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From the Townsend Letter
May 2013

reviewed by Jule Klotter
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Diet Treatment for Cardiovascular Disease
A diet rich in vegetables, fruits, and nuts significantly reduces the risk of cardiovascular events and CV-related deaths in at-risk patients, according to two large, new studies. A 2012 prospective cohort study, led by Mahshid Dehghan, PhD, looked at diet quality and risk of cardiovascular events in 31,546 volunteers with CV disease or diabetes (aged 55 or older) enrolled in two large drug studies: ONTARGET and TRANSCEND. Both were parallel, multinational, double-blind, randomized trials, involving people from 40 middle- and high-income countries. ONTARGET evaluated the effects of telmisartan (angiotensin II receptor antagonist), ramipril (angiotensin-converting enzyme/ACE inhibitor), or their combination. TRANSCEND compared telmisartan with placebo. Participants were followed for a median of 56 months in both studies.

Dehghan and colleagues used a qualitative food frequency questionnaire, previously used in the INTERHEART study, to assess diet quality and then created a healthful eating index and diet risk score. The INTERHEART study pinpointed fruits, green leafy vegetables, and other vegetables (raw and cooked) as beneficial for lowering heart attack risk. Meat, fried foods, and "salty snacks" were associated with increased heart attack risk. Dehghan and colleagues divided patients' diet risk scores into quintiles; patients who ate mostly beneficial foods (fruits, vegetables, nuts, and fish) were in the highest quintile. The researchers found a significant reduced risk, in the top quintile compared with the bottom quintile, of death from cardiovascular disease (35%), reduced risk of myocardial infarction (14%), and reduced risk of stroke (19%) – "regardless of whether patients were receiving proven drugs."

"Highlighting the importance of healthy eating by health professionals and advising high-risk individuals to improve their diet quality would substantially reduce CVD recurrence beyond drug therapy alone and save lives globally," state the authors.

A 2013 controlled, randomized study, the PREDIMED trial, compared the effect of two variations of a Mediterranean-type diet with a control group who received advice on a healthful, low-fat diet. The study followed 7447 men and women over age 50 with diabetes or at least three risk factors for cardiovascular disease for a median of 4.8 years (October 2003–June 2009). Because this study was held in Spain, the control group's regular diet contained more fruits and vegetables than found in a typical American diet. However, participants in the study's Mediterranean-diet groups ate more fish and legumes than meat than did the controls. In addition, one Mediterranean-type group were given mixed nuts (walnuts, almonds, and hazelnuts) as part of their diet, and the other group were told to increase their consumption of extra-virgin olive oil. The researchers found little difference in the outcomes of the two Mediterranean-diet groups. Both groups had " … an absolute risk reduction of approximately 3 major cardiovascular events [myocardial infarction, stroke, and CV-related death] per 1000 person-years, for a relative risk reduction of approximately 30% among high-risk persons who were initially free of cardiovascular disease," compared with controls. The authors credited the supplemental fats in the olive oil and nuts for the risk reduction.

Dehghan M, Mente A, Teo KK, et al. Relationship between healthy diet and risk of cardiovascular disease among patients on drug therapies for secondary prevention: a prospective cohort study of 31 546 high-risk individuals from 40 countries. Circulation. 2012;126:2705–2712. Available at Accessed February 16, 2013.

Estruch R, Ras E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. Epub February 25, 2013 Available at Accessed February 25, 2013.

Fluoride and Arterial Calcification
Does fluoride contribute to coronary artery calcification? Studies over the past six decades have reported a connection between fluoride, calcium accumulation, and the aorta, according to Tara Blank, PhD. A limited number of human studies have reported coronary artery calcification and loss of arterial elasticity in people with endemic fluorosis. Elasticity loss and calcification are considered major predictors of cardiovascular events. In a 2010 study, fluorosis patients had significantly higher aortic strain index, indicating less elasticity in the ascending aorta, than controls (3.4 ± 0.6 vs. 3.0 ± 0.4; p < 0.001, respectively). A 2013 study found that heart recovery rate index abnormalities were significantly higher in fluorosis patients compared with controls. Heart recovery rate index is a marker of autonomic nervous system function.

