Shorts

briefed by Jule Klotter

Screening for Cardiovascular Disease

The widely used Framingham risk score is no more accurate in predicting the odds of a cardiovascular event than age alone, according to a 2011 PLoS ONE article. The Framingham risk score is based on age, gender, cholesterol, smoking status, systolic blood pressure, and whether a person is taking blood pressure medication. The score indicates the odds of having a cardiovascular event within the next 10 years. Treatment is recommended when the calculated risk is 20% or more. The risk score’s role in preventing cardiovascular morbidity and mortality has never “been tested in a rigorous way,” says Michael S. Lauer, MD, at the National Heart, Lung, Blood Institute (Bethesda, Maryland).

Nicholas J. Wald, Mark Simmonds, and Joan K. Morris used statistical modeling, based on observed data, to compare age screening and the Framingham risk score. The three British researchers identified age 55 as the point at which people have a 20% risk of a cardiovascular event within the next 10 years. Age screening would catch 86% of cardiovascular events with a 24% false-positive rate, according to their analysis. The Framingham risk score, with its 20% risk cut-off, also gives an 86% detection rate but with a false-positive of 21%. Age screening, the researchers argue, would save time and health care dollars. Repeated blood tests to assess cholesterol levels and multiple doctor visits to discuss risk assessment would no longer be necessary.

“One implication of the new study is that everybody might begin treatment at 55,” Richard Smith, Director of UnitedHealth Chronic Disease Initiative, wrote in his commentary on the PLoS ONE study. “This fits with the strategy proposed by Wald and Law in 2000 and in 2003 in the BMJ to take a polypill containing blood pressure lowering drugs, a statin, and possibly aspirin and folic acid.” Research studies show that polypills can reduce blood pressure and serum cholesterol, but it will take years to assess their ability to reduce cardiovascular events and mortality rates. Long-term tests that track the medication’s effect on actual disease and mortality, and its adverse effects have not yet been performed.

Instead of using risk factors to screen for cardiovascular disease, some are advocating the routine use of imaging technology, says Dr. Michael S. Laurer. Laurer, however, is concerned that imaging screening will lead to overdiagnosis. He says, “Many, often most, people with abnormal screening test findings will nonetheless remain free of clinical disease; for example, among adults with high coronary calcium scores in the MESA (Multi-Ethnic Study of Atherosclerosis), 95% remained asymptomatic over the next 5 years.” A positive screen often propels worried practitioners and patients to commence a series of “potentially risky” tests and treatments. He calls for “definitive large-scale randomized trials” to determine the most accurate means of assessing cardiovascular disease risk.

Lauer MS. Screening asymptomatic subjects for subclinical atherosclerosis. J Am Coll Cardiol. 2010;56(2). Available at http://content.onlinejacc.org/article.aspx?articleid=1142958&issueno=2. Accessed February 20, 2013.

Smith R. Screening for cardiovascular disease using age alone: reflections on a paper peer-reviewed as both ‘radical’ and ‘unsurprising.’ J Med Screen. 2011;18:113–114. Available at http://171.66.127.126/content/18/3/113.full.pdf&html. Accessed February 20, 2013.

Wald NJ, Simmonds M, Morris JK. Screening for future cardiovascular disease using age alone compared with multiple risk factors and age. PLoS ONE. May 2011;6(5): e18742. Available at www.plosone.org/article/info:doi/10.1371/journal.pone.0018742. Accessed February 20, 2013.

C-Reactive Protein and Cardiovascular Disease

When FDA approved the statin Crestor in 2010, for use in men over 50 and women over 60 with normal cholesterol levels but high C-reactive protein (<2.0 mg/dL) and one additional cardiovascular risk factor, the agency was acknowledging inflammation’s role in cardiovascular disease. C-reactive protein (CRP) appears in serum when inflammation or necrosis is present and “disappears when an inflammatory process is suppressed by salicylates, steroids, or both” (Mosby’s). Although C-reactive protein is an accurate biomarker for inflammation, two recent studies cast doubt on its usefulness in predicting cardiovascular disease.

