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April Newsletter
In This Issue
More May Be Better
A Vitamin to Reduce Stroke Risk
Does Wording Matter in End-of-Life Care?
A New Model of Medical Care
Dr. Niedfeldt
Old-fashioned medicine with 21st Century convenience and technology
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I hope this newsletter finds you and your family well. It sure is nice to see the sun shining today and I hope it will lead to some consistently warmer weather soon (although living near the lake makes spring tough). I've been out playing catch with my youngest daughter the last few days which really does make it feel like spring. 


The first section looks at a couple of different studies of exercise and mortality. As many of you will recall, I have had a few articles looking at how much exercise is optimum. This month there are two large studies that confirm that some exercise is better than none and more vigorous exercise is better than a little. Check out the details below. 


Are there ways to help prevent strokes? We know that keeping blood pressure under control is probably the most important factors. Two large studies, one from Japan and one from China show that a simple vitamin may also be of benefit in some people. 


Finally, discussing end-of-life issues is probably not on anyone's preferred 'to do' list. The study I am highlighting was designed to look at with wording people preferred for their wishes. However, I think the major point is what their doctor's didn't know about their wishes!  


Click on the links the the left to check out our web site...

More May Be Better

More vigorous exercise shows lowered mortality
Two studies this month, both from JAMA Internal Medicine, examined the effects of exercise and vigorous exercise on mortality. Current physical activity recommendations are to get 150 minutes of moderate-intensity physical activity weekly or 75 minutes of vi gorous-activity weekly. These two prospective cohort studies used self-reported exercise to look for the optimum quantity and intensity of exercise for longevity and found that when it comes to exercise, more (both  duration  and intensity) seems to be better. 


The first study looked at 660,000 adults from the US and Northern Europe and found that some exercise is better than none, and more exercise is even better. A 20% reduction in mortality was found even in those who didn't meet exercise goals, 31% reduction in those who had 1-2 times their exercise goals, 37% in 2-3 times goal, and 39% reduction in those with 3-5 times exercise goal. No harm was found even in those who exercised up to 10 times goal. These lowered mortality rates included deaths from heart disease and cancer. 


Summary of findings:

  • Importance: The 2008 Physical Activity Guidelines for Americans recommended a minimum of 75 vigorous-intensity or 150 moderate-intensity minutes per week (7.5 metabolic-equivalent hours per week) of aerobic activity for substantial health benefit and suggested additional benefits by doing more than double this amount. However, the upper limit of longevity benefit or possible harm with more physical activity is unclear.

  • Objective: To quantify the dose-response association between leisure time physical activity and mortality and define the upper limit of benefit or harm associated with increased levels of physical activity.

  • Design, Setting, and Participants: We pooled data from 6 studies in the National Cancer Institute Cohort Consortium (baseline 1992-2003). Population-based prospective cohorts in the United States and Europe with self-reported physical activity were analyzed in 2014. A total of 661,137 men and women (median age, 62 years; range, 21-98 years) and 116,686 deaths were included. We used Cox proportional hazards regression with cohort stratification to generate multivariable-adjusted hazard ratios (HRs) and 95% CIs. Median follow-up time was 14.2 years. 
  • Exposures: Leisure time moderate- to vigorous-intensity physical activity. 
  • Main Outcomes and Measures: The upper limit of mortality benefit from high levels of leisure time physical activity.
  • Results: Compared with individuals reporting no leisure time physical activity, we observed a 20% lower mortality risk among those performing less than the recommended minimum of 7.5 metabolic-equivalent hours per week (HR, 0.80 [95% CI, 0.78-0.82]), a 31% lower risk at 1 to 2 times the recommended minimum (HR, 0.69 [95% CI, 0.67-0.70]), and a 37% lower risk at 2 to 3 times the minimum (HR, 0.63 [95% CI, 0.62-0.65]). An upper threshold for mortality benefit occurred at 3 to 5 times the physical activity recommendation (HR, 0.61 [95% CI, 0.59-0.62]); however, compared with the recommended minimum, the additional benefit was modest (31% vs 39%). There was no evidence of harm at 10 or more times the recommended minimum (HR, 0.69 [95% CI, 0.59-0.78]). A similar dose-response relationship was observed for mortality due to cardiovascular disease and to cancer.
  • Conclusions and Relevance: Meeting the 2008 Physical Activity Guidelines for Americans minimum by either moderate- or vigorous-intensity activities was associated with nearly the maximum longevity benefit. We observed a benefit threshold at approximately 3 to 5 times the recommended leisure time physical activity minimum and no excess risk at 10 or more times the minimum. In regard to mortality, health care professionals should encourage inactive adults to perform leisure time physical activity and do not need to discourage adults who already participate in high-activity levels.     

