November Newsletter
In This Issue
Meds Before Bed
Outrun Your Genes!
Can a Lift a Day Keep Cancer Away?
A Better Model of Medical Care
Old-fashioned medicine with 21st Century convenience and technology
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I hope this newsletter finds you and your family well. I was talking to a friend the other day who told me that she was "so done with winter". I laughed as we discussed that it's technically still fall. As we enter the holiday season, I hope that all of you have a chance to spend time with loved ones. Happy Thanksgiving!
What if a medication could lower your risk of a cardiovascular even by 45%. Would you be interested? What if I told you that there was a simple behavior you could do that wouldn't involve taking more medication that could reduce your risk that much. Oh yeah, it's free. Interested now? The first article has information that anyone with high blood pressure or has a loved one who has high blood pressure will want to read. 

It's in my genes. That's why we look the way we do. Many diseases have a genetic predisposition as well. One of these is depression. Over 7% of Americans will have a major depressive episode and there is a genetic predisposition. Are there ways to prevent this? Can we literally out run our depression genes? The second article gives us the answer. 

One of the major concerns people have with aging is cancer. Cancer will affect all of us either directly or indirectly through loved ones. We know that exercise is good for us when we have been diagnosed with cancer but is there a type of exercise that we can do to make treatment more effective and even prevent cancer? Some interesting research suggests that this may be the case. 

Click on the links the the left to check out our  web site .
Meds Before Bed
Taking hypertension medications before bed improves cardiovascular risk reduction
People have generally been told to take their blood pressure medication during the day, typically in the morning. The thought was that blood pressure is the highest during the day so this would be when you would need the medication the most. When we sleep, our blood pressure tends to drop and this would be the best time to have the effects of the medication at their lowest. However, there tends to be a morning surge in blood pressure and there is a known increased in heart attacks and strokes in the early morning hours. The Hygia Chronotherapy Trial was designed to answer the question of whether we should take blood pressure medications in the morning or at night. The study had over 19,000 patients enrolled with half taking their medication in the morning and half taking it at night. The median follow up was 6.3 years. After adjustment for confounding factors, the results showed an remarkable 45% reduction in the main cardiovascular outcomes which included heart attacks, strokes, cardiovascular death, need for bypass surgery and heart failure. 

  • Aims: The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.
  • Methods and results: In this multicentre, controlled, prospective endpoint trial, 19,084 hypertensive patients (10,614 men/8470 women, 60.5 +/- 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome [0.55 (95% CI 0.50-0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34-0.56)], myocardial infarction [0.66 (0.52-0.84)], coronary revascularization [0.60 (0.47-0.75)], heart failure [0.58 (0.49-0.70)], and stroke [0.51 (0.41-0.63)].
  • Conclusion: Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.
This large study had some pretty remarkable findings. If i was presenting a new medication that reduced the risk of adverse cardiac outcomes by 45%, it would be hailed as a huge breakthrough. This study compared a simple change in timing of taking a dose of medication which costs nothing to get this incredible outcome. In looking at reviewed of the article, I have seen some criticisms of their bio statistics. While this could alter things a bit I certainly don't think it would void the findings. Remember, the most important thing in taking blood pressure medication is to actually take the blood pressure medication. However, if you are able, it certainly makes sense to take blood pressure medications at night. I don't see any downside and the possible improvement in outcome is certainly worth it.  

Outrun Your Genes!
Exercise lowers risk of depression even if you are genetically predisposed

This study examined genomic data from 7,968 individuals seeking to examine the correlation between physical activity and the risk of depression in the context of genetic predisposition. They found that genetic risk correlated with increased odds of depression and physical activity had a negative correlation with depression. Regardless of level of genetic predisposition, higher levels of physical activity correlated with reduced odds of depression. 


  • Background: Physical activity is increasingly recognized as an important modifiable factor for depression. However, the extent to which individuals with stable risk factors for depression, such as high genetic vulnerability, can benefit from the protective effects of physical activity, remains unknown. Using a longitudinal biobank cohort integrating genomic data from 7,968 individuals of European ancestry with high-dimensional electronic health records and lifestyle survey responses, we examined whether physical activity was prospectively associated with reduced risk for incident depression in the context of genetic vulnerability.
  • Methods: We identified individuals with incident episodes of depression, based on two or more diagnostic billing codes for a depressive disorder within 2 years following their lifestyle survey, and no such codes in the year prior. Polygenic risk scores were derived based on large-scale genome-wide association results for major depression. We tested main effects of physical activity and polygenic risk scores on incident depression, and effects of physical activity within stratified groups of polygenic risk.
  • Results: Polygenic risk was associated with increased odds of incident depression,and physical activity showed a protective effect of similar but opposite magnitude,even after adjusting for BMI, employment status, educational attainment, and prior depression. Higher levels of physical activity were associated with reduced odds of incident depression across all levels of genetic vulnerability, even among individuals at highest polygenic risk.
  • Conclusions: Real-world data from a large healthcare system suggest that individuals with high genetic vulnerability are more likely to avoid incident episodes of depression if they are physically active.

