Diabetes mellitus (“diabetes”) and hypertension, which commonly coexist, are global public health issues contributing to an enormous burden of cardiovascular disease, chronic kidney disease, and premature mortality and disability. The presence of both conditions has an amplifying effect on risk for microvascular and macrovascular complications. The prevalence of diabetes is rising worldwide ( Fig. 37.1 ). Both diabetes and hypertension disproportionately affect people in middle and low-income countries, and an estimated 70% of all cases of diabetes are found in these countries. In the United States alone, the total costs of care for diabetes and hypertension in the years 2012 and 2011 were 245 and 46 billion dollars, respectively. Therefore, there is a great potential for meaningful health and economic gains attached to prevention, detection, and intervention for diabetes and hypertension.
Epidemiology of Diabetes, Hypertension, and Diabetic Complications
The overall picture of the worldwide diabetes epidemic is sobering. In 2014, the global prevalence of diabetes was estimated to be about 9% among adults aged 18 years and older. In the U.S., diabetes is present in at least 29 million people or 9.3% of people in the population with 1.4 million Americans newly diagnosed every year. About 95% (27.5 million) of the existing and new cases are type 2 diabetes, whereas about 5% (1.5 million) of U.S. children and adults have type 1 diabetes. The prevalence of diabetes rises sharply in the obese population, and globally, 44% of diabetes cases are attributable to conditions of overweight and obesity. To put the worldwide scope of this risk in perspective, more than 1.9 billion adults 18 years and older were overweight and 600 million were obese. Diabetes is currently the seventh leading cause of death in the U.S. with World Health Organization projections that it will be seventh leading cause of death in the world by 2030.
Diabetes and hypertension commonly occur together. In a representative U.S. population during the years 2009 to 2012, overall 71% of adults with diabetes had hypertension defined by either blood pressure 140/90 or higher mm Hg or use of prescription medication to lower blood pressure. Notably, hypertension is commonly present at the time of diagnosis of type 2 diabetes. When prevalence of hypertension in type 2 diabetes is stratified by albuminuria status, 40% to 83% of patients with microalbuminuria and 78% to 96% of patients with macroalbuminuria are hypertensive. In type 1 diabetes, the prevalence of hypertension is about 30% in those without kidney disease. However, once diabetic kidney disease with albuminuria develops, hypertension prevalence parallels that seen in type 2 diabetes. People with diabetes have a shorter life expectancy with a high burden of comorbidities compared with those without diabetes. They especially are at risk for developing macrovascular (cardiovascular) and microvascular complications (kidney disease, retinopathy, and neuropathy) that are worsened by hypertension.
Among adults aged 18 years and older with a diagnosis of diabetes, compared with adults without diabetes, adjusted rates of all-cause death are 1.5 times higher. After adjusting for population age differences, the rates of cardiovascular death, and hospitalization rates for myocardial infarction, and stroke remain higher by 1.8, 1.7, and 1.5 times, respectively, compared with those without diabetes. Overall, 10% to 12% of cardiovascular deaths are attributed to diabetes. These risks are greatly amplified among the nearly 50% of people with diabetes who develop diabetic kidney disease. Indeed, most of the excess all-cause and cardiovascular death risk in diabetes is attributable to the presence of diabetic kidney disease.
Diabetic kidney disease is also the leading cause of chronic kidney disease leading to end-stage renal disease (ESRD) and currently accounts for 44% of new cases annually. Hypertension accelerates the progression of diabetic kidney disease, and kidney dysfunction further elevates blood pressure. There is an almost linear relationship between an increase in mean arterial blood pressure and yearly decrease in estimated glomerular filtration rate (eGFR). The prevalence of cardiovascular disease in patients with diabetic kidney disease increases with decreasing kidney function. The 10-year mortality rate from two large population–based cohort studies of those with eGFR 15 to 60 mL/min/1.73 m 2 , exceeds 35% in men and 20% in women. Recent data demonstrate that the increased risk of cardiovascular death starts at an eGFR of about 95 mL/min/1.73 m 2 . The National Kidney Foundation Task Force on Cardiovascular Disease in Chronic Renal Disease has recommended that people with chronic kidney disease should be considered the “highest risk group” for cardiovascular events.
