibrium with the XbaI site may contribute to this regulation.

Previous studies have suggested that some apolipoprotein B (apoB) 3' variable number of tandem repeats (3'VNTR) locus alleles are associated with coronary artery disease (CAD). We examined the possible association between the apoB 3'VNTR alleles and CAD in 387 Finnish subjects. Using the polymerase chain reaction and polyacrylamide gel electrophoresis, the 3'VNTR genotype was determined in 187 individuals with severe CAD confirmed by coronary angiography (patients), in 121 individuals with normal coronary angiograms (controls), and in 79 apparently healthy subjects (normals). In contrast to previous reports from other populations, the larger apoB 3'VNTR alleles were not significantly more frequent among CAD patients than among controls or normals. In addition, there was no significant association between the 3'VNTR alleles and serum lipid levels in this Finnish population.

Fresh blood samples were collected from 103 North Karelians who had in 1981-84 participated in dietary intervention studies and analysis of the XbaI restriction fragment length polymorphism (RFLP) of apolipoprotein B (apoB) was carried out. Reanalysis of the original plasma lipid and apolipoprotein data indicated that while baseline concentrations did not differ significantly between genotypes, the response to a low-fat, low-cholesterol diet was influenced by apoB XbaI genotype: reductions in total and low density lipoprotein (LDL) cholesterol, apoB and high density lipoprotein (HDL) cholesterol were greater in subjects homo- or heterozygous for the presence of the XbaI cutting site (X1X2 or X2X2 genotype, designated X2+) as compared to those lacking the cutting site (X1X1 genotype, designated X2-). The corresponding average reductions induced by dietary intervention in X2+ and X2- subjects were: for total cholesterol 1.30 and 0.99 mmol/l (p = 0.036), for LDL cholesterol 1.04 and 0.78 mmol/l (p = 0.049), for apoB 18.3 and 8.1 mg/100 ml (p = 0.012) and for HDL cholesterol 0.26 and 0.17 mmol/l (p = 0.008).

The 'cholesterol hypothesis' has been proven in a wealth of experimental, clinical, genetic and epidemiological studies. Cholesterol-lowering trials reviewed here have compared the effects of various treatment modalities on coronary heart disease reduction. They have shown that prevention of coronary heart disease depends on the magnitude and duration of cholesterol reduction, not on the way it was achieved. Collective evidence from all unconfounded trials indicates that most of the benefit of such intervention is achieved within relatively few years of starting the intervention. With the possible exception of adverse effects associated with clofibrate, cholesterol-lowering intervention has not produced any untoward effects that cause concern.