The second study followed over 204,000 adults between the ages of 45 and 75 for 8 years, finding again that some exercise is better than none, with 33% reduction in mortality with less than recommended amount, 47% with 1-2 times the amount and 54% with more than twice the recommended amount. Additionally, those who reported more of their exercise to be vigorous had slightly more more benefit than the others. 

Summary of findings:
  • Importance: Few studies have examined how different proportions of moderate and vigorous physical activity affect health outcomes.
  • Objective: To examine whether the proportion of total moderate to vigorous activity (MVPA) that is achieved through vigorous activity is associated with all-cause mortality independently of the total amount of MVPA.
  • Design, Setting, and Participants: We performed a prospective cohort study with activity data linked to all-cause mortality data from February 1, 2006, through June 15, 2014, in 204,542 adults aged 45 through 75 years from the 45 and Up population-based cohort study from New South Wales, Australia. Associations between different contributions of vigorous activity to total MVPA and mortality were examined using Cox proportional hazards models, adjusted for total MVPA and sociodemographic and health covariates.
  • Exposures  Different proportions of total MVPA as vigorous activity. Physical activity was measured with the Active Australia Survey.
  • Main Outcomes and Measures  All-cause mortality during the follow-up period.
  • Results  During 1,444,927 person-years of follow-up, 7,435 deaths were registered. Compared with those who reported no MVPA, the adjusted hazard ratios for all-cause mortality were  0.66 (95% CI, 0.61-0.71; crude death rate, 4.81%), 0.53 (95% CI, 0.48-0.57; crude death rate, 3.17%), and 0.46 (95% CI, 0.43-0.49; crude death rate, 2.64%) for reporting 10 through 149, 150 through 299, and 300 min/wk or more of activity, respectively. Among those who reported any MVPA, the proportion of vigorous activity revealed an inverse dose-response relationship with all-cause mortality: compared with those reporting no vigorous activity the fully adjusted hazard ratio was 0.91 in those who reported some vigorous activity (but <30% of total activity) and 0.87 (95% CI, 0.81-0.93; crude death rate, 2.08%) among those who reported 30% or more of activity as vigorous. These associations were consistent in men and women, across categories of body mass index and volume of MVPA, and in those with and without existing cardiovascular disease or diabetes mellitus.
  • Conclusions and Relevance  Among people reporting any activity, there was an inverse dose-response relationship between proportion of vigorous activity and mortality. Our findings suggest that vigorous activities should be endorsed in clinical and public health activity guidelines to maximize the population benefits of physical activity.

Last month I highlighted a study showing that even low levels of exercise helped reduce belly fat, but that more intense exercise was needed for improvement in glucose tolerance. These two large studies show that more some exercise is significantly better than none, and that more exercise (both amount and intensity) is even better when it comes to death rate from cancer and heart disease. Now, some of you may recall that I highlighted a study showing that too much exercise may be bad for you. My take on all this is that shorter, more intense bouts of exercise may be one of the optimum ways to exercise with additional moderate intensity exercise. An example would be doing resistance training with shorter rest intervals 3-4 times/week (20-45 min) and taking the dog for a 2-3 mile walk daily. But remember, don't get too hung up on the details, anything is better than nothing!    
A Vitamin to Reduce Stroke Risk
Folic Acid found to reduce incidence and mortality


Folic acid has been shown in the past to be beneficial in pregnant women, reducing the incidence of spine and brain defects in their children. It is essential for numerous body functions and must be supplied through the diet to meet daily needs. Low levels of folic acid have also been associated with anemia, weakness, nerve damage, and mental confusion among other findings. 
The two studies I am highlighting show that this inexpensive supplement has a role in prevention of strokes. 