In the years 2005 to 2008, 28.5% (4.2 million) of adults with diabetes aged 40 years and older had diabetic retinopathy. The coexistence of hypertensive and diabetic retinopathy further magnifies the risk of blindness. Diabetic peripheral neuropathy affects about 70% of patients with diabetes and is the leading cause of amputation in the U.S. Manifestations of autonomic diabetic neuropathy include orthostatic hypotension, decline in vasomotor tone, and lack of normal heart rate variation, resting tachycardia, and sudden death. One of the recognized risk factors for diabetic neuropathy is hypertension. The presence of autonomic neuropathy can be used for risk stratification for cardiovascular and diabetic kidney disease independent of other cardiovascular risk factors.
Pathogenesis of Diabetes, Hypertension, and Diabetic Complications
Type 2 diabetes is characterized by hyperglycemia, insulin resistance, and relative impairment in insulin secretion. Moreover, hyperglycemia itself can impair pancreatic beta-cell function (“glucose toxicity”) and reduce insulin secretion. Genetic predisposition for type 2 diabetes results from complex polygenic factors affecting numerous metabolic processes including pancreatic development and beta-cell function, insulin secretion and sensitivity, progression of glucose intolerance, metabolic rate, variability in body mass index and central fat distribution.
Obesity predisposes to insulin resistance, impaired insulin-stimulated glucose intake, and decreased sensitivity of pancreatic beta-cells to glucose. Fat itself is a source of proinflammatory mediators as reflected in high circulating levels of C-reactive protein, interleukin-6, plasminogen activator inhibitor, tumor necrosis factor, and white blood cell count. Other adipose-related factors (leptin) and increased plasma free fatty acids may promote pancreatic failure, atherosclerosis, and progressive kidney disease. Moreover, deficiency of an adipocyte derived factor, adiponectin, has been inversely associated with insulin resistance and development of diabetic kidney disease.
Diabetes, hypertension, cardiovascular, and diabetic kidney disease share common pathological mechanisms (e.g., activation of renin-angiotensin-aldosterone-system, reactive oxygen species, inflammation), which at the same time initiate and potentiate each other forming a vicious cycle of interconnected complications. Endothelial cells are essential for optimal vascular function and are at the center of diabetic complications. This cell type is especially vulnerable to injury. Endothelial dysfunction is a key initiator for atherosclerosis and thrombosis, a proximate pathway to acute events such as myocardial infarction and stroke. Through production of both endothelium–derived relaxing factors and endothelium–derived constricting factors, the endothelium modulates function of the arterial wall. The most important endothelium produced relaxing factor is nitric oxide (NO). A number of factors can lead to low NO production resulting in vasoconstriction including oxygen derived free radicals, angiotensin II, lack of exercise, high salt intake, and testosterone. In addition to down-regulation of NO release, these factors may cause endothelial cell death by apoptosis. Apoptotic cells are often replaced by dysfunctional regenerated endothelial cells that are prone to inflammation and acceleration of atherosclerosis via vasoconstrictor prostanoids (endoperoxides, prostocyclines) and endothelin-1.
In the presence of hypertension, NO production is further down-regulated by sheer stress, high salt intake, and activation of the renin-angiotensin system and aldosterone production with blunted responses to endothelium–dependent vasodilators. Endothelin-1 contributes to high vascular tone of the glomerular afferent and efferent arterioles. Prolonged vasoconstriction of these arteries produces a decrease in renal blood flow and a reduction in glomerular filtration rate associated with enhanced filtration fraction and glomerular hypertension. Endothelin-1 increases vascular reactive oxygen species (ROS) formation and is a proinflammatory and profibrotic mediator in various vascular beds.
As a result of the chronic exposure to hyperglycemia, insulin resistance, and obesity, NO phosphorylation is reduced, leading to impairment of NO–mediated relaxation in arteries of diabetic and obese patients. At the same time, production of endothelium–derived vasoconstrictor prostanoids and endothelin-1 is increased in both diabetes and obesity. Both mediators instigate vasoconstriction of vascular smooth muscle cells, which magnifies endothelial dysfunction in arteries. Adiponectin signaling which normally enhances NO generation and endothelium-dependent relaxations is impaired in obesity. A high-fat diet per se can produce similar effects.
