June 16th, 2014

Case: Smoking-Related CV Risk and the Need for Statin Therapy in a Former Smoker Who Quit Long Ago

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A 66-year-old white woman without any significant medical history is seen for cardiovascular risk assessment. She has a blood pressure of 100/60 mm Hg, a total-cholesterol level of 210 mg/dL, and an HDL-cholesterol level of 40 mg/dL. She has no history of diabetes; her current fasting glucose is 87 mg/dL. She smoked one pack of cigarettes per day for 20 years, but she quit 15 years ago. Her father had a myocardial infarction at age 69.

She would like to know whether medical therapy is indicated to reduce her risk for atherosclerotic cardiovascular disease (ASCVD).

According to the Pooled Cohort Risk Equations calculator, her 10-year risk for ASCVD is 4.5% if she is considered a nonsmoker; however, when her smoking history is considered significant, the risk finding rises to 8.0%. (The distinction is important, as statin therapy is not recommended for the former group, but initiation of moderate-to-high intensity statin therapy [or at least a discussion of the possibility] is recommended for the latter.)

Questions:

1. How do you think this patient’s history of smoking affects her overall cardiovascular risk? How long after quitting does a longtime smoker’s smoking-related risk no longer contribute to his or her overall risk burden?

2. Would you check any other risk factors or other indicators to further evaluate this patient’s risk?

3. What else, if anything, would you do?

 

Response:

Neil J. Stone, MD

This instructive case illustrates the value of discussing risk with primary-prevention patients for whom quantitative risk determination is uncertain. The emphasis on this type of discussion is one of the new features of the 2013 prevention guidelinesthat primary care physicians tell me they especially appreciate.

This patient’s smoking history is of concern. Currently, female smokers are as likely as male smokers to die from the many diseases caused by smoking, including heart attack and stroke. The patient says she quit 15 years ago, yet her HDL-cholesterol level is 40 mg/dL, much lower than the average HDL-c level for women (55 mg/dL). One potential explanation for a lower HDL-c level is current cigarette smoking, raising the question of whether she has truly quit. Older studies employing biochemical verification of smoking status after myocardial infarction show substantial rates of ongoing tobacco exposure among people who indicated that they had quit. Thus, this patient should be asked how many cigarettes she has smoked in the past 30 days, not simply whether she has stopped smoking. An astute clinician might also ask her whether she lives with a smoker, given that evensecondhand smoke can increase the risk for smoking-related problems, including stroke and coronary artery calcification (CAC). If we assume that she has truly quit, we can consider the Framingham Heart Study’s finding, 40 years ago, of a drop in rates of coronary heart disease (CHD) and total mortality among men who quit smoking. The CDC also suggests that CHD risk declines within 1 to 2 years after quitting.

(This patient’s low HDL-c level could also, in theory, reflect genetics or the metabolic syndrome. Although we would need to know her waist circumference and triglyceride level to evaluate her for the metabolic syndrome, her low blood pressure and low-normal fasting glucose do not support this diagnosis.)

In the end, the new 2013 prevention guidelines would recommend a clinician–patient discussion in this case. The goal is to address all relevant risk factors, endorse optimal lifestyle changes, and (in selected patients) consider additional factors to determine whether the potential benefit from a statin outweighs the downsides of such therapy. These extra factors — family history of premature ASCVD, LDL-c ≥160 mg/dL, hs-CRP ≥2.0 mg/L, CAC ≥300 Agatston units (or 75th percentile based on age, race, and sex), ankle–brachial index (ABI) <0.9 — may be useful to assess in older individuals such as this patient. Finally, the discussion should ascertain the patient’s preference after she has been adequately informed of the risks and benefits. For example, she may prefer greater adherence to optimal lifestyle changes, including avoidance of tobacco exposure, in which case no further workup would be required.

Of course, the patient may have additional concerns. Although the guidelines list a family history of premature ASCVD as a factor that can alter the risk decision, her father’s MI in his late sixties would not be considered premature. Again, asking her whether her father had positive stress tests or angina in his fifties, and whether he had siblings with premature CHD, could affect how family history influences the decision.

Overall, in a case like this (when a risk decision is uncertain), the 2013 guidelines would recommend considering three factors to inform the risk decision:

a. CAC score: The clinician and this 66-year-old patient might decide that, if she truly has not smoked since 15 years ago, the radiation risk to see if the CAC score is zero would be acceptable — and that statin therapy is not needed;

b.  ABI, which may be useful in detecting peripheral vascular disease in a former smoker;

c. Determining whether hs-CRP is ≥2.0 mg/L:  The JUPITER trial enrolled women 60 years or older, with elevated hs-CRP is elevated and LDL-c is <130 mg/dL.  JUPITER showed a benefit of rosuvastatin in men and women without diabetes or atherosclerotic cardiovascular disease at entry.

The clinician–patient discussion, as outlined above, can synthesize the best current evidence, the clinician’s judgment, and the principle of shared decision making with the patient.

