HgbA1c (hemoglobin A1c) predicts prediabetes better than glucose

HgbA1c predicts prediabetesHgbA1c (hemoglobin A1c) is hemoglobin that has been ruined by glycation (bonding with sugar). It has long been recognized as a biomarker for average glucose over an approximately three month time span as well as a metric for the degree of damaging glycation occurring throughout the body. Now further evidence for its superior value as a predictor for prediabetes is presented in a study just published in The Lancet Diabetes & Endocrinology.The authors…

“…compared the risk of future outcomes across different prediabetes definitions based on fasting glucose concentration, HbA1c, and 2 h glucose concentration during over two decades of follow-up in the community-based Atherosclerosis Risk in Communities (ARIC) study. We aimed to analyse the associations of definitions with outcomes to provide a comparison of different definitions.”

HgbA1c compared to fasting and 2 hour glucose

They compared several prediabetes definitions in their ability to predict major long-term health problems. They analyzed data from over seven thousand subjects drawn from four communities across the USA who participated in the Atherosclerosis Risk in Communities (ARIC) study. HgbA1c was pitted against fasting and 2 hour postprandial glucose:

“Fasting glucose concentration and HbA1c were measured at visit 2 and fasting glucose concentration and 2 h glucose concentration were measured at visit 4. We compared prediabetes definitions based on fasting glucose concentration (American Diabetes Association [ADA] fasting glucose concentration cutoff 5·6–6·9 mmol/L and WHO fasting glucose concentration cutoff 6·1–6·9 mmol/L), HbA1c (ADA HbA1ccutoff 5·7–6·4% [39–46 mmol/mol] and International Expert Committee [IEC] HbA1c cutoff 6·0–6·4% [42–46 mmol/mol]), and 2 h glucose concentration (ADA and WHO 2 h glucose concentration cutoff 7·8–11·0 mmol/L).”

HgbA1c better identifies those at risk for diabetes and serious complications

Chronic kidney disease, cardiovascular disease and death were more accurately predicted by HgbA1c than by fasting glucose:

“After demographic adjustment, HbA1c-based definitions of prediabetes had higher hazard ratios and better risk discrimination for chronic kidney disease, cardiovascular disease, peripheral arterial disease, and all-cause mortality than did fasting glucose concentration-based definitions (all p<0·05). The C-statistic for incident chronic kidney disease was 0·636 for ADA fasting glucose concentration clinical categories and 0·640 for ADA HbA1c clinical categories. The C-statistics were 0·662 for ADA fasting glucose clinical concentration categories and 0·672 for ADA HbA1c clinical categories for atherosclerotic cardiovascular disease, 0·701 for ADA fasting glucose concentration clinical categories and 0·722 for ADA HbA1c clinical categories for peripheral arterial disease, and 0·683 for ADA fasting glucose concentration clinical categories and 0·688 for ADA HbA1c clinical categories for all-cause mortality. Prediabetes defined using the ADA HbA1c cutoff showed a significant overall improvement in the net reclassification index for cardiovascular outcomes and death compared with prediabetes defined with glucose-based definitions.”

Clinical Significance

HgbA1c study reviewed in Medscape Family Medicine

Medscape Family Medicine remarks:

“The researchers found that using an HbA1c-based definition, those identified as having prediabetes were 50% more likely to develop kidney disease, twice as likely to develop CVD, and 60% more likely to die from any cause compared with those with normal HbA1c.”

The authors, quoted in Medscape Family Medicine, comment on the practical significance of their findings:

“When someone is told they have prediabetes, we hope it will cause them to make changes to their habits in order to prevent the development of diabetes and its complications,” added the study’s senior author, Elizabeth Selvin, PhD, MPH, a professor in the Bloomberg School’s department of epidemiology.

“Being identified as having prediabetes can also make it easier to receive weight-loss and nutritional counseling as well as reimbursement for these services. Intensive lifestyle changes and weight loss can reduce the risk of diabetes, so it is critically important we identify those persons who are at high risk.

At the same time, we also don’t want to overdiagnose people. Using the hemoglobin A1c test allows us to more accurately identify those persons at highest risk,” she added.

This is important information for physicians and it is also important information for professional organizations. Coming to a global consensus on how to define and diagnose prediabetes would really help move the field forward — and help patients all over the world,” she concluded.”

The authors conclude:

“Our results suggest that prediabetes definitions using HbA1c were more specific and provided modest improvements in risk discrimination for clinical complications. The definition of prediabetes using the ADA fasting glucose concentration cutoff was more sensitive overall.”