Metabolic disturbances of diabetes initiate and sustain activation of inflammatory and injurious products and abnormal kidney hemodynamics, ultimately resulting in changes typical of diabetic kidney disease including mesangial expansion, tubulointerstitial inflammation, and kidney fibrosis ( Fig. 37.2 ). Early diabetes is characterized by glomerular hyperfiltration and hypertension, resulting in mechanical strain on the capillary walls. Afferent arteriolar resistance decreases along with relatively increased efferent arteriolar resistance, leading to increased glomerular capillary pressure and endothelial injury. Once kidney disease develops, arterial vessels have greater prevalence and severity of atherosclerotic changes with a high degree of arterial calcifications and lower collagenous fiber content. The frequency of advanced atherosclerotic lesions in carotid arteries increases progressively with lower eGFR. Calcified lesions are commonly observed in coronary arteries of patients with diabetic kidney disease ( Fig. 37.3 ).
Clinical Management of Hypertension in Diabetes
Effects of Blood Pressure Control on Diabetic Complications
The beneficial effects of blood pressure control on macrovascular and microvascular complications in diabetic patients are well recognized. The Hypertension Optimal Treatment (HOT) demonstrated improved outcomes, especially in preventing stroke, in patients assigned to lower blood pressure targets. Optimal outcomes in the HOT study were achieved in the group with a target diastolic blood pressure (DBP) of less than 80 mm Hg. The United Kingdom Prospective Diabetes Study (UKPDS 38) compared a target blood pressure of less than 150/85 mm Hg and blood pressure less than 180/105 mm Hg in newly diagnosed diabetic patients. The lower blood pressure goal demonstrated salutary effects on multiple outcomes: 24% reduced risk of predefined macrovascular and microvascular complications ( p < 0.0001); 32% risk reduction in deaths ( p = 0.019); 44% risk reduction in stroke ( p = 0.013); 37% risk reduction of microvascular complications, predominantly development of albuminuria and retinopathy ( p = 0.009). In a follow-up UKPDS study, 5102 patients from the original cohort were evaluated for the relationship between systolic blood pressure over time and risk of death and macrovascular and microvascular diabetic complications. The incidence of complications was significantly associated with systolic blood pressure: Each 10 mm Hg decrease in mean systolic blood pressure was associated with risk reduction of 12% ( p < 0.0001) for any complication related to diabetes, 11% risk reduction for myocardial infarction ( p < 0.0001), and 13% risk reduction of microvascular complications ( p < 0.0001) with no observed threshold of risk for any end point ( Fig. 37.4 ). Subsequent clinical trials including, The Appropriate Blood Pressure Control in Diabetes (ABCD-H, ABCD-N, ABCD-2V), Follow-up of Blood-Pressure Lowering and Glucose Control in Type 2 Diabetes (ADVANCE), Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) support blood pressure control to improve macrovascular and microvascular outcomes ( Table 37.1 ).
| Study | Participants | Follow-Up | Intervention | ACHIEVED MEAN BP OR BETWEEN GROUP DIFFERENCE IN TRIAL | Outcomes: Primary and Secondary | Results |
|---|---|---|---|---|---|---|
| HOT, 1997 | Subpopulation of 1501 with DM 2 and DBP 100-115 mm Hg Baseline BP 174.1/105.3 mm Hg | 3.8 years (mean) | DBP ≤ 80 mm Hgvs. DBP ≤ 85 mm Hgvs. DBP ≤ 90 mm Hg | Between group difference 3.4/2.9 | Major CV outcomes (fatal and nonfatal MI, all strokes, and all CV deaths) | ↓CV mortality Relative risk 3.0 (CI 95%, 1.28-7.08) |
| UKPDS 38, 1998 | 1148 with DM 2 and HTN (mean BP 160/94 mm Hg) | 8.4 years (median) | BP < 150/85 mm Hgvs. BP < 180/105 mm Hg | 144/82 mm Hg vs. 154/87 mm Hg | Fatal and nonfatal diabetes related endpoints, deaths related to diabetes and all-cause mortality, microvascular disease (albuminuria, retinopathy) | 24% risk reduction in diabetes related endpoints 32% risk reduction in deaths 44% risk reduction in strokes. Usual or low protein diet 37% risk reduction in microvascular endpoints (albuminuria, retinopathy) |