In a 2011 study, Yuxin Li and colleagues observed a relationship between fluoride uptake and vascular calcification in coronary arteries. They reviewed sodium 18F-fluoride PET/CT imaging data and cardiovascular history belonging to 61 patients who had received full-body scans at Veterans Affairs Greater Los Angeles Healthcare System in 2009–2010. Although sodium 18F-fluoride PET/CT is primarily used to locate ongoing bone formation, this technology can also identify atherosclerotic calcification, according to research by T. Derlin and colleagues (J Nucl Med. 2011;52:362–368). Derlin et al. found mineral deposits in carotid plaque that "significantly [correlated] with atherogenic risk factors," according to Li et al.

In reviewing patients' imaging data, Li and colleagues located 361 sites of fluoride uptake in major artery walls in 59 (97%) patients and 317 calcification sites in 49 (88%) patients. "Fluoride uptake either overlaps with calcification or locates adjacent to the detectable calcium deposits," the authors state, "suggesting that fluoride uptake and detectable calcification represent different stages of the atherosclerotic process." They found no significant correlation between the presence of coronary fluoride uptake and cardiovascular risk factors, possibly due to the small number of people involved. Only 42 of the 61 patients had more than one cardiovascular risk factor (hypertension, obesity, diabetes, high cholesterol, smoking history, coronary artery disease history). However, patients who had experienced one or more cardiovascular events had significantly higher coronary fluoride uptake than patients without a history of CV events. This study presents two avenues for further research: the use of fluoride PET/CT imaging as a means of diagnosing atherosclerosis and increased fluoride uptake as a possible predictor of cardiovascular disease.

Adali MK, Varol E, Aksoy F, et al. Impaired heart rate recovery in patients with endemic fluorosis [abstract]. Biol Trace Elem Res. February 2013.Available at Accessed March 13, 2013.

Blank T. Fluoride & arterial calcification. July 2012. Available at Accessed February 22, 2013.

Li Y, Berenji GR, Shaba WF, Tafti B, Yevdayev E, Dadparvar S. Association of vascular fluoride uptake with vascular calcification and coronary artery disease. Nucl Med Commun. 2011. Available at Accessed February 25, 2013.

Varol E, Akcay S, Ersoy IH, Ozaydin M, Koroglu BK, Varol S. aortic elasticity is impaired in patients with endemic fluorosis [abstract]. Biol Trace Elem Res. February 2010; 133(2):121–127. Available at Accessed February 25, 2013.

Positive Psychology and Acute Cardiovascular Disease
A group of Boston researchers recently developed and tested a positive psychology intervention on patients who were hospitalized with acute coronary syndrome or congestive heart failure. Positive psychology focuses on the cultivation of positive emotions, such as happiness, optimism, gratitude, and kindness. Positive emotions reduce inflammation and benefit the autonomic nervous system. Heart patients who exhibit positive emotional states have fewer readmissions, increased survival after cardiac surgery, and lower death rates. This positive psychology study, led by Jeff C. Huffman, is among the first to test the possibility of implementing a clinical intervention designed to increase positive emotions in cardiac patients.

The Boston research team developed an 8-week intervention based on The How of Happiness by Dr. Sonja Lyubomirsky (Department of Psychology, University of California-Riverside). Each week, cardiac patients were given an exercise (to be completed in one day) designed to cultivate optimism, gratitude, or kindness. Most of these exercises had produced sustained well-being, increased happiness, and/or better health in randomized clinical trials. A social worker on the cardiac unit introduced the program and its rationale to patients before their discharge from the hospital and maintained contact with 15-minute weekly phone calls. "The role of the trainer was not to perform an interpersonal therapeutic intervention," the authors explain, "but rather to describe and review exercises performed independently by participants. Thus, the trainer's responsibilities were straightforward and easily learned." The research team designed the intervention for use in clinical settings.

