Cardiovascular diseases have been identified as "public health enemy no. 1" by the World Health Organization.
Cardiovascular diseases kill more people than any other single disease.
The search for reliable preventive methods should be pursued.
Prevention of atherosclerosis progression requires a better understanding of diet interventions.
Weekly overview on new findings and reviews.
International Society for Molecular Nutrition and Therapy
Can increased consumption of omega-3 PUFA from seafood prevent development of cardiovascular disease?
According to a number of long-standing dietary recommendations, one should increase the intake of polyunsaturated fatty acids (PUFA). While many of us became aware of the fact that compared with our ancestors, the intake of omega-6 PUFA greatly exceeds omega-3 PUFA, the impact of an increase in dietary omega-3 remained unsettled, in particular when compared with the role of alpha-linolenic acid. Many of dietary recommendations are derived from food frequency questionnaires involving difficult to resolve confounding variables. This is one of the reasons why the Multi-Ethnic Study of Atherosclerosis is of great importance. In this study of de Oliveira Otto et al. involving a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans) plasma phospholipid PUFAs were measured at baseline (2000-2002) and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease (CVD) events (including coronary heart disease and stroke) were prospectively identified through 2010. Plasma omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were inversely associated with incident CVD, with hazard ratios of 0.49 for EPA and 0.39 for DHA. Omega-3 docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race/ethnicities. It is important to note that no significant associations with CVD were observed for plasma omega-3 alpha-linolenic acid or omega-6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self-reported dietary PUFA were consistent with the PUFA biomarkers. It was concluded that the data suggest that increased consumption of omega-3 PUFA from seafood may prevent CVD development in this multiethnic population.
J Am Heart Assoc. 2013 Dec 18;2(6):e000506. doi: 10.1161/JAHA.113.000506.
Circulating and Dietary Omega-3 and Omega-6 Polyunsaturated Fatty Acids and Incidence of CVD in the Multi-Ethnic Study of Atherosclerosis.
de Oliveira Otto MC, Wu JH, Baylin A, Vaidya D, Rich SS, Tsai MY, Jacobs DR, Mozaffarian D.
Department of Epidemiology, Harvard School of Public Health, Boston, MA.
BACKGROUND: Dietary guidelines support intake of polyunsaturated fatty acids (PUFAs) in fish and vegetable oils. However, some controversy remains about
benefits of PUFAs, and most prior studies have relied on self-reported dietary assessment in relatively homogeneous populations.
METHODS AND RESULTS: In a multiethnic cohort of 2837 US adults (whites, Hispanics, African Americans, Chinese Americans), plasma phospholipid PUFAs were
measured at baseline (2000-2002) using gas chromatography and dietary PUFAs estimated using a food frequency questionnaire. Incident cardiovascular disease
(CVD) events (including coronary heart disease and stroke; n=189) were prospectively identified through 2010 during 19 778 person-years of follow-up. In
multivariable-adjusted Cox models, circulating n-3 eicosapentaenoic acid and docosahexaenoic acid were inversely associated with incident CVD, with
extreme-quartile hazard ratios (95% CIs) of 0.49 for eicosapentaenoic acid (0.30 to 0.79; Ptrend=0.01) and 0.39 for docosahexaenoic acid (0.22 to 0.67;
Ptrend<0.001). n-3 Docosapentaenoic acid (DPA) was inversely associated with CVD in whites and Chinese, but not in other race/ethnicities (P-interaction=0.01). No
significant associations with CVD were observed for circulating n-3 alpha-linolenic acid or n-6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self-reported dietary PUFA were consistent with those of the PUFA biomarkers. All associations were similar across racial-ethnic groups, except those of docosapentaenoic acid.
CONCLUSIONS: Both dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, but not alpha-linolenic acid or n-6 PUFA, were inversely associated with CVD incidence. These findings suggest that increased consumption of n-3 PUFA from seafood may prevent CVD development in a multiethnic population.
Can the Mediterranean diet be improved?
Can addition of olive oil or nuts promote atherosclerotic plaque regression?