| ABCD-H, 1998 (hypertensive population) | 470 patients with DM 2 and DBP > 90 mm Hg | 5 years (mean) | Intensive (DBP 75 mm Hg)vs. moderate (DBP 80-89 mm Hg) | Intervention group DBP < 75 mm Hg Control group DBP < 90 mm Hg | Primary: change in CrCl Secondary: albumin excretion, LVH, retinopathy neuropathy | Significantly lower rate of MI in enalapril group over nisoldipine group in both intense and moderate BP control ( p = 0.001) |
| RENAAL, 2001 | 1513 with DM 2 and UAE >300 mg/24 hours Cr 1.3-3 | 3.4 years (mean) | Losartan vs. placebo | At the end of study BP 140/74 mm Hg vs. 142/74 mm Hg | Primary: composite of doubling of the baseline Cr, ESRD, or death. Secondary: composite of CV morbidity and mortality, proteinuria, progression of kidney disease | 16% risk reduction of primary outcome, 28% ESRD reduction, 25% reduction of doubling of Cr, 35% proteinuria reduction in losartan group. CV mortality and morbidity similar in both groups, no difference among groups of death |
| IDNT, 2001 | 1715 with DM 2 and HTN (BP > 135/85 mm Hg) Albuminuria > 900 mg/24 hours Cr 1.0-3.0 mg/dL Baseline BP 150/86.7 mm Hg | 2.6 years (median) | Irbesartan vs. amlodipine vs. placebo | Target BP < 135/85 mm Hg | Primary: composite of doubling of Cr, ESRD, or death of any cause | Irbesartan group showed: ↓20% risk of primary composite endpoint ↓30% risk of doubling the creatinine 24% slower Cr concentration increase |
| IRMA-2, 2001 | 590 with DM 2 and HTN (baseline BP 153/93 mm Hg) UAE 20-200 μ/min Cr < 1.5 mg/dL in men Cr < 1.1 mg/dL in women | 2 years (median) | Irbesartan vs. placebo | 143/83 mm Hg in 150 mg group, 141/83 mm Hg in 300 mg group, 144/83 in placebo group | Primary: developing nephropathy defined as UAE ≥ 200 μ, or UAE 30% higher than baseline. Secondary outcome: level of albuminuria, changes in CrCl, restoration of UAE < 20 μ/min | ↓UEA by 24% in 150 mg/d group, ↓UEA 38% in 300 mg/d group. Nonsignificant change in creatinine decline. Nonsignificant change in nonfatal CV outcomes |
| BENEDICT, 2004 | 1204 with DM 2 BP >130/85 mm Hg (baseline BP 150/86.7 mm Hg) UAE, 20 μ/min Cr, 1.5 mg/dL | 3.6 years (median) | Trandolapril vs. verapamil vs. trandolapril + verapamil vs. placebo | 39 ± 10/80 ± 6 mm Hg in combination group 139 ± 12/81 ± 6 mm Hg in trandolapril 141 ± 10/82 ± 6 mm Hg verapamil 142 ± 12/83 ± 6 mm Hg in placebo | Primary: onset of microalbuminuria Secondary: magnitude of treatment effect | Trandolapril + verapamil delayed albuminuria by factor 2.6. Trandalopril only delayed albuminuria by factor 2.1. |
| ABCD-N, 2002 (normotensive) | 480 participants with DM 2 and BP < 140/90 mm Hg | 5.3 years (mean) | Intensive (DBP < 10 mm Hg below baseline DBP)vs. moderate BP control (DBP 80-89 mm Hg) | BP128 ± 0.8/75 ± 0.3 mm Hg (intensive) vs. BP137 ± 0.7/81 ± 0.3 mm Hg (moderate) | Primary: Change in CrCl. Secondary: change in albumin excretion progression of retinopathy, neuropathy, incidence of CV disease | No difference in CrCl. Lower progression of albuminuria. Less progression of retinopathy, lower incidence of strokes in intensive group |
| ABCD-2V, 2006 | 129 with DM2, BP < 140/90 mm Hg (baseline BP 126/84.7 mm Hg) UAE < 30 to 300 mg/24 hours | 1.9 ± 1 year | Intensive (DBP of 75 mm Hg) vs. moderate BP control (DBP 80-90 mm Hg) | 118 ± 10.9/75 ± 5.7 mm Hg vs. 124 ± 10.9/80 ± 6.5 mm Hg ( p < 0.01) | Primary: change in UAE (prim). Secondary: changes in retinopathy, neuropathy, CV events | Significant reduction of UAE, no effect on progression of retinopathy, neuropathy, or incidence of CV events |
| ADVANCE, 2007 | 11140 with DM2 + history of major CV disease or at least one factor for CV disease Baseline BP 145/81 mm Hg | 4.3 years (mean) | Effect of routine administration of ACE inhibitor-diuretic combination on vascular events | −5.6 mm Hg SBP; −2.2 mm Hg DBP reduction in intervention group | Primary: major macrovascular and microvascular events | 9% risk reduction in macrovascular and microvascular events 18% reduction of relative risk of CV death. 14% reduction of risk of death from any cause. |
