Resting ECG and Basic Interpretation Tips

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Ramaz Mitaishvili, MD

Earlier and More Aggressive LDL Lowering, or Better Approaches for Targeting High-Risk Individuals?

A new review by three renowned experts in cardiology suggests that efforts to treat elevated cholesterol levels are not exploiting the full potential of cholesterol-lowering strategies, and current approaches to treatment are simply doing "too little, too late. [1]" The evidence, say these experts, is strong enough to support even more aggressive use of lipid-lowering therapies and to intervene at earlier stages in the development of atherosclerosis.

Writing in the August 5, 2008 issue of Circulation, Drs Daniel Steinberg, Christopher Glass, and Joseph Witztum (all from the University of California, San Diego [UCSD]) point out that the National Institutes of Health (NIH) now recognizes that for individuals at high risk, treatment to LDL-cholesterol levels <70 mg/dL is better than previously recommended targets of <100 mg/dL. The researchers suggest, however, that treating to LDL-cholesterol levels to between 40 and 60 mg/dL confers even more benefit.

"With combination therapy, it is now possible to reach these low LDL goals; they are not unrealistic," write Steinberg, Glass, and Witztum. "Yet, most patients outside specialty clinics are not reaching those goals, in part because of poor compliance but also in part because practitioners are still hesitant to be more aggressive. There continue to be concerns about safety and side effects, despite the wealth of evidence that they are not serious problems in the vast majority of patients."

In terms of clinical management, adults with existing coronary heart disease or multiple risk factors should strive to lower their LDL-cholesterol levels to <50 mg/dL. In fact, the authors write that on the basis of the accumulated evidence, it "would be reasonable to recommend that an 'ideal' LDL-cholesterol level should be defined as <50 mg/dL."

Can You do Better Than Simply Lowering LDL Cholesterol?


Commenting on the proposals of the UCSD researchers, Dr Prediman Shah (Cedars-Sinai Health Center, Los Angeles, CA) told heartwire that he agrees with many of their arguments, especially that earlier and more aggressive treatment in childhood and adolescence, specifically through lifestyle modifications, might be the way to further reduce cardiovascular events from atherosclerosis.

"The problem with that approach, however, is a practical one," said Shah. "We won't be around to see the benefits of those interventions begun in childhood. It will take 30 or 40 or 50 years to establish the usefulness of those strategies, even though such benefits seem reasonable and plausible. While it is still a worthwhile goal, what do we do with the millions of people who have disease and need something done now?"

In their paper, Steinberg, Glass, and Witztum point out that atherosclerosis is often well under way by the time an individual is 30 years old, with fatty-streak lesions evident but asymptomatic and clinically nonthreatening. They argue, however, that intervention should not be deferred until later years--with treatment catching up to the disease--but rather started early because atherosclerosis is a single disease entity that evolves over time. If the disease is a continuum, then treating these fatty streaks will prevent or slow the progression of later, clinically significant lesions.

"Why not slow things down early in the game?" they ask. By eliminating age from risk-prediction models, this would be one way to encourage earlier intervention in patients with high-risk profiles, they add.

Although a long-range plan focusing on prevention at a very early age is appropriate, Shah said there exists a sizable challenge in the current patient population where statin therapy alone is only modestly effective in reducing cardiovascular events. Researchers need to look to other paradigms of management that are applicable now or those next-generation therapies on the horizon within the next five or seven years, such as HDL-based or immunomodulation therapies. Steinberg, Glass, and Witztum agree that these therapies might one day be used alongside cholesterol-lowering agents, but there are ample existing data that show statins and other agents have not been utilized to their full potential and can be put to work to further decrease the risks of hypercholesterolemia.

What About apoB and Other Markers of Risk?


On the proposed push toward an ideal LDL-cholesterol target of <50 mg/dL, Dr Allan Sniderman (McGill University, Montreal, QC) told heartwire that this is an extreme and overly simplistic approach to managing elevated cholesterol levels and the risk of coronary heart disease. Clinicians simply are unable to get patients to such a low treatment target, and in trying to do so, will be prescribing too much medication for too many people. Instead, said Sniderman, the focus should be on using technology to more precisely identify at-risk individuals who would benefit from lower LDL-treatment targets.

Sniderman is a proponent of measuring apolipoprotein B (apoB), as it is a surrogate of the number of atherogenic particles, including very low-density cholesterol (VLDL) and LDL cholesterol, rather than LDL cholesterol, which is a surrogate for the cholesterol concentration of the LDL particle. He believes that Steinberg, Glass, and Witztum are wrong in declaring war on LDL cholesterol and the existing treatment targets.

"I think we would end up using all of the resources in healthcare in a frantic way," said Sniderman. "I think we should try to identify ways in which to make society healthier, but in medical terms, I think we need better ways to identify high-risk people. They don't mention apoB, which is unfortunate, because I don't think there is much doubt that apoB identifies high-risk people more precisely than LDL cholesterol. That's not really debatable at this point. Why wouldn't we use better technology to identify fewer people to treat?"