Huffman and colleagues used a small three-arm study to test the intervention's feasibility. Twenty-three patients were randomized into three groups: Positive Psychology (PP), Relaxation Response (RR), and Recollection. In addition to the in-hospital introduction described above, PP patients (n = 9) received a manual that explained each week's activity as well as a copy of Lyubomirsky's book. RR patients (n = 7), acting as an active control, were taught a 20-minute relaxation exercise with previously validated benefits for cardiac patients. Patients were asked to perform the relaxation exercise daily. The Recollection group (n = 7), the attentional control, was asked to recall and list events from the previous week. Unlike the PP exercises, this activity did not ask patients to focus on emotional states. All three groups received weekly phone calls from the social worker.

To assess feasibility, the researchers looked at completion rates, asked for patient feedback, and used five different psychological tests to measure changes in patients' depression, anxiety, happiness, and quality of life. The positive psychology group had the highest trial completion rate (76.5%), followed by the recollection group (70.9%) and the relaxation response group (64.0%). Patients remaining in the RR group at study's end were "slightly more likely" than the positive psychology participants to say they would continue to use their intervention. PP received higher easy-to-complete and globally useful scores than the other two interventions. Optimism score improvement from baseline measures was highest in the PP patients (4.00) and least in the recollection group (2.71). The PP group also showed the greatest improvement in depression, anxiety, and health-related quality of life scores. Both the PP and RR groups showed improved happiness; RR patients had the greatest improvement according to the Subjective Happiness Scale, and PP patients had the greatest improvement according to the CES-D subscale.

This small feasibility study is just the beginning. "Additional refinement and testing of this positive psychology intervention for cardiac patients are required to ensure that the field can develop the best intervention to impact meaningful clinical outcomes," say the authors.

Huffman JC, Mastromauro CA, Boehm JK, et al. Development of a positive psychology intervention for patients with acute cardiovascular disease. Heart International 2011;6:e13. Available at Accessed February 25, 2013.

Polyunsaturated Fats and Cardiovascular Disease
For decades, the primary characteristic of a healthy-heart diet has been the use of polyunsaturated vegetable oils in place of saturated fats, found in meat, eggs, and dairy products. A revisit to the decades-old Sydney Diet Heart Study and an updated meta-analysis has challenged this advice and the assumption that lower cholesterol levels decrease cardiovascular mortality. The original Sydney Diet Heart Study (SDHS), published in 1978, used overall mortality alone as the primary outcome. Christopher E. Ramsden and colleagues were able to acquire unpublished data regarding cardiovascular and coronary mortality from SDHS researcher B. Leelarthaepin and conduct their own statistical analysis. Theythen updated their 2010 meta-analysis of polyunsaturated fatty acid intervention trials and risk of cardiovascular disease and coronary heart disease mortality (Br J Nutr. 2010;104:1586–1600).

The Sydney Diet Heart Study, conducted in 1966–1973, involved 458 Australian men, aged 30 through 59, who had had a recent coronary event. The men were randomly assigned to a control group that received no specific dietary advice and an intervention group that received safflower oil and safflower oil margarine, which was made up almost entirely of linoleic acid (an omega-6 polyunsaturated fatty acid). The intervention group were told to increase their consumption of safflower oil and decrease saturated fat consumption. The safflower oil margarine was known to decrease cholesterol levels, and the original research team documented greater total cholesterol reduction in the intervention group than in the controls (−13.3% vs. −5.5%; p < 0.001). SHDS data revealed no significant difference in triglycerides, body mass index, or systolic or diastolic blood pressure at baseline or during follow-up between the two groups.

Statistical analysis conducted by Ramsden et al. showed that the safflower oil group "had an increased risk of all cause mortality (17.6% v 11.8%; hazard ratio 1.62 (95% confidence interval 1.00 to 2.64); P = 0.051), cardiovascular mortality (17.2% v 11.0%; 1.70 (1.03 to 2.80); P=0.037), and mortality from coronary heart disease (16.3% v 10.1%; 1.74 )1.04 to 2.92); P=0.036)." Ramsden and colleagues say that these SDHS outcomes correspond to results from two randomized controlled trials that used corn oil (also high in omega-6 PUFAs) instead of safflower oil. Unlike the omega-6-dominated safflower oil and corn oil studies, studies that included omega-3 PUFAs (i.e., eicosapentaenoic acid, docosahexaenoic acid, and a-linolenic acid) found a beneficial effect on cardiovascular outcomes: " … pooled analysis of the four randomized controlled trials that increased n-3 PUFAs alongside n-6 LA showed reduced cardiovascular mortality (0.79 (0.63 to 0.99); P=0.04)."