The first study, from Japan, was an observational study of over 72,000 adults without prior stroke or heart attack followed for an average of over 19 years. The use of a multivitamin (containing folic acid) was associated with a lower rate of stroke. This was especially noted among those with low intake of fruits and vegetables. 

The second study was a randomized trial of over 20,000 hypertensive Chinese adults without prior stroke or heart attack. These people were randomized to receive an anti hypertensive medication with or without folic acid. Overall, folic acid was associated with a significantly reduced risk of stroke in this group. 

Summary of findings:

  • BACKGROUND AND PURPOSE:  An effect of multivitamin supplement on stroke risk is uncertain. We aimed to examine the association between multivitamin use and risk of death from stroke and its subtypes.                  
  • METHODS:  A total of 72,180 Japanese men and women free from cardiovascular diseases and cancers at baseline in 1988 to 1990 were followed up until December 31, 2009. Lifestyles including multivitamin use were collected using self-administered questionnaires. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of total stroke and its subtypes in relation to multivitamin use.
  • RESULTS:  During a median follow-up of 19.1 years, we identified 2,087 deaths from stroke, including 1,148 ischemic strokes and 877 hemorrhagic strokes. After adjustment for potential confounders, multivitamin use was associated with lower but borderline significant risk of death from total stroke (HR, 0.87; 95% confidence interval, 0.76-1.01), primarily ischemic stroke (HR, 0.80; 95% confidence interval, 0.63-1.01), but not hemorrhagic stroke (HR, 0.96; 95% confidence interval, 0.78-1.18). In a subgroup analysis, there was a significant association between multivitamin use and lower risk of mortality from total stroke among people with fruit and vegetable intake <3 times/d (HR, 0.80; 95% confidence interval, 0.65-0.98). That association seemed to be more evident among regular users than casual users. Similar results were found for ischemic stroke.
  • CONCLUSIONS:  Multivitamin use, particularly frequent use, was associated with reduced risk of total and ischemic stroke mortality among Japanese people with lower intake of fruits and vegetables.

The second study was a randomized trial of over 20,000 hypertensive Chinese adults without prior stroke or heart attack. These people were randomized to receive an anti hypertensive medication with or without folic acid. Overall, folic acid was associated with a significantly reduced risk of stroke in this group. 

  • Importance:  Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data.
  • Objective:  To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension.
  • Design, Setting, and Participants: The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20,702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study.
  • Interventions: Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n=10,348) or a tablet containing enalapril, 10 mg, alone (n=10,354).
  • Main Outcomes and Measures: The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death.
  • Results: During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events.
  • Conclusions and Relevance: Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels.

Huo Y, Li J, Qin X, et al. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA. 2015;313(13):1325-1335.


These two studies show us the importance good nutrition in stroke prevention. Now, before you go out to buy a multivitamin or folic acid supplement remember that these studies were done in populations that are often folic acid deficient. China has no programs for folic acid supplementation, where here in the US we do. Of note is that those people in the Japanese study who tended to be low were those who had minimal fruit and vegetable intake. Folate occurs naturally in vegetables (especially the green, leafy type), fruits, nuts, beans, dairy, poultry, meat, eggs, seafood, and grains. 

It is always best to get nutrients from whole foods and most of us should be able to get the folate we need through whole food sources. If there is any doubt, you can certainly take a multivitamin, which will generally supply the 400-800 mcg necessary.  
Does Wording Matter in End-of-Life Care?
Should we "allow natural death" or "do not resuscitate"?