The American Diabetes Association (ADA) and American College of Cardiology (ACC), said Sniderman, have begun to recognize the value of apoB as a marker of cardiovascular risk, and with the price of the assay coming down, it should start to be used more frequently as a means of identifying high-risk patients. "It's the same biology, just more precise," he said. "So why wouldn't we want to do better, target the patients better? The real benefit comes from making sure you are treating the high-risk patient and get them down to a low level."

Like Steinberg, Glass, and Witztum, Sniderman agrees that at present, short-term strategies based on 10-year risk models result in treating people too late. "Because of the effects of exposure, if we can identify the high-risk person earlier, then we can make very substantial changes in outcome by intervening moderately earlier in life," he said.

Steinberg D, Glass CK, Witztum JL. Evidence mandating earlier and more aggressive treatment of hypercholesterolemia. Circulation 2008; 118: 672-677. Abstract




Reviewed by Ramaz Mitaishvili, MD

Statins Help With Obesity-Related Plaque Progression After Heart Surgery

As body mass index (BMI) increases, the likelihood that atherosclerosis will progress after coronary artery bypass grafting (CABG) also rises, US researchers report. However, aggressive statin therapy may eliminate this association.
Prior research has established obesity as a clear and major risk factor for heart disease, but whether it also affects disease progression post-CABG was unclear, Dr. Christine C. Wee, from Beth Israel Deaconess Hospital in Boston, and colleagues point out.

The researchers addressed this question in 1314 subjects enrolled in the Post CABG trial, which looked at the effects of warfarin and statin therapy following heart surgery. Of the subjects, 254 had a BMI of 30 to 34.9 (class I obesity) and 68 had a BMI of 35 or higher (class II or III).

Angiographic evaluation at 4 to 5 years post-CABG revealed a direct link between BMI and the odds of atherosclerotic progression, according to the report in the Journal of the American College of Cardiology for August 19. Higher BMI, however, did not correlate with an elevated risk of clinical events.

In patients on low-dose lovastatin (2.5 to 5 mg/day), class I obesity and class II or III obesity increased the odds of disease progression by 1.34- and 2.97-fold, respectively (p for trend = < 0.001).

By contrast, obesity was not significantly tied to progression in patients taking high-dose lovastatin (40 to 80 mg/day). In fact, with high-dose lovastatin on board, there was a suggestion that higher BMI actually protected against clinical events (p = 0.06).

The results, the researchers conclude, suggest that "aggressive treatment with (lovastatin) and potentially with other statins may reverse the adverse effect of obesity on coronary artery disease progression. Future studies should examine whether the larger benefits of statins in obese persons generalize to those without pre-existing coronary disease."

J Am Coll Cardiol 2008;52:620-625.








Reviewed by Ramaz Mitaishvili, MD

Survival and Functional Outcomes Good After Surgery for Ebstein Anomaly

Most patients who undergo surgery for Ebstein anomaly have good long-term survival and functional outcomes, according to a report in the August 5th issue of the Journal of the American College of Cardiology.

Many patients require operation for Ebstein anomaly, a spectrum of tricuspid valvular and right ventricular dysplasia, in order to improve their quality of life, the authors explain.

Dr. David J. Driscoll and colleagues from the Mayo Clinic and Foundation, Rochester, Minnesota assessed the long-term functional outcome and reproduction of 285 patients with Ebstein anomaly who underwent surgery at a mean age of 24.

At 10 and 20 years, 82% and 56% of patients, respectively, were alive without having had any reoperation, the authors report. Similarly, 68% (at 10 years) and 35% (at 20 years) of patients had been free of rehospitalization for cardiac causes.

Most patients were in NYHA functional class I (43%) or II (40%), with only a minority in class III (12%) or IV (4%), the researchers note, and half the subjects reported their exercise tolerance to be at least that of their peers.

Overall, outcomes were rated excellent in 7.4%, good in 72.3%, and poor in 20.4% of patients.

About 80% of female patients reported at least one pregnancy, and miscarriage rates were lower after surgery (19%) than before surgery (33%).

Of the 232 liveborn children, 9 were reported to have a heart defect (6 born to mothers and 3 born to fathers with Ebstein anomaly), the investigators report.

"Assessment of the late results of novel methods to repair the tricuspid valve is required," the authors note. "A more durable biological prosthesis is needed for patients whose valves are irreparable."

"The time appears to have arrived for systematic testing of the adjunctive surgical strategies of right ventricular volume reduction surgery, cavopulmonary connection, and prophylactic atrial arrhythmia surgery," writes Dr. Glen Van Arsdell, at the Hospital for Sick Children, University of Toronto, Ontario, Canada, in a related editorial. "They hold the potential for reducing late problems of atrial arrhythmia and right ventricular myopathy."

J Am Coll Cardiol 2008;52:460-469.








Reviewed by Ramaz Mitaishvili, MD

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