Brain blood flow reduction associated with kidney function

Journal of the American Society of NephrologyBrain health requires adequate cerebral blood flow. A study just published in the Journal of the American Society of Nephrology demonstrates that impairments in kidney function consistent with mild CKD (chronic kidney disease) are associated with reduced blood flow in the brain. The authors state:

“CKD is linked with various brain disorders. Whereas brain integrity is dependent on cerebral perfusion, the association between kidney function and cerebral blood flow has yet to be determined.”

So they examined data from the population–based Rotterdam Study that included 2645 participants with an average age of 56.6 years, roughly half men and women. They used eGFR (calculated rate of kidney filtration) and the albumin-to-creatinine ratio to assess kidney function and phase–contrast magnetic resonance imaging of the basilar and carotid arteries to measure cerebral blood flow. The albumin-to-creatinine ratio didn’t pan out when subjected to adjustment for cardiovascular risk factors, but every decrease in eGFR was associated with reduced brain blood flow:

“Participants had an average (SD) eGFR of 86.3 (13.4) ml/min per 1.73 m2 and a median (interquartile range) albumin-to-creatinine ratio of 3.4 (2.2–6.1) mg/g. In age- and sex-adjusted models, a higher albumin-to-creatinine ratio was associated with lower cerebral blood flow level (difference in cerebral blood flow [milliliters per minute per 100 ml] per doubling of the albumin-to-creatinine ratio, −0.31… The association was not present after adjustment for cardiovascular risk factors (P=0.10). Each 1 SD lower eGFR was associated with 0.42 ml/min per 100 ml lower cerebral blood flow (95% confidence interval, 0.01 to 0.83) adjusted for cardiovascular risk factors.”

Implications for blood pressure management

This applies to the general population without overt kidney disease, and clinicians should bear in mind the importance of maintaining adequate cerebral blood flow when managing hypertension and the evidence documenting worse outcomes when blood pressure is medicated too aggressively. According to the authors’ conclusion, even mild CKD may heighten the risk of adverse events such as cognitive impairment, falls and dizziness due to impairments of brain perfusion when blood pressure is forced too low.

“Thus, in this population-based study, we observed that lower eGFR is independently associated with lower cerebral blood flow.”

Low normal sodium a cardiovascular risk

Nutrition, Metabolism & Cardiovascular DiseasesSerum sodium levels are influenced by a number of factors linked to cardiovascular health including dysglycemia (blood glucose disorders), hypothyroid, adrenal dysregulation and others. Research just published in Nutrition, Metabolism & Cardiovascular Diseases identifies low serum sodium within the normal range as a risk predictor for cardiovascular disease and stroke. The authors state:

Hyponatremia, usually defined as serum sodium concentration <136 mEq/L, is one of the most common electrolyte abnormalities observed in hospitalised patients and in patients with chronic kidney disease (CKD), coronary heart disease (CHD) and heart failure (HF). Several clinical and epidemiological studies have shown hyponatremia to be associated with increased total mortality in these patients. More recently, attention has turned to the possibility that mild hyponatremia, may be associated with adverse outcomes in the general population…in the three population studies that have examined the relationship between hyponatremia and mortality in community based subjects, there is evidence that hyponatremia is associated with increased mortality and even a level of sodium concentration in the lower normal range (serum sodium 135-137 mEq/L), a level usually considered benign, is associated with increased mortality.”

Less is known about the association between serum sodium and potassium and the risk of cardiovascular disease and stroke in older men withoutmthese disorders. So the authors examined data for 3099 men aged 60-79 years without a history of cardiovascular disease for an average 11 years. During that time there were 528 major CVD events (fatal coronary heart disease [CHD] and non-fatal MI, stroke and CVD death) and 873 total deaths.

Mildly low sodium is not benign

 Although no association was seen between serum potassium and cardiovascular disease, low serum sodium within the normal range as well as high serum sodium is associated with increased risk of stroke and cardiovascular disease mortality:
“A U shaped relationship was seen between serum sodium concentration and major CVD events and mortality. Hyponatremia (<136 mEq/L) and low sodium within the normal range (136-138 mEq/L) showed significantly increased risk of major CVD events and total mortality compared to men within the upper normal range (139-143 mEq/L) after adjustment for a wide range of confounders and traditional risk factors [adjusted HRs 1.55 and 1.40 for major CVD events respectively and 1.30 and 1.30 respectively for total mortality]. Hyponatremia was associated with inflammation, NT-proBNP, low muscle mass and alkaline phosphatase; these factors contributed to the increased total mortality associated with hyponatremia but did not explain the increased risk of CVD events associated with hyponatremia or low normal sodium concentration. Hypernatremia (>145 mEq/L) was associated with significantly increased risk of CVD events and mortality due to CVD causes.”
In other words, both low normal and high sodium are a significant risk factor for cardiovascular disease and mortality.