Communication of end-of-life preferences is not as simple as it seems. There are many confusing factors and people's wishes are not always communicated to their loved ones who will be making the decisions. Many people don't know what "do not resuscitate" means. This means do not resuscitate me if my heart stops or I stop breathing. As a physician, I'm not sure what "allow natural death" means without some explanation. Does this allow for antibiotics, blood transfusions, IV fluids? There really is no substitution for sitting down with your loved ones and your physician and going through many of the specific interventions that area possible. When a person becomes ill, there is no substitution for a full discussion of the illness, making sure that everyone understands the reality of the illness and the wishes of the person with the illness. 

Summary of findings:  

  • BACKGROUND: Many patients with advanced cancer at our hospital request full resuscitative efforts at the end of life. We assessed the knowledge and attitudes of these patients towards end-of-life (EOL) care, and their preferences about "Do Not Resuscitate" (DNR), "Allow Natural Death" (AND), and "full code" orders. 

  • METHODS: The first 100 consenting adult patients with advanced cancer were surveyed regarding their diagnosis, prognosis, and attitudes about critical care and resuscitation. They were then presented with hypothetical scenarios in which a decision on their code status had to be made if they had one year, six months, or one month left to live. Half were given a choice between being "full code" and "DNR," and half could choose between "full code" and "AND."

  • RESULTS: All 93 of the participants who completed the survey were considered by their attending physician to have a terminal illness, but only 42% of these interviewees believed they were terminally ill. In addition, only 25% of participants thought that their primary oncologist knew their EOL wishes. Participants were equally likely to choose either of the "no code" options in all hypothetical scenarios (p>0.54), regardless of age, sex, race, type of cancer, education, or income level. A similar proportion of patients who had a living will chose "AND" and "DNR" orders instead of "full code" in all the scenarios (47%-74% and 63%-71%). In contrast, among patients who did not have a living will, 52% chose "DNR," while 19% opted for "AND."

  • CONCLUSIONS: We hypothesized that "AND" orders may be more acceptable to patients with advanced cancer, but there was no statistically significant difference in acceptability between "AND" and "DNR" orders.

What really struck me about this study isn't the discussion of what nomenclature is acceptable for end-of life care wishes, it's that only 42% of people with advanced cancers actually thought they had a terminal illness. This is an absolute failure of our system to properly communicate. Of these people with terminal illnesses, only 25% thought their oncologist knew what their end-of-life wishes were. The result of this lack of communication is loved ones often having to make decisions they are not equipped to make during a crisis situation in an emergency room. Only 46% of the people studied had a living will and 36% had a durable power of attorney for healthcare. 

It's so important that we all take some time to discuss our wishes with our loved ones and our physicians. Write down specifically what you would like. It may seem easy when we are healthy, but reevaluate these wishes with a serious illness and most importantly, let your family and doctor know specifically. Ask questions during an illness. Get another opinion. 

To help with this discussion, here is a link to the State of Wisconsin's Advance Directives page. Here you can find forms for 
Living Will, POA for healthcare, and others. 
Thank you for taking the time to read through this newsletter. I hope you have found this information useful as we work together to optimize your health. 


One of my favorite quotes about diet is from Michael Pollan: "Eat food, not too much, mainly plants". I read a colleague who had this corollary for exercise: "Get some exercise, the more the better, some of it vigorous". I think following these two ideas will lead to a long, prosperous life. 


Folic acid deficiency has been linked to multiple diseases, now including higher incidence of stroke. Although most grains in our country are fortified, I try to have people avoid food out of a box. Instead, eat plenty of green, leafy vegetables and fruits. 


Research shows that cancer patients who discussed end-of-life care with their doctors "suffered less, were physically more capable, and were better able, for a longer period to interact with others". As a profession, physicians need to give people realistic expectations for their treatments and be willing to discuss patient wishes. Patients need to be willing to discuss hard topics with their doctors and families.   


As always, if you have questions about anything in this newsletter or have topics you would like me to address, please feel free to contact me by email, phone, or just stop by! 

To Your Good Health,
Mark Niedfeldt, M.D.