As part of the Dallas Heart Study, Nitin K. Gupta and colleagues decided to investigate the relationship of CRP, cardiovascular disease, and body mass index (BMI). The body produces CRP in response to interleukin (IL)-6, a cytokine produced by leukocytes and smooth muscle cells in atherosclerotic plaques; but atherosclerotic plaque is not the only source of IL-6. Adipose tissue (body fat) also produces IL-6. The researchers point out that most studies showing a correlation between CRP and cardiovascular disease have involved subjects “who are less obese than the current U.S. population, where now more than two-thirds of adults are overweight or obese.”

The Dallas Heart Study involves a multiethnic, population-based probability sample of 6101 Dallas County adults, aged 30 to 65 years, who completed a detailed in-home survey. For this investigation of CRP and BMI, Gupta and colleagues used data from 2899 of the subjects who had also provided blood and urine samples and undergone various imaging procedures. The researchers looked for associations between CRP levels, coronary artery calcium (n = 2685), aortic wall thickness (n = 2238), and aortic plaque burden (n = 2224) according to BMI categories (normal, 18.5 to <25 kg/m²; overweight, 25 to <30 kg/m²; obese, ≥30 kg/m²). In this study, 38% of men and 53% of women were obese.

As BMI increased, the correlation between C-reactive protein levels and cardiovascular imaging evaluations decreased. “Increasing CRP levels (<1 mg/l, 1 to 3 mg/l, >3 mg/l) were associated with increased [coronary artery calcium] prevalence in normal and overweight men and in normal weight women (p < 0.01), but not in obese subjects of either sex,” say the authors. “Likewise, the correlations between CRP and [aortic wall thickness] and [aortic plaque burden] diminished with increasing BMI and were nonsignificant in obese individuals (p < 0.05 in nonobese, p > 0.1 in obese.”

A 2013 study, led by J. S. Ho, investigates the ability of C-reactive protein and coronary artery calcium (CAC) to predict the presence of obstructive coronary artery stenoses. This Texas study involved 1079 people whose traditional cardiovascular risk screening put them at low risk for cardiovascular disease. Coronary computed tomographic angiography found 38 severely obstructive stenoses in the population (3.5%), which were confirmed with invasive coronary angiography. Angina (p < 0.001), an elevated coronary arterial calcium score (p < 0.001), and the use of antihypertensive agents (p = 0.03) were the best predictors of severely obstructed blood flow in coronary arteries. The researchers saw a direct correlation between a rise in coronary artery calcium scores and the frequency of obstructive stenosis. Not all people with high scores had stenosis, but stenosis was uncommon when coronary arterial calcium was not detected. The researchers saw no significant correlation between CRP and stenosis.

The idea of using high-sensitivity C-reactive protein measures to predict cardiovascular disease appears to need rethinking.

C-reactive protein (CRP). Mosby’s Medical Dictionary. 6th ed. St. Louis: Mosby Inc.; 2002: 446.

Gupta NK, de Lemos JA, Ayers CR, Abdullah SM, McGuire DK, Khera A. The relationship between C-reactive protein and atherosclerosis differs on the basis of body mass index. J Am Coll Cardiol. 2012;60(13). Available at http://content.onlinejacc.org. Accessed February 22, 2013.

Ho JS, Cannaday JJ, Barlow CE, Reinhardt DB, Wade WA, Ellis JR. Utility of high-sensitivity C-reactive protein versus coronary artery calcium for the detection of obstructive stenoses in stable patients (abstract). Am J Cardiol February 1, 2013: 111(3):328–332. Accessed February 22, 2013.

Klotter J. The rosuvastatin-JUPITER controversy. Townsend Lett. May 2012;346:23–24.