The Mediterranean diet is a nutritional recommendation influenced by the traditional diets and lifestyle of southern Europe. Even the UNESCO recognized this diet pattern as an Intangible Cultural Heritage of Italy, Greece, Spain and Morocco including later also Portugal, Cyprus and Croatia. While observational studies and a secondary prevention trial provided evidence for an inverse relationship between cardiovascular risk and adherence to the Mediterranean diet, it remained unclear whether the diet is useful for preventing cardiovascular events. In a primary prevention trial (PREDIMED trial, Prevención con Dieta Mediterránea) involving persons at high cardiovascular risk but with no cardiovascular disease, a Mediterranean diet (MedDiet) supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. Regarding components of the primary end point (composite of acute myocardial infarction, stroke, and death from cardiovascular causes), only the comparisons of stroke risk reached statistical significance. However, no effect on all-cause mortality was apparent in the group where the MedDiet was supplemented with nuts. Can it be shown that the Mediterranean diet or components of this diet can actually interfere with progression of atherosclerosis? Sala-Vila et al. examined in a subgroup of the PREDIMED trial the effect of both supplemented MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height measured by ultrasound. After 2.4 years, ICA-IMT progressed in the control diet group while it regressed in the MedDiet+nuts group. Also maximum plaque height was reduced. It is intriguing that there were no significant changes after the MedDiet+extra virgin olive oil. Although questions remain, the study demonstrates that in addition to drugs diet interventions are useful for interfering with early progression of atherosclerosis.
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Arterioscler Thromb Vasc Biol. 2013 Nov 27. [Epub ahead of print]
Changes in Ultrasound-Assessed Carotid Intima-Media Thickness and Plaque With a Mediterranean Diet: A Substudy of the PREDIMED Trial.
Sala-Vila A, Romero-Mamani ES, Gilabert R, Núñez I, de la Torre R, Corella D, Ruiz-Gutiérrez V, López-Sabater MC, Pintó X, Rekondo J, Martínez-González MA,
Estruch R, Ros E.
From the Lipid Clinic, Endocrinology and Nutrition Service, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic,
Barcelona, Spain (A.S.-V., E.R.); Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (A.S.-V.,
E.-S.R.-M., I.N., R.d.l.T., D.C., V.R.-G., M.-C.L.-S., X.P., J.R., M.-Á.M.-G., R.E., E.R.); Department of Internal Medicine, IDIBAPS, Hospital Clinic,
Barcelona, Spain (E.-S.R.-M., R.E.); Diagnostic Imaging Centre, IDIBAPS, Hospital Clínic, Barcelona, Spain (R.G., I.N.); Human Pharmacology and Clinical
Neurosciences Research Group, Institut de Investigacions Mèdiques Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University
of Valencia, Valencia, Spain (D.C.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Sevilla, Spain (V.R.-G.); Department of Nutrition
and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (M.-C.L.-S.); Lipids and Vascular Risk Unit, Internal Medicine,
Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain (X.P.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain
(J.R.); and Department of Preventive Medicine and Public Health, School of Medicine, University of Navarra-Clínica Universidad de Navarra, Pamplona, Spain
(M.-Á.M.-G.).
OBJECTIVE: The Prevención con Dieta Mediterránea (PREDIMED) trial showed that a Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil or
30 g/d of mixed nuts reduced incident cardiovascular events compared with a control (low fat) diet. The mechanisms of cardiovascular protection afforded by
MedDiets remain to be uncovered. We assessed the effect of both supplemented MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height,
the ultrasound features that best predict future cardiovascular events, in subjects at high cardiovascular risk.
APPROACH AND RESULTS: In a PREDIMED subcohort (n=175), plaque height and carotid IMT of 3 prespecified segments (ICA, bifurcation, and common) were
sonographically assessed at baseline and after intervention for a mean of 2.4 years. We evaluated 164 subjects with complete data. In a multivariate model,
mean ICA-IMT progressed in the control diet group (mean [95% confidence interval], 0.052 mm [-0.014 to 0.118 mm]), whereas it regressed in the
MedDiet+nuts group (-0.084 mm [-0.158 to -0.010 mm]; P=0.024 versus control). Similar results were observed for maximum ICA-IMT (control, 0.188 mm [0.077 to
0.299 mm]; MedDiet+nuts, -0.030 mm [-0.153 to 0.093 mm]; P=0.034) and maximum plaque height (control, 0.106 mm [0.001 to 0.210 mm]; MedDiet+nuts, -0.091 mm
[-0.206 to 0.023 mm]; P=0.047). There were no changes in ICA-IMT or plaque after the MedDiet+extra virgin olive oil.
CONCLUSIONS: Compared with a control diet, consumption of a MedDiet supplemented with nuts is associated with delayed progression of ICA-IMT and plaque. The
results contribute mechanistic evidence for the reduction of cardiovascular events observed in the PREDIMED trial.
Do daily three tablespoons of milled flaxseed reduce blood pressure in hypertensive patients?
