June Newsletter
In This Issue
Does LDL Really Matter?
The PSA Controversy Continues
Revisiting Whole Grains
A New Model of Medical Care
Dr. Niedfeldt
Old-fashioned medicine with 21st Century convenience and technology
Quick Links
Join Our List
View my profile on LinkedIn 
Follow me on Twitter



I hope this newsletter finds you and your family well. I can't believe it is the end of June! The Tour of America's Dairyland is over, Summerfest has started, the Brewers are in town and the weather has been great! Makes me glad to live in Wisconsin. I hope all of you have a great 4th of July weekend. 

Lowering cholesterol has been the main focus in cardiovascular medicine over the past 40 years. LDL cholesterol has been tagged the 'bad' cholesterol and lowering this has been our focus for the past 20+ years. The target for LDL cholesterol has continued to be reduced to the point that now any LDL over 100 is considered high. If someone has had a cardiac event, LDL of 70 (or less) is the recommended goal. But is this correct? Should we be pushing our cholesterol and LDL levels as low as possible? An interesting study below questions the dogma that lower is better when it comes to LDL cholesterol. 


Testing for prostate cancer is a controversial topic. Over the past few years a number of prominent organizations have recommended against screening for prostate cancer using prostate-specific antigen, or PSA. The reasoning is that it leads to overdiagnosis and overtreatment. Is there a role for PSA in assessing risk of prostate cancer? The second article reviews a well-done study that potentially lends some guidelines for use of PSA in screening for prostate cancer. 


The intake of grains has dropped for a number of reasons. More people are finding that gluten has ill effects on them and are avoiding it. Many diet plans have people avoid them. Is this correct? The third study looks at whole grain consumption and risk of various diseases and mortality. I also give some of my take on this. 


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

Does LDL Really Matter?
Inverse relationship between LDL and mortality              
The authors of this study, published in the journal BMJ, reviewed 19 studies of individuals over 60 years of age and investigated the association of LDL-C with mortality. In 16 of 28 cohorts, all-cause mortality was inversely associated with LDL-C, with no association in the remaining 12 cohorts. Cardiovascular mortality was also inversely associated with LDL-C in 2 of 9 cohorts, with no association in the remaining 7 cohorts.
Summary of findings:
  • OBJECTIVE:  It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.  
  • SETTING, PARTICIPANTS AND OUTCOME MEASURES: We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in Individuals >/= 60 years from the general population.  
  • RESULTS: We identified 19 cohort studies including 30 cohorts with a total of 68,094 elderly people, where all-cause mortality was recorded in 28 cohorts and CV mortality in 9 cohorts. Inverse association between all-cause mortality and LDL-C was seen in 16 cohorts (in 14 with statistical significance) representing 92% of the number of participants, where this association was recorded. In the rest, no association was found. In two cohorts, CV mortality was highest in the lowest LDL-C quartile and with statistical significance; in seven cohorts, no association was found.  
  • CONCLUSIONS: High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

OK, let's wrap our heads around this one. This study analyzed several studies and found either no relationship or that there was actually an INVERSE relationship between LDL levels and mortality, both cardiovascular and all cause. This means that lower LDL was associated with MORE cardiovascular deaths and overall death, leading the authors to conclude "this inverse association between LDL and mortality is inconsistent with the cholesterol hypothesis and supports a re-evaluation of treatment guidelines that recommend reducing LDL-C in the elderly as a component of cardiovascular disease prevention strategies". This pretty much blows up everything that we have been told; lower LDL is better. We have seen recommendations go from LDL <160 to <130, to <100. We do have to remember that a ssociation is not the same as causation. However, an inverse association is one of the strongest arguments against causation. It is interesting to see this article in an age where there are some recommending statin medications for everyone. While this is one of a several studies questioning cholesterol levels and their importance in disease there are still some studies suggesting improvement in outcomes with lowered cholesterol. This is why it is so important to take an individualized approach to assessment of cardiac risk. While the jury is still out, I think I'll be taking a pass on that "polypill".