Clinical Implications

Practitioner’s should bear in mind the authors’ conclusions and not dismiss low normal serum sodium:
“Hyponatremia and hypernatremia are both associated with increased risk of CVD incidence and mortality. Low sodium within the normal range is associated with significantly increased CVD events and total mortality in older men without major CVD or HF even in the absence of diuretic use and renal dysfunction. The data lends further evidence to the suggestion that the presence of mild hyponatremia is not benign. The findings may have important implications for the monitoring of sodium levels in clinical practice in older adults. The presence of mild hyponatremia in the absence of known causes such as renal dysfunction and diuretics may warrant further investigation in these men to assess CVD risk factors or possible underlying ill-health such as chronic inflammation. Further large studies are required to confirm and elucidate the nature of the association between low normal sodium and risk of incident CVD.”

CKD (chronic kidney disease) expected for 50% over age 30

American Journal of Kidney DiseasesChronic kidney disease (CKD) is rising steeply and projected to affect more than half of those aged 30 to 64 years in the coming twenty years according to a study just published in the American Journal of Kidney Diseases. The authors state:

“Awareness of chronic kidney disease (CKD), defined by kidney damage or reduced glomerular filtration rate, remains low in the United States, and few estimates of its future burden exist…We used the CKD Health Policy Model to simulate the residual lifetime incidence of CKD and project the prevalence of CKD in 2020 and 2030. The simulation sample was based on nationally representative data from the 1999 to 2010 National Health and Nutrition Examination Surveys.”

More than half of people aged 30 to 64 years likely to be affected

The authors’ data showed that…

For US adults aged 30 to 49, 50 to 64, and 65 years or older with no CKD at baseline, the residual lifetime incidences of CKD are 54%, 52%, and 42%, respectively. The prevalence of CKD in adults 30 years or older is projected to increase from 13.2% currently to 14.4% in 2020 and 16.7% in 2030.”

Currently one in seven adults is affected by chronic kidney disease. The public health consequences are enormous. The authors conclude:

“For an individual, lifetime risk of CKD is high, with more than half the US adults aged 30 to 64 years likely to develop CKD. Knowing the lifetime incidence of CKD may raise individuals’ awareness and encourage them to take steps to prevent CKD.”

Prevention: Metabolic syndrome and chronic kidney disease

Current Opinion in Nephrology and HypertensionComponents of metabolic syndrome (MetS) including insulin resistance, hypertension, dyslipidemia and inflammation are particularly rough on the kidneys. A review published in Current Opinion in Nephrology and Hypertension highlights the connection:

“The association of the metabolic syndrome (MetS) with cardiovascular risk, mortality, type 2 diabetes mellitus, stroke, nonfatty liver disease and gout is well known. However, the association of the MetS with chronic kidney disease (CKD) is now emerging…Studies show that patients with MetS have a 2.5-fold higher risk of developing CKD. The risk of microalbuminuria is also increased two-fold in the MetS. Renal dysfunction becomes apparent long before the appearance of hypertension or diabetes in MetS. Compared with healthy controls, patients with MetS have increased microvascular disease-tubular atrophy, interstitial fibrosis, arterial sclerosis and global and segmental sclerosis.”

Clinicians should especially note that metabolic syndrome is contributing to chronic kidney disease well before it evolves into diabetes and the development of hypertension. Regarding potential mechanisms:

“Studies suggest that the renal fibrosis seen in MetS might be caused by a constellation of insulin resistance, hypertension, dyslipidemias and inflammation, and result in a heightened expression of adipocytokines, angiotensin and inflammatory cytokines such as interleukin-6 and tumour necrosis factor-alpha.”

