24-h ambulatory blood pressure is linked to chromosome 18q21-22 and genetic variation of NEDD4L associates with cross-sectional and longitudinal blood pressure in Swedes.
Numerous linkage studies have indicated chromosome 18q21-22 as a locus of importance for blood pressure regulation. This locus harbors the neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) gene, which is instrumental for the regulation of the amiloride-sensitive epithelial sodium channel (ENaC). In a linkage study of 16 markers (including two single nucleotide polymorphism markers located within the NEDD4L gene) on chromosome 18 between 70-104 cM and ambulatory blood pressure (ABP), in 118 families, the strongest evidence of linkage was found for 24 h and day-time systolic ABP at the NEDD4L locus (82.25 cM) (P=0.0014). In a large population sample (n=4001), we subsequently showed that a NEDD4L gene variant (rs4149601), which by alternative splicing leads to varying expression of a functionally crucial C2 domain, was associated with diastolic blood pressure (DBP) (P=0.03) and DBP progression over time (P=0.04). A genotype combination of the rs4149601 and an intronic NEDD4L marker (rs2288774) was associated with systolic blood pressure (SBP) (P=0.01), DBP (P=0.04), and progression of both SBP (P=0.03) and DBP (P=0.05) over time. A quantitative transmission disequilibrium test in the family material of the rs4149601 supported this NEDD4L variant as being at least partially causative of the linkage result. In conclusion, our findings suggest that the chromosome 18 linkage peak at 82.25 cM is explained by genetic NEDD4L variation affecting cross-sectional and longitudinal blood pressure, possibly as a consequence of altered NEDD4L interaction with ENaC.
1999 Canadian recommendations for the management of hypertension. Task Force for the Development of the 1999 Canadian Recommendations for the Management of Hypertension.
To provide updated, evidence-based recommendations for health care professionals on the management of hypertension in adults.
For patients with hypertension, there are both lifestyle options and pharmacological therapy options that may control blood pressure. For those patients who are using pharmacological therapy, a range of antihypertensive drugs is available. The choice of a specific antihypertensive drug is dependent upon the severity of the hypertension and the presence of other cardiovascular risk factors and concurrent diseases.
The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered.
MEDLINE searches were conducted from the period of the last revision of the Canadian Recommendations for the Management of Hypertension (January 1993 to May 1998). Reference lists were scanned, experts were polled and the personal files of the authors were used to identify other studies. All relevant articles were reviewed, classified according to study design and graded according to levels of evidence.
A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension.
Harms and costs: The diagnosis and treatment of hypertension with pharmacological therapy will reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and mortality.
This document contains detailed recommendations pertaining to all aspects of the diagnosis and pharmacological therapy of hypertensive patients. With respect to diagnosis, the recommendations endorse the greater use of non-office-based measures of blood pressure control (i.e., using home blood pressure and automatic ambulatory blood pressure monitoring equipment) and greater emphasis on the identification of other cardiovascular risk factors, both in the assessment of prognosis in hypertension and in the choice of therapy. On the treatment side, lower targets for blood pressure control are advocated for some subgroups of hypertensive patients, in particular, those with diabetes and renal disease. Implicit in the recommendations for therapy is the principle that for the vast majority of hypertensive patients treated pharmacologically, practitioners should not follow a stepped-care approach. Instead, therapy should be individualized, based on consideration of concurrent diseases, both cardiovascular and noncardiovascular.
All recommendations were graded according to the strength of the evidence and the consensus of all relevant stakeholders.
The Canadian Hypertension Society and the Canadian Coalition for High Blood Pressure Prevention and Control.