The PSA Controvery Continues...
PSA values in midlife predict future prostate cancer 
prostate cancer

Prostate-specific antigen (PSA) levels are a blood test done to possibly identify prostate cancers. PSA levels in midlife predict future lethal prostate cancer (PCa) risk, according to a study published online June 13 in the Journal of Clinical Oncology
Summary of findings      
  • Purpose:  Prostate-specific antigen (PSA) level in midlife predicted future prostate cancer (PCa) mortality in an unscreened Swedish population. Our purpose was to determine if a baseline PSA level during midlife predicts lethal PCa in a US population with opportunistic screening.
  • Materials and Methods:  We conducted a nested case-control study among men age 40 to 59 years who gave blood before random assignment in the Physicians' Health Study, a randomized, placebo-controlled trial of aspirin and β-carotene among 22,071 US male physicians initiated in 1982 and then transitioned into a prospective cohort with 30 years of follow-up. Baseline PSA levels were available for 234 patients with PCa and 711 age-matched controls. Seventy-one participants who developed lethal PCa were rematched to 213 controls. Conditional logistic regression was used to estimate odds ratios and the area under the receiver operating characteristic curve, with 95% CIs, of the association between baseline PSA and risk of lethal PCa.
  • Results: Median PSA among controls was 0.68, 0.88, and 0.96 ng/mL for men age 40 to 49, 50 to 54, and 55 to 59 years, respectively. Risk of lethal PCa was strongly associated with baseline PSA in midlife: odds ratios (95% CIs) comparing PSA in the > 90th percentile versus less than or equal to median were 8.7 (1.0 to 78.2) at 40 to 49 years, 12.6 (1.4 to 110.4) at 50 to 54 years, and 6.9 (2.5 to 19.1) at 55 to 59 years. A total of 82%, 71%, and 86% of lethal cases occurred in men with PSA above the median at ages 40 to 49, 50 to 54, and 55 to 59 years, respectively.
  • Conclusion: PSA levels in midlife strongly predict future lethal PCa in a US cohort subject to opportunistic screening. Risk-stratified screening on the basis of midlife PSA should be considered in men age 45 to 59 years.

Prostate-specific antigen (PSA) testing is quite controversial at this point in time and there have even been proposed penalties for doctors who order them.There has been a 50% reduction in prostate cancer mortality in the United States, and screening is estimated to account for 45% to 70% of this reduction. However, screening may result in significant harms, including unnecessary biopsies with potential associated adverse effects, overdiagnosis, and resultant overtreatment. Several organizations, including the US Preventive Task Force, recommend against getting PSA tests at all. This has resulted in a 57% decrease in primary care PSA testing over the past few years. Mathematical models project that not screening would eliminate overdiagnosis, but also would result in a doubling of patients presenting with metastatic disease and a 13% to 20% increase in prostate cancer deaths by 2025.

This case-control study of men aged 40 to 59 years
found that overall, 92% of lethal events occurred in men with a PSA above the median (PSA level >1) at age 40 to 49 years. By contrast, men with baseline PSA levels below the median at age 40 to 44 and 45 to 49 years had a 0.19% and 0.51% absolute risk of developing lethal prostate cancer during the next 30 years. 

Based on this, it certainly seems reasonable to use PSA testing possibly even at a younger age to risk stratify and make decisions regarding further testing and prostate cancer surveillance based on these levels. There absolutely should NOT be a penalty for ordering a simple (and cheap) blood test to screen for prostate cancer. There does need to be intelligent use of the information and informed follow up testing and surveillance. If the PSA is less than 1 when tested, there is a very low chance of that man getting a fatal prostate cancer. It is certainly reasonable to do continued surveillance on people who have levels higher than 1. The interval of this follow up isn't clear but it seems that every 2-4 years is a likely reasonable interval. In my opinion, using serial testing over a period of years is a good tool to monitor for prostate cancer in people with higher baseline levels. If I get an elevated PSA result on a serial test, I recheck in a few months prior to sending the patient for a biopsy to again be sure this is not a false elevation. Using this approach has been very effective in my practice. 