World Journal of NephrologyThe author of a paper published in the World Journal of Nephrology states:

“Despite the ambiguous definition of MetS, it has been clearly associated with chronic kidney disease markers including reduced glomerular filtration rate, proteinuria and/or microalbuminuria, and histopathological markers such as tubular atrophy and interstitial fibrosis. However, the etiological role of MetS in chronic kidney disease (CKD) is less clear. The relationship between MetS and CKD is complex and bidirectional, and so is best understood when CKD is viewed as a common progressive illness along the course of which MetS, another common disease, may intervene and contribute. Possible mechanisms of renal injury include insulin resistance and oxidative stress, increased proinflammatory cytokine production, increased connective tissue growth and profibrotic factor production, increased microvascular injury, and renal ischemia.

PLOS ONEThe authors of a study published in PLOS One on the relation between metabolic syndrome and chronic kidney disease in an adult Korean population came to the conclusion:

“The strength of association between MS [metabolic syndrome] and the development of CKD increase as the number of components increased from 1 to 5. In sub-analysis by men and women, MS and its each components were a significant determinant for CKDMS and its individual components can predict the risk of prevalent CKD for men and women.”

Moreover, they excluded patients with diabetes to more clearly isolate contribution of metabolic syndrome to CKD.

Cardiology Research and PracticeCommenting on the link between metabolic syndrome and chronic kidney disease in the development of cardiovascular disease in a paper published in Cardiology Research and Practice the authors note:

Microalbuminuria has been described as the earliest manifestation of MetS-associated kidney damage and diabetic nephropathy, and it is associated with insulin resistance independent of diabetes. MetS is often accompanied by increased plasma renin activity, angiotensinogen, angiotensin-converting enzyme activity, and angiotensin II (renin-angiotensin-aldosterone system) and with renal sympathetic activity. Hyperinsulinemia, insulin resistance, and increased plasma angiotensin II levels are potent activators of expression of transforming growth factor-β1, a fibrogenic cytokine that contributes to glomerular injury.”

Insulin resistance, of course, spurs chronic inflammation:

“The hallmark of MetS is insulin resistance. Inflammatory mediators, including tumor necrosis factor (TNF)-α, have been shown to mediate insulin resistance. Adipokines, including TNF-α, IL-6, and resistin, are cytokines secreted by adipose tissue, and their plasma concentrations are elevated in patients with MetS, whereas their plasma adiponectin levels are reduced. These findings may contribute to insulin resistance, and insulin resistance promotes chronic inflammation.”

Sugar versus salt in hypertension and chronic kidney disease

Open HeartA striking paper just published in the journal Open Heart (British Cardiovascular Society) identifying sugar as a worse culprit than salt for hypertension and cardiometabolic disease further links metabolic syndrome and chronic kidney disease. The authors note:

“Cardiovascular disease is the leading cause of premature mortality in the developed world, and hypertension is its most important risk factor. Controlling hypertension is a major focus of public health initiatives, and dietary approaches have historically focused on sodium. While the potential benefits of sodium-reduction strategies are debatable, one fact about which there is little debate is that the predominant sources of sodium in the diet are industrially processed foods.”

But processed foods are high in sugar as well as salt, and it may be unwise to aggressively change sodium consumption…

‘Strategies to lower dietary sodium intake focus (implicitly if not explicitly) on reducing consumption of processed foods: the predominant sources of sodium in the diet…Nonetheless, the mean intake of sodium in Western populations is approximately 3.5–4 g/day. Five decades worth of data indicates that sodium intake has not changed from this level across diverse populations and eating habits, despite population-wide sodium-reduction efforts and changes in the food supply.Such stability in intake suggests tight physiologic control, which if indeed the case, could mean that lowering sodium levels in the food supply could have unintended consequences. Because processed foods are the principal source of dietary sodium, if these foods became less salty, there could be a compensatory increase in their consumption to obtain the sodium that physiology demands.

Highly refined carbohydrates, the fuel for metabolic syndrome, worse than salt

This includes fructose:

“Coincidentally, processed foods happen to be major sources of not just sodium but of highly refined carbohydrates: that is, various sugars, and the simple starches that give rise to them through digestion. Compelling evidence from basic science, population studies, and clinical trials implicates sugars, and particularly the monosaccharide fructose, as playing a major role in the development of hypertension. Moreover, evidence suggests that sugars in general, and fructose in particular, may contribute to overall cardiovascular risk through a variety of mechanisms. Lowering sodium levels in processed foods could lead to an increased consumption of starches and sugars and thereby increase in hypertension and overall cardiometabolic disease.”

Hypertensive mechanisms of fructose. NO, nitric oxide; RAS, renin-angiotensin system; RNS, reactive nitrogen species; ROS, reactive oxygen species.

Hypertensive mechanisms of fructose. NO, nitric oxide; RAS, renin-angiotensin system; RNS, reactive nitrogen species; ROS, reactive oxygen species.