Notes
Cites: CMAJ. 1999 May 4;160(9 Suppl):S7-1210333848
BACKGROUND: Treating hypertension with drugs is so far the most cost-effective way to reduce this important risk factor for cardiovascular disease (CVD). It is, however, important to determine absolute risk, and thereby estimate indication for drug treatment, in order to maintain a cost-effective drug treatment. WHO/ISH Hypertension Guidelines from 1999 propose a risk stratification for estimating absolute risk for CVD based on blood pressure and additional risk factors, target organ damage (TOD) and CVD. OBJECTIVES: We studied the consequences of applying the recent WHO/ISH risk stratification scheme to a MONICA sample of 6000 subjects from a geographically defined population in northern Sweden, regarding indications for treatment, target blood pressure and risk distribution. METHODS: We have risk-classified each of these patients using a computer program, according to the WHO/ISH scheme. Data on TOD were not available. RESULTS : In all, 917 (15%) had drug-treated hypertension. Three-quarters (n = 737) were inadequately treated, with blood pressure levels at or above 140 or 90 mmHg. 1773 (30% of 5997) untreated subjects had a blood pressure of 140/90 or above; 16% in the low-, 62% in the medium-, 8% in the high-, and 14% in the very-high-risk group. The corresponding risk-group pattern for the inadequately treated hypertensives (n = 737) was 5.5, 48.3, 11.1 and 35.2%, respectively. If we shifted the target blood pressure from below 140/90 to below 130/85 for drug-treated subjects under 60 (n = 278) the number of inadequately treated subjects increased by 34 (12.2% of 278); 14 in the low-risk group, 15 in the medium-risk group, and only five in the high- or very-high-risk groups. CONCLUSIONS: Only one-fifth of the drug-treated hypertensives were well controlled. Moreover, the incidence of newly detected blood pressure elevation was high. The majority of younger subjects with high blood pressure had low risk, but in those aged 45-54 this had already risen to a medium risk. Changing the target blood pressure to below 130/85, for subjects aged below 60, as recommended by WHO/ISH, affects predominantly low- and medium-risk groups.
The 2001 Canadian recommendations for the management of hypertension: Part one--Assessment for diagnosis, cardiovascular risk, causes and lifestyle modification.
To provide updated, evidence-based recommendations for the assessment of the diagnosis, cardiovascular risk, identifiable causes and lifestyle modifications for adults with high blood pressure.
For persons in whom a high blood pressure value is recorded, hypertension is diagnosed based on the appropriate measurement of blood pressure, the level of the blood pressure elevation and the duration of follow-up. In addition, the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases must be assessed to determine the urgency, intensity and type of treatment. For persons receiving a diagnosis of hypertension, defining the overall risk of adverse cardiovascular outcomes requires an assessment of concomitant vascular risk factors, including laboratory testing, a search for target organ damage and an assessment for modifiable causes of hypertension. Home and ambulatory blood pressure assessment and echocardiography are options for selected patients.
The outcomes were: the identification of persons at increased risk of adverse cardiovascular outcomes; the quantification of overall cardiovascular risk; and the identification of persons with potentially modifiable causes of hypertension.
Medline searches were conducted from one year before the period of the last revision of the Canadian recommendations for the management of hypertension (May 1999 to May 2001). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. Identified articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. In addition to an update of the previous year's review, new sections on assessing overall cardiovascular risk and endocrine causes are provided.
A high value was placed on the identification of persons at increased risk of cardiovascular morbidity and mortality, and of persons with identifiable causes of hypertension.
The identification of persons at higher risk of cardiovascular disease will permit counseling for lifestyle manoeuvres and introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. The identification of specific causes of hypertension may permit the use of cause-specific interventions. In certain subgroups of patients, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity or mortality.
The present document contains recommendations for the assessment of the diagnosis, cardiovascular risk, identifiable causes and lifestyle modifications for adults with high blood pressure. These include the accurate measurement of blood pressure, criteria for the diagnosis of hypertension and recommendations for follow-up, assessment of overall cardiovascular risk, routine and optional laboratory testing, assessment for renovascular and endocrine causes, home and ambulatory blood pressure monitoring, the role of echocardiography and lifestyle modifications.
All recommendations were graded according to the strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only those recommendations achieving high levels of consensus are reported. These guidelines will be updated annually.