Revisiting Whole Grains
Whole grain intake associated with reduced risk of cardiovascular disease, cancer and mortality
This meta-analysis of 45 studies looked at the relative risks of cardiovascular disease, cancer, diabetes, respiratory disease and infectious disease in people consuming a greater than average amount of whole grains and found a decrease in all-cause mortality as well as disease-specific mortality. The biggest improvement was in cardiovascular disease and cancer. 

Summary of findings:   
  • OBJECTIVE:  To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality.  
  • DATA SOURCES: PubMed and Embase searched up to 3 April 2016.  
  • STUDY SELECTION: Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality.  
  • DATA SYNTHESIS: Summary relative risks and 95% confidence intervals calculated with a random effects model. 
  • RESULTS: 45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings-for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I(2)=9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I(2)=56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I(2)=40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I(2)=37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I(2)=83%, n=11) for all causes, 0.78 (0.70 to 0.87; I(2)=0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I(2)=85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I(2)=0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I(2)=79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I(2)=0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular disease and/or all cause mortality, but there was little evidence of an association with refined grains, white rice, total rice, or total grains. 
  • CONCLUSIONS: This meta-analysis provides further evidence that whole grain intake is associated with a reduced risk of coronary heart disease, cardiovascular disease, and total cancer, and mortality from all causes, respiratory diseases, infectious diseases, diabetes, and all non-cardiovascular, non-cancer causes. These findings support dietary guidelines that recommend increased intake of whole grain to reduce the risk of chronic diseases and premature mortality.
This analysis of 64 publications found a dose-responsive effect of whole grain consumption and disease reduction. Those eating 3 servings of whole grains daily had a 19% reduction in coronary artery disease, 22% reduction in cardiovascular disease, 15%  reduction  in cancer, 51%  reduction  of diabetes, and 17% reduction in all-cause mortality. Higher benefits could be seen up to 7+ servings daily. 

There were NO benefits from eating refined grains including white rice. What is a whole grain? This is a grain that contains all the parts of the grain including bran, endosperm  and  germ. Those who know me know that I preach low sugar and starch. This includes processed grains. While this study did look at bread, etc made from whole grain, my recommendation is if you choose to eat grains, try to eat actual grain, not grain ground into flour (bread or pasta). For people who have gluten sensitivity consider quinoa or amaranth. These can be used instead of rice in many dishes or sprinkled on salads or mixed with vegetables. Instead of Cream of Wheat or rolled oatmeal, try steel-cut oats or even better, whole oats. Any of the other whole grains can be substituted as well and don't be afraid to mix several together. To prepare whole grains (available at Outpost and many health food stores) try a rice cooker. Generally around 2 cups water to 1 cup grains works well. They can be refrigerated or even frozen and just heated in the microwave for a quick breakfast or to use instead of rice with another meal. Be careful when adding even whole processed grains to your diet, however. Serving sizes are small (one slice of bread or 1/2 pita). It's easy to overdo it and that can lead to problems with blood sugar. 

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. 


Dogma dies hard. I think that there will be a lot of push back on this study, but this is why we continually look at outcomes. This study looked at the thing that matters most, mortality. Finding an inverse relationship or no relationship between LDL and mortality is not what we would expect to see. It just goes to prove that the science is never settled. 


PSA testing can be done rationally. It's time we stopped the hysterics and got down to rational thoughts on this. This study adds useful information on the thoughtful use of the PSA test. With no screening men will die, and that is not acceptable. 


I'm still not a big fan of even processed whole grains for weight control, but this study helps me to feel better if I do have a pita.


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.