Genetic predisposition to different diseases has been highlighted with the advancement of different types of genetic testing. We can now find out if we have genes for cilantro taste
aversion   or how attractive we are to mosquitoes. With depression, studies have shown that up to 40% of observed variation in depression can be explained by genetic difference. People with the highest genetic risk are 50% more likely to be diagnosed with depression. 

This study sought to examine the prospective relationship between physical activity, genetic risk, and incidence of depression. They found that higher levels of physical activity was associated with lowered risk of depression,  regardless  of level of genetic risk. The findings suggest that people at the highest risk may need to exercise more than people at low risk to achieve the same incidence of depressive symptoms. People who engaged in three or more hours of activity per week showed the reduced prevalence of depression and overall they found that 45 minutes or more of daily activity resulted in meaningful reduction in risk of depression. The type of exercise did not seem to be as important as the amount of time spent exercising. Benefits were found both with higher-intensity forms of exercise and lower-intensity exercise (stretching). Cumulative physical activity of any kind has a positive impact on depression risk, even in the presence of genetic factors. So yes, it does appear that at least as far as depression is concerned, we may be able to our run our genes! 

Can a Lift a Day Keep Cancer Away? 
Strength exercise mitigates tumor growth and tumor malignancy development
Cancer is the second leading cause of death in western countries. In recent years research has shown that rather than rest and reduction of physical activity, exercise is not only safe and possible during cancer treatment, it also improves how cancer patients function physically. 

This study examined the effects of strength training on tumor biology. A denocarcinoma models were used to examine the changes in tumor microenvironment promoted by muscular strength training, including cell proliferation and apoptosis, collagen deposit and presence of malignant tumor morphology.  The study demonstrated that strength exercise mitigated tumor growth and favored important tumor endpoints including a lower tumor histological grade, (slowing development of cell aberrant form and division), decreased tumor cell proliferation and lower tumor cell area. In addition, strength exercise stimulated tumor microvessel density, which can enhance the delivery and efficacy of anticancer therapies. In summary, strength exercise mitigated tumor growth and tumor malignancy development. 

  • Purpose: Although resistance exercise (RE) is now recognized as an adjuvant in cancer treatment because of its capacity to prevent muscle wasting, weakness, and cachexia, it is unknown whether RE can mitigate tumor development. Two solid adenocarcinoma models (Walker-256 and Ehrlich) were used to investigate the effects of RE on tumor cell proliferation, growth, and aggressiveness parameters in tumor-bearing animals' life span.
  • Methods: Walker-256 tumor-bearing rats and Ehrlich tumor-bearing mice were subjected to RE, which consisted of climbing a ladder apparatus with loads tied to their tails. After 4 wk, animals were euthanized, and tumors were excised and assessed for tumor microenvironment evaluation such as cell proliferation and apoptosis determination, collagen deposit, and presence of malignant tumor morphology.
  • Results: Our data demonstrate that RE mitigated tumor growth and favored tumor end points such as lower Scarff-Bloom-Richardson histological grade tumor, denoting slow cell aberrant form and division, decreased tumor cell proliferation (evaluated by nucleus marked with antigen ki-67), and lower viable tumor area in both types of tumors studied. In addition, RE stimulated tumor microvessel density in Walker-256 tumor-bearing rats, but there was no change in their life span.
  • Conclusion: RE may mitigate tumor growth and tumor malignancy parameters such as lower histopathological grade, assuming less nuclear pleomorphism and mitotic cells, smaller viable tumor area, and decreased tumor cell proliferation in both adenocarcinomas. In addition, RE induced tumor vascularization.

There has been increasing amounts of research showing the benefits of exercise in treatment of cancers and the American College of Sports Medicine has a consensus statement on Exercise Guidelines for Cancer Survivors . Strength training in particular has been shown to attenuate cancer morbidity and reduce the side-effects of cancer therapies (reduced muscle loss, weakness, and quality of life). But can exercise prevent cancers before they take hold? Can they prevent tumor growth and development? I don't like to typically use studies in my newsletters that are not based on human study, but I found this one compelling. Using two rat models of adenocardinoma, the researchers found that resistance training was able to mitigate the development of the tumor through decreased aggressiveness parameters (grade of tumor, size/area of tumors). Stopping cancers before they start is a great thing and something we should all be interested in for longevity and health. If we do get cancer, this study suggests that strength training can change the tumors to make the treatments we use even more effective. Overall, good reasons to grab some weights!   

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. Feel free to pass this on to anyone you think would benefit from this information. 

You can find previous newsletters archived on my website here


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.