| ACCOMPLISH, 2008 | 11,464 (6924 with DM2) HTN | 35.7 and 35.6 months (3 years) | Benazepril/amlodipine vs. benazepril/HCTZ | 131.6/73.3 mm Hg (benazepril/amlodipine) 132.5/74.4 mm Hg (benazepril/HCTZ) | Primary: composite of CV death, nonfatal MI, nonfatal stroke, hospitalization for angina, coronary revascularization, resuscitation after sudden death | Absolute risk reduction of 2.2%. Relative risk reduction of 19.6% of primary outcomes in BA group |
| ACCORD BP, 2010 | 4733 with DM2 34% with previous CV disease | 4.7 years (mean) | SBP < 120 mm Hg (intensive) vs. SBP < 140 mm Hg (standard) | Primary: composite of nonfatal MI, nonfatal stroke of CV death | No significant difference between groups. Significant increase of SAE (eGFR, elevations of Cr, GFR < 30) in intensive group | |
| ROADMAP, 2011 | 4447 with DM 2 Baseline BP 136.5/80.5 mm Hg) 33% with previous CV disease | 3.2 years (median) | Olmesartan vs. placebo | Mean in − treatment 3.1/1.9 mm Hg | Primary: time to onset of microalbuminuria. Secondary: composite of CV complications and CV death | Olmesartan group: Delayed onset of microalbuminuria (23% ↑time to onset) Increased fatal CV events |
| ALTITUDE, 2012 | 8561 with DM 2 UACR > 20-200 mg/g eGFR > 30 ml/min, 60 mL/min 42% with previous CV disease Baseline BP 137.3/47.2 mm Hg | 32.9 months 2.7 years (median) | Aliskiren 300 mg vs. placebo | Mean in treatment difference in BP 1.3/0.6 mm Hg | Primary: composite of CV death or the first occurrence of cardiac arrest, nonfatal MI, nonfatal stroke, unplanned hospitalization for CHF, ESRD, death as a result of kidney failure, doubled Cr | Primary endpoints more frequent in aliskiren group. Trial stopped for safety concerns |
| VA NEPHRON, 2013 | 1448 with DM 2 UACR ≥300 mg/g eGFR 30.0-89.9 23% with CV disease Baseline BP 137/72.7 mm Hg | 2.2 years (median) | Losartan vs. losartan + lisinopril | Mean in treatment difference 1.5/1 mm Hg | Primary: First occurrence of change in eGFR, ESRD or death | Combination therapy: offers no benefit with respect to mortality of CV events. Increased risk of hyperkalemia and AKI ( p = 0.001) Trial stopped for safety concerns |
Post hoc analyses of three large clinical trials: Reduction of Endpoints in NIDDM (noninsulin-dependent diabetes mellitus) with the Angiotensin II Antagonist Losartan (RENAAL), Renoprotective Effect of the Angiotensin–Receptor Antagonist Irbesartan in Patients with Nephropathy due to Type 2 Diabetes (IDNT), and Veterans Affairs Nephropathy in Diabetes (VA NEPHRON-D) evaluated the relationship of blood pressure and kidney function. An analysis of the RENAAL trial assessed the relationship between baseline blood pressure on individual and composite outcomes including doubling of serum creatinine, ESRD, or death. Systolic blood pressure was an independent risk factor for ESRD and a baseline systolic blood pressure range of 140 to 159 mm Hg increased risk for ESRD or death by 38% ( p = 0.05) compared with blood pressure less than 130 mm Hg. In multivariate analyses, every 10 mm Hg rise in baseline systolic blood pressure increased risk of ESRD or death by 6.7% ( p = 0.007). An analysis of IDNT data showed that baseline systolic blood pressure (SBP) less than 149 mm Hg was associated with 2.2-fold increase in risk for doubling serum creatinine or ESRD compared with SBP less than 134 mm Hg. Progressive lowering of SBP to 120 mm Hg was associated with improved kidney outcomes and survival, independent of baseline kidney function. A VA-NEPHRON analysis evaluated association of mean on–treatment blood pressure with the decline in eGFR, ESRD, or death. After multivariate adjustment, the hazard of developing the endpoint became increasingly greater with a rise of SBP from more than120 mm Hg to 150 or higher mm Hg. There was significantly higher hazard ratio for SBP 140 to 149 mm Hg versus 120 to 129 mm Hg (1.51; 95% confidence interval [CI] 1.06, 2.15; p = 0.02), with a monotonic relationship between systolic blood pressure and eGFR slope suggesting that lower SBP was associated with a better outcome. However, there was also a U-shaped relationship between mean DBP and eGFR with greater loss of GFR with DBP less than 60 mm Hg. The overall conclusion of this analysis was that in patients with diabetic kidney disease characterized by high-level albuminuria, mean SBP 140 or higher mm Hg and mean DBP 80 or higher mm Hg were associated with worse kidney outcomes ( Fig. 37.5 ).