 “Although high intakes of either fructose alone or sucrose may lead to insulin resistance, it is fructose that has been implicated as the sugar responsible for reducing sensitivity of adipose tissue to insulin.Insulin stimulates the SNS and hyperinsulinaemia may lead to hypertension, with the degree of insulin resistance in peripheral tissues directly correlated with hypertension severity. Reducing insulin resistance may lead to a reduction in blood pressure, and hyperinsulinaemia seems more related to fructose than glucose.”

The authors make a distinction between fructose added to foods and that found naturally in whole fruit as stated in their conclusion:

“While naturally occurring sugars in the form of whole foods like fruit are of no concern, epidemiological and experimental evidence suggest that added sugars (particularly those engineered to be high in fructose) are a problem and should be targeted more explicitly in dietary guidelines to support cardiometabolic and general health…Evidence from epidemiological studies and experimental trials in animals and humans suggests that added sugars, particularly fructose, may increase blood pressure and blood pressure variability, increase heart rate and myocardial oxygen demand, and contribute to inflammation, insulin resistance and broader metabolic dysfunction. Thus, while there is no argument that recommendations to reduce consumption of processed foods are highly appropriate and advisable, the arguments in this review are that the benefits of such recommendations might have less to do with sodium—minimally related to blood pressure and perhaps even inversely related to cardiovascular risk—and more to do with highly-refined carbohydrates. It is time for guideline committees to shift focus away from salt and focus greater attention to the likely more-consequential food additive: sugar.”

Quoted in Medscape Medical News, Richard Krasuski, MD, from the Cleveland Clinic in Ohio commented on the study:

“”It is a little bit frightening that we have been focusing on salt for so long.”…The conclusion that sugar represents a greater danger to the heart than salt, Dr Krasuski said, was an “eye opener.” He acknowledged, though, that he should have anticipated it. He and other cardiologists have noticed that the recommendations to increasingly lower salt intake have not resulted in the expected positive cardiovascular outcomes.”

Bottom line for chronic kidney disease

CKD incidence is rising steeply and projected to affect half the population aged 30 to 64. Key causal factors are metabolic syndrome with insulin resistance and hypertension. These are made worse by added sugars than by salt. Appropriate diet, objective determination of individual genetic and circumstantial needs for supplementation, regular exercise, not smoking, stress management and addressing sleep disordered breathing are common sense preventive and remedial measures.

Low-normal thyroid function and cardiometabolic disorders

European Journal of Clinical InvestigationLow-normal thyroid function commonly shows up in lab results in my general practice, mostly due to the diffuse autoimmune phenomena so widespread now, but it seems to be often overlooked. A study just published in the European Journal of Clinical Investigation offers more evidence that low-normal thyroid function should be respected as a risk factor, in this case for cardiovascular and metabolic disorders. The authors state:

“Subclinical hypothyroidism may adversely affect the development of cardiovascular disease (CVD). Less is known about the role of low-normal thyroid function, that is higher thyroid-stimulating hormone and/or lower free thyroxine levels within the euthyroid [‘normal’] reference range, in the development of cardio-metabolic disorders. This review is focused on the relationship of low-normal thyroid function with CVD, plasma lipids and lipoprotein function, as well as with metabolic syndrome (MetS), chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD).”

The authors surveyed a range of reviews and meta-analyses derived from clinical and basic research papers, obtained published up to November 2014 and found:

Low-normal thyroid function could adversely affect the development of (subclinical) atherosclerotic manifestations. It is likely that low-normal thyroid function relates to modest increases in plasma total cholesterol, LDL cholesterol and triglycerides, and may convey pro-atherogenic changes in lipoprotein metabolism and in HDL function. Most available data support the concept that low-normal thyroid function is associated with MetS, insulin resistance and CKD, but not with high blood pressure. Inconsistent effects of low-normal thyroid function on NAFLD have been reported so far.”

See earlier posts for studies reporting additional adverse effects from low-normal thyroid and low-normal free T3. Practitioners should be alert to anti-thyroid antibodies indicating a pre-Hashimoto’s state and test for iodine insufficiency (by 24 hour urine collection) when indicated. The authors conclude:

“Observational studies suggest that low-normal thyroid function may be implicated in the pathogenesis of CVD. Low-normal thyroid function could also play a role in the development of MetS, insulin resistance and CKD, but the relationship with NAFLD is uncertain.”