High blood pressure and in particular isolated systolic hypertension is a major factor contributing to endothelial damage and thus development of atherosclerotic plaques. In clinical practice, reducing blood pressure to recommended values is often difficult to achieve even with triple antihypertensive therapy. One of the new approaches to interfere with resistant hypertension is renal denervation which targets sympathetic hyperactivity. It is in this context an important finding by Rodriguez-Leyva et al. that daily consumption of flaxseed reduced blood pressure in hypertensive patients: In this pioneering prospective randomized trial, patients consumed a variety of foods which contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the omega-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed group. Systolic blood pressure was ≈10 mm Hg lower, and diastolic blood pressure was ≈7 mm Hg lower in the flaxseed group. Patients with systolic blood pressure ≥140 mm Hg exhibited a reduction of 15 mm Hg in systolic blood pressure and 7 mm Hg in diastolic blood pressure. Blood alpha-linolenic acid correlated with changes in systolic blood pressure, and lignan levels with changes in diastolic blood pressure. Rodriguez-Leyva et al. concluded that flaxseed induced one of the most potent antihypertensive effects achieved by a dietary intervention. As regards mechanisms involved in the blood pressure lowering, an increase in prostacyclin production observed previously by Rupp et al. in spontaneously hypertensive rats fed increasing amounts of an alpha-linolenic acid rich diet could be involved. In this experiment, blood pressure lowering (radiotelemetric monitoring) was more pronounced in the sleeping period.
Hypertension. 2013 Dec;62(6):1081-9. doi: 10.1161/HYPERTENSIONAHA.113.02094. Epub 2013 Oct 14.
Potent antihypertensive action of dietary flaxseed in hypertensive patients.
Rodriguez-Leyva D, Weighell W, Edel AL, Lavallee R, Dibrov E, Pinneker R, Maddaford TG, Ramjiawan B, Aliani M, Guzman R, Pierce GN.
St Boniface Hospital Research Centre, 351 Tache Ave, Winnipeg, Manitoba, Canada R2H 2A6. gpierce@sbrc.ca.
Flaxseed contains ω-3 fatty acids, lignans, and fiber that together may provide benefits to patients with cardiovascular disease. Animal work identified that
patients with peripheral artery disease may particularly benefit from dietary supplementation with flaxseed. Hypertension is commonly associated with
peripheral artery disease. The purpose of the study was to examine the effects of daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP)
in peripheral artery disease patients. In this prospective, double-blinded, placebo-controlled, randomized trial, patients (110 in total) ingested a variety
of foods that contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans
increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group. Patient body weights were not significantly
different between the 2 groups at any time. SBP was ≈10 mm Hg lower, and DBP was ≈7 mm Hg lower in the flaxseed group compared with placebo after 6 months.
Patients who entered the trial with a SBP ≥140 mm Hg at baseline obtained a significant reduction of 15 mm Hg in SBP and 7 mm Hg in DBP from flaxseed
ingestion. The antihypertensive effect was achieved selectively in hypertensive patients. Circulating α-linolenic acid levels correlated with SBP and DBP, and
lignan levels correlated with changes in DBP. In summary, flaxseed induced one of the most potent antihypertensive effects achieved by a dietary intervention.
Can dietary flaxseed promote atherosclerotic plaque regression in an animal experiment?
Although it has been shown that flaxseed can retard the progression of atherosclerotic plaques, it remained unresolved whether regression of established atherosclerotic plaques can be accelerated by dietary flaxseed. It was, therefore, important to examine whether in rabbits fed a 1% cholesterol-supplemented diet, plaque regression can be accelerated by feeding a 10% flaxseed diet. In the study of Francis et al., rabbits were assigned to receive either a regular diet for 12 wk (group I) or a 1% cholesterol-supplemented diet for 4 wk followed by a regular diet for 8 wk (group II). The remaining animals were treated as in group II but were fed for an additional 14 wk with either a regular diet (group III) or a 10% flaxseed-supplemented diet (group IV). Animals in group II showed clear evidence of plaque growth stabilization. Dietary flaxseed resulted in a significant ≈40% reduction in plaque formation. Animals in groups II and III exhibited improved contraction and endothelium-dependent vessel relaxation. Francis et al. concluded that dietary flaxseed represents a valuable strategy to accelerate the regression of atherosclerotic plaques.
Am J Physiol Heart Circ Physiol. 2013 Jun 15;304(12):H1743-51. doi: 10.1152/ajpheart.00606.2012. Epub 2013 Apr 12.
Effects of dietary flaxseed on atherosclerotic plaque regression.
Francis AA, Deniset JF, Austria JA, LaValleé RK, Maddaford GG, Hedley TE, Dibrov E, Pierce GN.
Canadian Centre for Agri-food Research in Health and Medicine and the Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre, Department of
Physiology, Faculties of Medicine and Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.
21.12.2013 (HR)