These guidelines are endorsed by the Canadian Hypertension Society, The Canadian Coalition for High Blood Pressure Prevention and Control, The College of Family Physicians of Canada, The Heart and Stroke Foundation of Canada, The Adult Disease Division and Bureau of Cardio-Respiratory Diseases and Diabetes at the Centre for Chronic Disease Prevention and Control, Health Canada.
The 2004 Canadian Hypertension Education Program recommendations for the management of hypertension: Part I--Blood pressure measurement, diagnosis and assessment of risk.
To provide updated, evidence-based recommendations for the assessment of the diagnosis, cardiovascular risk and identifiable causes for adults with high blood pressure.
For persons in whom a high blood pressure value is recorded, the assignment of a diagnosis of hypertension is dependent on the appropriate measurement of blood pressure, the level of the blood pressure elevation and the duration of follow-up. In addition, the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases should be assessed to determine the urgency, intensity and type of treatment. For persons diagnosed as having hypertension, defining overall risk of adverse cardiovascular outcomes requires an assessment of concomitant vascular risk factors, including laboratory testing, a search for target organ damage and an assessment for modifiable causes of hypertension. Home and ambulatory blood pressure assessment and echocardiography are options for selected patients.
The identification of persons at increased risk of adverse cardiovascular outcomes; the quantification of overall cardiovascular risk; and the identification of persons with potentially modifiable causes of hypertension.
Medline searches were conducted from November 2001, one year before the period of the last revision of the Canadian recommendations for the management of hypertension, to October 2003. Reference lists were scanned, experts were polled, and the personal files of subgroup members and authors were used to identify other studies. Identified articles were reviewed and appraised using prespecified levels of evidence by content experts and methodological experts.
A high value was placed on the identification of persons at increased risk of cardiovascular morbidity and mortality, and persons with identifiable and potentially modifiable causes of hypertension.
The identification of persons at higher risk of cardiovascular disease will permit counselling for lifestyle maneuvers and introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. The identification of specific causes of hypertension may permit the use of cause-specific interventions. For certain subgroups of patients and specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality.
The document contains recommendations for blood pressure measurement, diagnosis of hypertension and assessment of cardiovascular risk for adults with high blood pressure. These include the accurate measurement of blood pressure, criteria for diagnosis of hypertension, and recommendations for follow-up, assessment of overall cardiovascular risk, routine and optional laboratory testing, assessment for renovascular and endocrine causes, home and ambulatory blood pressure monitoring, and the role of echocardiography for those with hypertension.
All recommendations were graded according to strength of evidence and voted on by the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. Only the recommendations that achieved high levels of consensus are reported. These guidelines will be updated annually.
To provide updated, evidence-based recommendations for the management of hypertension in adults.
For lifestyle and pharmacological interventions, evidence from randomized controlled trials and systematic reviews of trials was preferentially reviewed. While changes in cardiovascular morbidity and mortality were the primary outcomes of interest, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity/mortality data in this field, and for certain comorbid conditions, other relevant outcomes, such as development of proteinuria or worsening of kidney function, were considered.
MEDLINE searches were conducted from November 2003 to October 2004 to update the 2004 recommendations. Reference lists were scanned, experts were contacted, and the personal files of the subgroup members and authors were used to identify additional published studies. All relevant articles were reviewed and appraised independently, using prespecified levels of evidence, by content and methodology experts. As per previous years, only studies that had been published in the peer-reviewed literature were included; evidence from abstracts, conference presentations and unpublished personal communications was not included.