Do higher levels of fluid intake really help the kidneys?

Summary: higher levels of fluid intake do protect against chronic kidney disease.

Chronic kidney disease (CKD) is far more common than generally known. Drinking water in excess of that demanded by thirst has been criticized as a useless effort lacking in benefit. However, a paper published in the journal Nephrology presents evidence that relatively high levels of fluid intake, up to 3.2 liters per day, does in fact protect against chronic kidney disease (CKD). The authors…

“…evaluated the association between fluid and nutrient intake and chronic kidney disease (CKD).”

They gathered data from two studies, calculating intakes of over 40 nutrients, total daily energy intake, and the total content of fluid and drinks, which they correlated to CKD as the primary outcome. What did the data show?

“Participants who had the highest quintile of fluid intake (3.2 L/day) had a significantly lower risk of CKD. These findings were consistent across both study periods, both equations to calculate GFR and both GFR thresholds.”

Increasing fluid intake beyond the amount compelled by thirst has been criticized as mythic folk medicine with no science to justify the practice. The evidence presented in this study suggests that the widespread scourge of chronic kidney disease can be reduced by higher levels of fluid intake. The authors conclude:

Higher intakes of fluid appear to protect against CKD. CKD may be preventable at a population level with low-cost increased fluid intake.

3.2 liters is 13.5 cups, a lot of water. It remains to be proven, but I suspect that somewhat lesser amounts also have benefit.

Kidney disease is another reason to prevent metabolic syndrome

Summary: the insulin receptor resistance and higher insulin levels of metabolic syndrome are a significant risk factor for kidney disease.

We’ve long known that the kidneys are exquisitely sensitive to damage from higher levels of insulin. A study recently published in the Clinical Journal of the American Society of Nephrology further reveals the contribution metabolic syndrome to chronic kidney disease. Since MetS is on the rise, chronic kidney may too. The authors state:

“Observational studies have reported an association between metabolic syndrome (MetS) and microalbuminuria or proteinuria and chronic kidney disease (CKD) with varying risk estimates. We aimed to systematically review the association between MetS, its components, and development of microalbuminuria or proteinuria and CKD.”

The authors undertook an analysis of eleven studies encompassing 30,146 subjects that reported the development of microalbuminuria or proteinuria and/or CKD in subjects with MetS, with attention to eGFR (estimated glomerular filtration rate, a metric for kidney function). Their data present a clear picture:

MetS was significantly associated with the development of eGFR <60 ml/min per 1.73 m2 [impaired kidney function]. The strength of this association seemed to increase as the number of components of MetS increased. In patients with MetS, the odds ratios for development of eGFR <60 ml/min per 1.73 m2 for individual components of MetS were: elevated blood pressure 1.61, elevated triglycerides 1.27, low HDL cholesterol 1.23, abdominal obesity 1.19, and impaired fasting glucose 1.14. Three studies reported an increased risk for development of microalbuminuria or overt proteinuria with MetS.”

The ‘take home’ message for clinicians and patients is don’t wait until the onset of type 2 diabetes; bear in mind the authors’ conclusion and take decisive action before delicate kidney tissue is irrevocably lost:

MetS and its components are associated with the development of eGFR <60 ml/min per 1.73 m2 and microalbuminuria or overt proteinuria.”

Heart rate variability analysis predicts kidney disease

Journal of the American Society of NephrologyHere’s more evidence for the profound value of heart rate variability analysis and the fundamental importance of the regulation of functions throughout the body by the autonomic nervous system. In a study just published in the Journal of the American Society of Nephrology the authors investigated the correlation between HRV and chronic kidney disease (CKD):

Autonomic imbalance, a feature of both diabetes and hypertension, may contribute to adverse cardiovascular outcomes. In animal models, sympathetic nerve activity contributes to renal damage but the extent to which autonomic dysfunction precedes the development of CKD and ESRD [end-stage renal disease] in humans is unknown.”

They measured a number of parameters of HRV analysis in a population of 13,241 adults for 16 years: and found 199 cases of ESRD and 541 patients of CKD; higher resting heart rate and lower heart rate variability was associated with both.

“Other time and frequency domain measures [of HRV] were similarly and significantly associated with ESRD and CKD-related hospitalizations. These results suggest that autonomic dysfunction may be an important risk factor for ESRD and CKD-related hospitalizations…”

It’s hard to think of a clinical test that is easier to perform yet yields more valuable information on the arousal state and capacity of the body to regulate its functions than the heart rate variability analysis.