A BMJ online commentary about the Ramsden study states: "UK dietary recommendations are cautious about high intakes of omega 6 PUFAs, but some other health authorities, including the American Heart Association, have recently repeated advice to maintain, and even to increase, intake of omega 6 PUFAs. This has caused some controversy because evidence that linoleic acid lowers the risk of cardiovascular disease is limited." ("Limited" seems to be an understatement.)

Ramsden CE, Zamora D, Leelarthaepin B, et al. Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. BMJ. February 5, 2013:346:e8707. Available at Accessed February 25, 2013.

Study raises questions about dietary fats and heart disease guidance [online article]. BMJ. February 5, 2013. Accessed February 25, 2013.
(Editor note: Access via

Mild Hypertension Treatment
Antihypertensive treatment showed little benefit for people with mild hypertension and no previous cardiovascular event, according to a 2012 Cochrane meta-analysis of four studies. "Individuals with mildly elevated blood pressures, but no previous cardiovascular events, make up the majority of those considered for and receiving antihypertensive therapy," say the Cochrane reviewers. "The decision to treat this population has important consequences for both the patients (e.g. adverse drug effects, lifetime of drug therapy, cost of treatment, etc.) and any third party payer (e.g. high cost of drugs, physician services, laboratory tests, etc.)." Mild hypertension (a.k.a. stage 1) is defined as a systolic blood pressure (BP) of 140 to 159 mm Hg and/or a diastolic BP of 90 to 99 mm Hg. Thiazide-type diuretics are recommended for mild hypertension, according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7). For high-risk patients, such as those with chronic kidney disease or diabetes, a combination of drugs (i.e., angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, and calcium channel blockers) is used in the hope of bringing BP levels down to 130/80 mm Hg or less.

The Cochrane research team, led by Diana Diao of the University of British Columbia (Vancouver, Canada), searched CENTRAL (2011, Issue 1), MEDLINE (1948 to May 2011), EMBASE (1980 to May 2011), and article reference lists for randomized controlled trials of antihypertensive drug treatment. They found four trials with a total of 8912 participants "that either provided individual patient data – to allow for the selection of patients with mild hypertension only – or had a patient population that was at least 80% mild hypertension," according to MedPage Today.

When compared with placebo, 4 to 5 years of treatment did not reduce coronary heart disease (RR 1.12, 95% 0.80, 1.57) or cardiovascular events (RR 0.97, 95% CI 0.72, 1.32) in people with mild hypertension and no previous cardiovascular event. The Cochrane reviewers found a nonsignificant reduction in overall mortality risk (RR 0.85, 95% CI 0.63, 1.15) and stroke (RR 0.51, 95% CI 0.24, 1.08). Only one of the four trials contained data on patient withdrawals due to drugs' adverse effects. That study found an absolute risk increase of 8.9%. "More RCTs are needed in this prevalent population to know whether the benefits of treatment exceed the harms," the reviewers conclude.

Lifestyle modification is indicated for all people with hypertension, according to JNC7, and encouraged in people with normal blood pressure. Maintaining a normal body weight, reducing dietary sodium, following the DASH diet, physical activity, and limiting alcohol consumption have been shown to reduce systolic pressure. Systolic pressure fell 5 to 20 mm Hg for every 10 kg (about 4.5 pounds) of weight loss in clinical studies, and "a 160 mg sodium DASH eating plan has effects similar to single drug therapy," according to JNC7. It is not unreasonable to use lifestyle changes to reduce mild hypertension before turning to pharmaceuticals.

Diao D, Wright JM, Cundiff DK, Gueyffier F. Benefits of antihypertensive drugs for mild hypertension are unclear [online article summary]. November 14, 2012. Accessed February 22, 2013.

National Institutes of Health. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. December 2002. Available at Accessed February 25, 2013.

Neale T. Benefits iffy for drugs in mild hypertension [online article]. MedPage Today. August 16, 2012. Accessed March 13, 2013.

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Jule Klotter

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