Lifestyle modifications to prevent and/or treat hypertension include the following: perform 30 min to 60 min of aerobic exercise on four to seven days of the week; maintain a healthy body weight (body mass index of 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (less than 102 cm for men and less than 88 cm for women); limit alcohol consumption to no more than 14 units per week in men or nine units per week in women; follow a reduced fat, low cholesterol diet with an adequate intake of potassium, magnesium and calcium; restrict salt intake; and consider stress management (in selected individuals). Treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and any comorbid conditions. Blood pressure should be lowered to 140/90 mmHg or less in all patients, and to 130/80 mmHg or less in those with diabetes mellitus or chronic kidney disease. Most adults with hypertension require more than one agent to achieve target blood pressures. For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic hypertension with or without systolic hypertension include beta-blockers (in those younger than 60 years), angiotensin-converting enzyme (ACE) inhibitors (except in black patients), long-acting calcium channel blockers and angiotensin receptor antagonists. Other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine calcium channel blockers and angiotensin receptor antagonists. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with diabetes mellitus, ACE inhibitors or angiotensin receptor antagonists (or thiazides in patients with diabetes mellitus without albuminuria) are appropriate first-line therapies; and in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended. All hypertensive patients should have their fasting lipids screened, and those with dyslipidemia should be treated using the thresholds, targets and agents recommended by the Canadian Hypertension Education Program Working Group on the management of dyslipidemia and the prevention of cardiovascular disease. Selected patients with hypertension, but without dyslipidemia, should also receive statin therapy and/or acetylsalicylic acid therapy.
All recommendations were graded according to the strength of the evidence and voted on by the 43 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.
2005 Canadian Hypertension Education Program recommendations. New and important aspects of the sixth annual Canadian Hypertension Education Program's recommendations for management of hypertension.
To provide updated, evidence-based recommendations for the management of hypertension in adults.
For lifestyle and pharmacological interventions, evidence from randomized, controlled trials and systematic reviews of trials was preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. For lifestyle interventions, blood pressure (BP) lowering was accepted as a primary outcome given the lack of long-term morbidity/mortality data in this field. For treatment of patients with kidney disease, the development of proteinuria or worsening of kidney function was also accepted as a clinically relevant primary outcome.
MEDLINE searches were conducted from November 2004 to October 2005 to update the 2005 recommendations. In addition, reference lists were scanned and experts were contacted to identify additional published studies. All relevant articles were reviewed and appraised independently by content and methodological experts using prespecified levels of evidence.
Lifestyle modifications to prevent and/or treat hypertension include the following: perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index of 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (less than 102 cm for men and less than 88 cm for women); limit alcohol consumption to no more than 14 standard drinks per week in men or nine standard drinks per week in women; follow a diet that is reduced in saturated fat and cholesterol and that emphasizes fruits, vegetables and low-fat dairy products; restrict salt intake; and consider stress management in selected individuals. Treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and comorbid conditions. BP should be lowered to less than 140/90 mmHg in all patients, and to less than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease (regardless of the degree of proteinuria). Most adults with hypertension require more than one agent to achieve these target BPs. For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic hypertension with or without systolic hypertension include beta-blockers (in those younger than 60 years), angiotensin-converting enzyme (ACE) inhibitors (in nonblack patients), long-acting calcium channel blockers or angiotensin receptor antagonists. Other agents for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine calcium channel blockers or angiotensin receptor antagonists. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with diabetes mellitus, ACE inhibitors or angiotensin receptor antagonists (or in patients without albuminuria, thiazides or dihydropyridine calcium channel blockers) are appropriate first-line therapies; and in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended. All hypertensive patients should have their fasting lipids screened, and those with dyslipidemia should be treated using the thresholds, targets and agents recommended by the Canadian Hypertension Education Program Working Group on the management of dyslipidemia and the prevention of cardiovascular disease. Selected patients with hypertension, but without dyslipidemia, should also receive statin therapy and/or acetylsalicylic acid therapy.
All recommendations were graded according to strength of the evidence and voted on by the 45 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.
Notes
Cites: N Engl J Med. 2000 Jan 20;342(3):145-5310639539
Cites: Lancet. 2006 Jan 21;367(9506):209; author reply 21016427487
Cites: Can J Cardiol. 2000 Sep;16(9):1094-10211021953
Cites: Can J Cardiol. 2001 May;17(5):543-5911381277
Cites: Am J Med. 2001 Nov;111(7):553-811705432
Cites: N Engl J Med. 2002 Feb 7;346(6):393-40311832527
Cites: Can J Cardiol. 2002 Jun;18(6):625-4112107420