The Challenges of Determining Hypertension

“The current approach to define normal [blood pressure] as less than 120/80 is presumably based on detectable increases in risk above that level,” say Brent C. Taylor, PhD; MPH, Timothy J. Wilt, MD, MPH; and H. Gilbert Welch, MD, MPH. “ …  [but] the threshold to label individuals as ‘abnormal’ ought to require more than simply any detectable effect, in any outcome, in any size sample.” Treatment for above-normal blood pressure typically involves medications. A lower cut-off for normal means that more people are treated, potentially leading to more adverse drug effects and higher medical costs. More treatment does not necessarily reduce mortality. In their 2011 research article for the Journal of General Internal Medicine, Taylor, Wilt, and Welch argue, “ … the definition of normal blood pressure must be made with careful attention to the trade-off between the desire to identify those at substantially higher risk than average and the need to avoid overdiagnosis and overtreatment.” This leads back to the question: What is normal?

In an effort to determine normal blood pressure linked to mortality outcomes, Taylor, Wilt, and Welch decided to investigate the independent effects of diastolic and systolic blood pressure on mortality by using data collected during the first National Health and Nutrition Examination Survey (NHANES I) in the early 1970s. The NHANES I subjects were followed for two decades. Taylor and colleagues chose to use the oldest data that they could find in order to avoid the confounding effect of hypertension treatment as much as possible.

Taylor and colleagues obtained data for 6839 adults whose blood pressure (BP) was taken by a physician at the beginning of a physical exam and twice by nurses at the exam’s end. An individual’s three BP readings tended to be about the same: systolic blood pressure readings taken at exam’s end were an average of 1.5 mm Hg lower than the initial reading, and diastolic pressure readings were an average of 1 mm Hg higher. Taylor and colleagues distributed patients’ systolic reading into seven categories: <100 mm Hg, 100–119 mm Hg, 120–139 mm Hg, 140–159 mm Hg, 160–179 mm Hg, 180–199 mm Hg, ≥200. They distributed diastolic blood pressure reading into eight categories: <60 mm Hg, 60–69 mm Hg, 70–79 mm Hg, 80–89 mm Hg, 90–99 mm Hg, 100–109 mm Hg, 110–119 mm Hg, ≥120. After adjusting for several confounders (age, smoking weight and height, BMI, total cholesterol, education, income, race), Taylor and colleagues compared the all-cause mortality rate for each blood pressure category with the “so-called ‘normal’ blood pressure: less than 120/80.”

The results showed an age-based difference in the correlation between blood pressure levels and overall mortality risk. In people over age 50, significant increases in mortality were associated with a systolic pressure above 140. Diastolic pressure had no significant effect on mortality rates in people over 50. For people 50 years or younger, diastolic pressure ≥100 mmHg or systolic blood pressure ≥200 mmHg was “associated with significant increases in mortality.” Systolic blood pressure between 140 and 200, in the younger group, made “no significant difference in the relative rate of death” when diastolic pressure under 100.

While the authors are not saying that their findings should lead to a change in the definition of normal blood pressure and hypertension, they do suggest that the current normal may be leading to unnecessary treatment expenses and adverse drug effects in millions of people. “We … recognize that our approach for defining normal adds an additional complexity to the current approach because it is modified by age … ” they write. “But even a small simple expansion in the definition of normal – from under 120/80 to under 140/90 – would have a tremendous impact: affecting about 80 million Americans.” “Normal” is the bull’s-eye that practitioners aim for in treatment. “When abnormal is defined to include values in which the risk itself is ambiguous, the ability of treatment to change that risk becomes even less certain,” the authors state. They hope that their findings will be taken into consideration as JNC works on its eighth report on high blood pressure, now in progress.

The definition of normal is one factor in identifying hypertension, but actual measurement is another. Benjamin J. Powers, MD and colleagues report, “There is no consensus among clinical guidelines and quality-reporting standards on the setting, timing, and total number of BP measurements that should be used for classifying patients and making treatment decisions.” The Joint National Committee presently recommends at least two clinical blood pressure readings on separate days in order to make a diagnosis; but that does not take into account the “white coat syndrome,” in which a patient’s blood pressure increases during office visits, nor does it suggest how best to monitor treatment outcomes. The American Society of Hypertension and the European Society of Hypertension advocate the use of home BP monitoring for people with known or suspected hypertension. These societies recommend using a minimum of 12 home readings for clinical decisions.