Several studies in different populations suggested that nighttime blood pressure is a strong predictor of cardiovascular events and that administration of an antihypertensive agent at bedtime resulted in lower relative risk of cardiovascular events. Another study showed that bedtime administration of antihypertensive agents resulted in significant reduction of the nighttime blood pressure and 24-hour blood pressure without change in daytime blood pressure. The American Diabetes Association Standard of Medical Care in Diabetes 2016 recommend administering at least one antihypertensive agent at bedtime.
What Is the Target Blood Pressure in Diabetic Patients?
The portion of the ACCORD trial testing an intensified blood pressure goal did not show reduced overall risk of major cardiovascular events or death. In this study of 4733 patients with established type 2 diabetes, intensive blood pressure lowering to a target less than 120/70 mm Hg failed to demonstrate benefits for fatal or nonfatal major cardiovascular events as compared with a target of less than 140/90 mm Hg. The only significant benefit in the group assigned to lower blood pressure was a reduction in incidence of stroke. Although the risk ratio was 0.58 (95% CI 0.39 to 0.88, p = 0.009), the absolute risk reduction was only 1.1%. Moreover, the lower blood pressure target was associated with a significant increase in the number of serious adverse events such as hypotension, syncope, and hypokalemia. The mean eGFR became significantly lower in the intensive-therapy group than in the standard-therapy group with significantly more instances of an eGFR less than 30 mL/min/1.73 m 2 compared with the standard-therapy group (99 versus 52 events, p < 0.001). Therefore, the results of this study raised major questions about recommendations of lower blood pressure targets, such as less than 120/70 mm Hg, for patients with diabetes. A subsequent meta-analysis of studies designed to compare clinical outcomes in people with diabetes randomized to “lower” or to “standard” diastolic blood pressure targets (ABCD-H, ABCD-N, ABCD-2V, and subgroup of HOT trial) showed nonsignificant differences in stroke (relative risk [RR] 0.67, 95% CI 0.42 to 1.05), myocardial infarction (RR 0.95, 95% CI 0.64 to 1.40), or congestive heart failure (RR 1.06, 95% CI 0.58 to 1.92) with lower blood pressure targets. Achieved blood pressure was 128/76 mm Hg versus 135/83 mm Hg ( p < 0.0001). Unfortunately, risk of ESRD and serious adverse events were not reported. A recent meta-analysis of 49 randomized clinical trials including 73,738 participants, most with type 2 diabetes, confirmed that antihypertensive treatment reduces risk of mortality and cardiovascular events in patients with a pretreatment blood pressure greater than 140/90 mm Hg treated to less than this level. In sum, the overall evidence from randomized clinical trials to date has not supported intensified blood pressure targets of less than 140/90 mm Hg for prevention of cardiovascular complications in patients with diabetes.
The Eighth Joint National Committee (JNC-8) recently published their recommendations for blood pressure targets in patients with diabetes. They recommend initiation of pharmacologic treatment at a systolic blood pressure 140 or higher mm Hg or diastolic blood pressure 90 or higher mm Hg with treatment goals less than these levels. In the general hypertensive population, including those with diabetes, initial antihypertensive treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme (ACE) inhibitor, or angiotensin receptor blocker (ARB). In African-American patients with diabetes, JNC-8 recommends initial treatment with a thiazide diuretic or CCB. The same blood pressure targets are recommended for those with chronic kidney disease irrespective of diabetes status. In diabetic patients with increased levels of albuminuria or proteinuria, the medication regimen should include an ACE inhibitor or an ARB alone or in combination with medication from other drug classes ( Table 37.2 ).