 

Response:

James Fang, MD

How do you think this patient’s history of smoking affects her overall cardiovascular risk? How long after quitting does a former smoker’s smoking-related risk no longer contribute to her overall risk burden?

A history of smoking affects CV risk, but the effect is not as great as current smoking. Moreover, that risk declines with time, and endothelial function does improve with smoking cessation when assessed a year later. How long does it take to no longer contribute to overall risk burden?  That question is difficult to pin down; 3 years after an MI, the risk for recurrent MI falls to a nonsmoker’s risk with smoking cessation. Some people note that CV risk drops by 50% after a year. It is probably more relevant to ask whether or not the patient has atherosclerosis precipitated by past smoking, as I discuss below.

Would you check any other risk factors or other indicators to further evaluate her risk?

I would consider other surrogates for evidence of atherosclerosis (e.g., ABI, hs-CRP, CAC). If atherosclerosis is present, the threshold to consider statin therapy would be lower and may also prove to motivate the patient for lifestyle changes and statin therapy.

What else, if anything, would you do?

Continued emphasis on smoking abstinence and lifestyle changes should be part of the patient’s regular follow-up.

 

Follow-Up:

July 3, 2014

Jay D. Shah, MD

In the end, the decision was made to further risk-stratify the patient by ascertaining her high-sensitivity CRP level, which turned out to be 2.2 mg/L. Rosuvastatin, 20 mg daily, was initiated. Approximately one week after starting statin therapy, the patient developed severe, diffuse myalgias, and the statin was discontinued. For now, the patient will forgo statin therapy and focus on lifestyle modification (exercise and weight loss).

6 Responses to “Case: Smoking-Related CV Risk and the Need for Statin Therapy in a Former Smoker Who Quit Long Ago”

  1. Matthew Carr, MD says:

    do a calcium score and if over 50 would give a statin

  2. Uffe Ravnskov, MD, PhD says:

    There are three simple facts that tell us not to prescribe statin treatment to this woman, or for that matter to any women at all.

    Already in 1992 a meta-analysis supported by the National Heart, Lung, and Blood Institute including more than 124,000 women from six countries showed that high cholesterol is not a risk factor for women (1).

    No cholesterol-lowering trial has succeeded in prolonging the life for women.

    A recent randomized, controlled statin trial performed by researchers independent on the drug industry showed that after six months treatment “4 in 10 treated women cited worsening in either energy or exertional fatigue; 2 in 10 characterized both as “worse” or either as much worse and 1 in 10 characterized both components as much worse” (2).

    1. Jacobs D et al. Report of the Conference on Low Blood Cholesterol: Mortality Associations. Circulation 1992;86:1046-60.
    2. Golomb B et al. Effects of statins on energy and fatigue with exertion: Results from a randomized controlled trial. Arch Intern Med 2012;172:1180-2.

  3. Karen Politis, MD says:

    My “gut feeling” is that this lady can probably be considered a non-smoker, unless she is particularly prone to pulmonary or peripheral vascular disease, in which case the 20 years of one pack may have already left signs of permanent damage. Does she exercise with no symptoms? Is her weight normal? Besides her father, are there other close blood relatives with severe cardiovascular disease?
    As Dr. Ranskov pointed out, side effects of statins might lead to side effects that are worse than the risk, especially if this lady is slim and athletic.

  4. David Powell , MD, FACC says:

    Cardiovascular risk from smoking is cut in half by 5 years of abstinence, and risk returns to that of nonsmokers by 15 to 20 years. Hence, I would consider her a nonsmoker. The family history is not premature. I also educate re utility of CAC scoring for further risk stratification.

  5. To use HS-CRP as the determinant to initiate statin for this woman is a mistake. The Jupiter study failed to demonstrate that treating subjects with elevated HS-CRP was any more productive than treating subjects with normal HS-CRP. That said, further risk stratification is needed.

    I find MESA to provide many answers for us, and as an NIH funded, not industry funded study, the results are more objective.

    In MESA, 90% of the women were considered “low risk” by conventional risk factor assessment. However 30% of these “low risk” women had coronary calcium on CT imaging and follow-up proved that they were at significantly higher risk than their cohorts with score of 0.

    A “Jupiter equivalent” subset of MESA was evaluated. Of these subjects with normal LDL but elevated HS-CRP, 50% had calcium scores of 0 and exhibited almost no events during the follow up. 25% of these subjects had scores in the top quartile and represented the great majority of coronary events on follow up. Those in the second highest quartile demonstrated an increase in heart attacks compared to those with a score of 0, however they could have been given the option of non-drug management.

    A fact from MESA that people seem to forget is the reality that the average baseline HS-CRP was lower in the subset with subsequent heart attacks than in those without. ASCOT-LLA found no correlation between baseline HS-CRP and subsequent results and no correlation between follow up HS-CRP and residual risk. Why we continue to consider HS-CRP to be a good tool in primary prevention is a mistery to me.