A 2011 study, led by Powers, investigated the question, where and how many measures? The researchers followed 444 veterans with hypertension for 18 months using clinical, research, and home measurements. The clinical measurements were taken by nurses using Alaris automated devices during routine visits. Researchers used BpTRU digital BP monitors to take two measurements, 5 minutes apart, at baseline, 6, 12, and 18 months. Patients themselves took at least three measurements per week using A&D digital home BP monitors. Patients were shown how to use the monitor and then how to transmit the time-stamped measurement via a telemedicine device and toll-free telephone number to a secure server.

Mean blood pressure measurements taken at the three locations varied greatly, affecting diagnosis and clinical decision-making: “The proportion of patients who had control of his or her SBP in the first 30 days (<140 mm Hg for clinic or research measurement; <135 mm Hg for home measurement) differed between method of measurement: 28% were in control according to clinic measurement, 47% were in control according to home measurement, and 68% were in control according to research measurement.” Overall, mean home systolic blood pressure (SBP) was 9.6 mm Hg less than mean clinical measurement.

Because of natural individual variations in blood pressure as well as the difference between clinic and home measurements, the authors recommend reimbursement for home BP monitors so that multiple measures can be taken and recorded. An average of at least five or six measurements, taken on different days, is needed to give a more accurate view of a patient’s need for hypertension treatment. “Patients could not be classified as having BP that was in or out of control with 80% certainty on the basis of a single clinic SBP measurement from 120 mm Hg to 157 mm Hg,” the authors state. (Multiple measurements taken within minutes did not vary significantly.) The researchers recognize that averaging multiple measurements is problematic for busy practitioners; “If providers are supposed to rely more on average measurements, new ways of capturing and presenting these data at the point of care are needed.”

Powers BJ, Olsen MK, Smith VA, Woolson RF, Bosworth HB, Oddone EZ. Measuring blood pressure for decision making and quality reporting: where and how many measures? Ann Intern Med. 2011;154:781–788. Available at http://annals.org. Accessed February 22, 2013.

Taylor BC, Wilt TJ, Welch HG. Impact of diastolic and systolic blood pressure on mortality: implications for the definition of “normal.” J Gen Intern Med. 2011;26(7):685–690. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC3138604/pdf/11606_2011_Article_1660.pdf. Accessed February 22, 2013.

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 (age 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 DVD 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 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 http://circ.ahajournals.org. 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 www.nejm.org/doi/full/10.1056/NEJMoa1200303. 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 www.link.springer.com/article/10.1007/s12011-013-9627-6. Accessed March 13, 2013.

Blank T. Fluoride & arterial calcification. July 2012. Available at www.fluoridealert.org/studies/cardio02/. 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 http://files.meetup.com/1755143/Association_of_vascular_fluoride_uptake_with%2031.pdf. 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 http://www.ncbi.nlm.nih.gov/pubmed/20012382. 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 www.pagepress.org/journals/index.php/hi/article/viewFile/2888/3139. 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. They then 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 α-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 www.bmj.com/content/346/bmj.e8707. Accessed February 25, 2013.

Study raises questions about dietary fats and heart disease guidance [online article]. BMJ. February 5, 2013. www.group.bmj.com/group/media-latest-news/study-raises-questions-about-dietary-fats-and-heart-disease-guidance. Accessed February 25, 2013.

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. http://summaries.cochrane.org/CD006742/benefits-of-antihypertensive-drugs-for-mild-hypertension-are-unclear. 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 www.nhlbi.nih.gov/guidelines/hypertension/express.pdf. Accessed February 25, 2013.

Neale T. Benefits iffy for drugs in mild hypertension [online article]. MedPage Today. August 16, 2012. www.medpagetoday.com/Cardiology/Hypertension/34225. Accessed March 13, 2013.